Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

The city of Lisbon, has any other capital of a European country, has a large number of issues while managing the waste and recycling containers spread throughout the city. This document presents the results of a study promoted by the Lisbon City Council for trialing LPWAN technology on the waste management vertical under the Lisbon Smart City initiative. Current waste management is done using GSM sensors, and the aim is to use LPWAN to reduce the costs, improve range and reduce provisioning times when changing the communications provider. After an initial study, LoRa was selected as the LPWAN of choice for the trials. The study is composed of multiple use cases at different distances, types of recycling waste containers, placements (underground and surface) and different kinds of waste level measurement LoRa sensors, deployed in order to assess the impact of the different use cases on the LoRa sensor usage. The results shown that the underground waste containers present the most difficult challenge, where the container itself imposes attenuation levels of 26dB on the link budget. The results promoted the deployment of a city wide LoRa network available to all departments inside the Lisbon City Council, and considering the network capacity the network, the network is also available to citizens to be used freely.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p<0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

The objective of this study was to review the study design and preliminary results of the Recovery trial and analyze the implementability of the Recovery trial by comparing it with the European Discovery trial.Method: The study design of the Recovery trial in the latest version of protocol was described and deeply analyzed to address the issue of implementation of the trial. A comparative analysis of study design and implementation between the UK Recovery trial and the European Discovery trial was conducted following the description.Results: The Recovery trial is a pragmatic, randomized, controlled, adaptive, open-label clinical trial. The study design of the Recovery trial was reported in the ISRCTN registry, the EU Clinical Trials Register and the U.S. National Library of Medicine ClinicalTrials.gov registry. Initially published on the 13^th March 2020, the study protocol of the Recovery trial has been updated five times at the time of this writing. More than 11,000 patients have been enrolled and 80% have completed the follow-up. Thousands of health care professionals at 175 Trusts in the UK have been involved. Conclusion: The Recovery trial applies a study design to address the issue of implementation in the context of the COVID-19 pandemic and emergency. It was conceptually pragmatic with a clear vision to address the top priority: the control of mortality and rational use of scarce resources. By contrast, the Discovery trial was designed as an intellectual exercise and consequently failed to address the issue of implementation in emergency.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

The independence of commercial law and the independence of commercial trial are the key issues in the development of China's market economy, which is of great significance for maintaining the market order and protecting the rights and interests of consumers. With the development of China's market economy, the independence of commercial law and commercial trial has gradually become the focus of social attention. On the one hand, the independence of commercial law refers to the effective distinction between commercial law as a normative system and other laws, which has an independent social and economic basis and a unique role. On the other hand, the independence of commercial trial means that commercial trial has relatively independent space and procedures, which can effectively guarantee the fair settlement of commercial disputes.The independence of commercial law is reflected in many aspects, including commercial law ontology, normative structure and content, external relations and so on. Commercial law has the independent social and economic foundation and the unique role, and is the foundation of the development of market economy. The basic principles, adjustment objects, and system design of commercial law are independent, which makes commercial law play its unique role in social life. There are differences between commercial laws and other laws, such as civil law and economic law, in essence and in expression form, which makes commercial law irreplaceable.

The main question proposed in this research is if different types of organizational approach, adapted from rapidly changing disciplines — such as IT industry, and software engineering in particular — could help overcome this gap by shortening the response time needed to analyze advanced solutions in accordance with changed circumstances, thus allowing for architectural programming to obtain different positions in the timeline of project planning and realization. We propose a novel methodology of architectural design as a self-reliant instrument inspired by Agile Manifesto and some of its instantiations, most notably by the Scrum Framework.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P <0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Introduction: Emotional intelligence plays a critical role in nursing leadership, influencing organizational dynamics and patient care. However, there is limited understanding of the impact of Emotional Intelligence on leadership in Primary Health Care in the Greek context. Methods: A longitudinal experimental design assessed the effects of an educational intervention on EI and leadership among Greek Primary Health Care nurses. Questionnaires, including the Wong and Law Emotional Intelligence Scale (WLEIS) and Multifactor Leadership Questionnaire - form 5x (MLQ), were administered pre- and post-intervention. Results: The intervention group exhibited significant improvements in Emotional Intelligence and adoption of transformational leadership styles compared to the control group. Tables highlighted nuanced changes in leadership dynamics post-intervention. Conclusions: Educational interventions effectively enhance nurses' Emotional Intelligence and influence leadership styles, emphasizing the need for tailored professional development programs in nursing education.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p<0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

Background: Schizophrenia is a mental disorder associated with inflammatory and oxidative stress markers such as lactate; in addition, the rate of physical inactivity in this population is very high, which leads to physical and metabolic alterations. Aims: This study measured the effect of assisted physical exercise over lactate levels in schizophrenia. Methods: Stable outpatients with schizophrenia and a group of Healthy controls received two different programs of Physical exercise (Aerobic and Functional) in a clinical trial. Results: Patients had higher lactate compared to healthy controls before and after intervention, and had higher rate of lactate increase after activity. The finding of increased lactate in schizophrenia detected before and after physical exercise deserve further attention in biomarker studies and in the development of physical rehabilitation in schizophrenia, suggesting different profile of oxidative metabolism after physical exercise. Basal increased lactate may reflect mitochondrial dysfunction or metabolic dysregulation, and the higher rate of increase may reflect a different metabolic and oxidative process. Conclusion: The finding is in line with recent studies as surrogate of mitochondrial dysfunction in schizophrenia and points to the need of additional studies on mitochondrial activity in schizophrenia, and to additional care in the design of physical interventions in schizophrenia.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

The study aimed to investigate the effect of climate change exposure on affect and pro-environmental behavioural intentions in a randomised controlled trial. An online survey was completed by 100 adult participants and included measures of affect and pro-environmental behavioural intentions pre- and post-exposure. Participants were randomly allocated to a group that saw a climate change video (n=55) or a group that saw a non-climate change video (n=45). The findings showed were that participants in the climate change group showed a significant increase in negative affect and pro-environmental behavioural intention scores post-video exposure compared to the non-climate change video group. This suggests that climate change video exposure negatively influences affect but also potentially increases the intention to act pro-environmentally. These findings have the potential to support policies and societal change, however further investigation into the type of contents, actual behaviour change, and impacts on diverse populations (e.g., minority groups) is needed that influences pro-environmental behaviours is required. Furthermore, to achieve a greater impact, future research should be conducted measuring actual pro-environmental behaviour change, including with those from diverse populations.

Background and objectives Osteoporotic vertebral compression fractures, particularly prevalent among the aging population, constitute a pressing global healthcare challenge. They often are unnoticed until severe pain and disability manifest, making them an underdiagnosed and undertreated condition. Patients who suffer from these fractures not only endure excruciating pain but also face diminished quality of life, impaired mobility, and the risk of respiratory compromise due to altered spinal alignment. The economic repercussions of vertebral compression fractures are substantial. Hospitalization costs, rehabilitation expenses, long-term care, and indirect costs related to lost productivity significantly burden healthcare systems and society at large , offering a promising avenue for enhancing patient outcomes and relieving the healthcare and societal financial strain posed by vertebral compression fractures. Kyphoplasty, a minimally invasive surgical technique, offers rapid pain relief, vertebral height restoration and improved function. Recognizing the importance of early intervention, this manuscript highlights the potential of kyphoplasty in mitigating both clinical and economic consequences. By addressing these fractures more effectively, kyphoplasty may potentially reduce long-term healthcare expenses and indirect costs. Material and Methods 66 randomized patients were divided into 2 treatment groups (kyphoplasty using single balloon and double balloon), analyzing radiographic and clinical parameters during 12 months of follow-up. Results Patients treated with double balloon obtained greater anterior and posterior vertebral height after reduction and a better local vertebral angle. Both groups of patients obtained clinical improvement after treatment (VAS and ODI), with no differences between the groups. Conclusion Patients treated with double balloon kyphoplasty had better radiographic results. This revision manuscript delves into the critical dimensions of these fractures, encompassing demographics, clinical consequences, challenges in diagnosis and management, and their profound economic impact. This manuscript serves to introduce an improved kyphoplasty technique to guide to the multifaceted nature of osteoporotic vertebral compression fractures and their management.

Depression and anxiety in cardiovascular disease worsen the prognosis of patients. Treatments for these disorders often provide limited improvement. The present study aimed to test, for the first time, the impact of educational technology on anxiety and depressive symptoms in patients participating in a cardiac rehabilitation program. A 12-month randomized controlled trial was conducted, in which 207 patients were randomly assigned to either the experimental (n=76) or control (n=69) groups. The intervention involved a structured patient education program provided by medical students who had undergone specially designed training in cardiac rehabilitation. The primary outcomes were death, hospitalization, heart failure, and recurrent myocardial infarction. The study also assessed anxiety and depression. A year later, the experimental group showed a statistically significant decrease in anxiety and depression on the HADS scale, with reductions of 2.0 and 1.9 points respectively (p<0.05). The control group showed reductions of 1.5 and 1.2 points (p<0.05). The difference in depression (HRDS) between the groups at 12 months was -1.29 in favor of the main group (95% CI, -0.7 to -1.88), and the standardized effect size (SMD) was 0.36 (95% CI, 0.03 to 0.69). No treatment-related adverse events were observed. The results suggest that educational interventions can have a positive impact on mental health. The study's strengths include a structured intervention, randomization, and long-term follow-up. Limitations include the lack of blinding of study participants and a relatively small sample size.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d >0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d <0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

In the context of the COVID-19 Pandemic, the use of surgical masks has become the new normal. The use of these devices in exercise and medical situations has been advocated with the purpose of reducing contagions, but some concerns exist regarding its safety. We performed maximal treadmill stress tests in 12 healthy young subjects, with and without surgical mask use, and measured exercise capacity, oxygen saturation (rest, peak exercise and post-exercise) and electrocardiographic changes. Exercise capacity and Oxygen saturation levels decreased in peak exercise vs rest in a statistically significant manner when mask was used. ECG changes, although not significant, were present in 3 subjects when mask was used and disappeared when the test was made unmasked. We conclude that masked exercise has the potential to cause decreased exercise load and oxygen saturation and potentially cause diagnostic errors in medical exams.

The present study explored the effects of a Second-generation mindfulness-based intervention known as Flow Meditation (Meditación-Fluir) in the improvement of life habits. A sample of university students (n = 51) in Spain were randomly assigned to a seven-week mindfulness treatment or a waiting list control group. Results showed that compared to the control group, individuals in the mindfulness group demonstrated significant improvements across all outcome measures, including healthy eating habits (balanced diet, intake rate, snacking between meals, decrease in consumption by emotional states negative, increased consumption by negative emotional states, amount of consumption, meal times, consumption of low-fat products), tobacco, alcohol and cannabis consumption, and resting habits. There were differences between males and females in some of these variables and a better effect of the treatment was evident in the females of the experimental group as compared to males. The Flow Meditation program shows promise for fostering healthy life habits, thus decreasing behaviors related to maladaptive eating, tobacco, alcohol and drug consumption, as well as negative resting habits, in university students. This mindfulness program can significantly contribute in the treatment of eating disorders and addictions, wherein negative emotional states and impulsivity are central features of the condition.

Abstract Psychiatric care in Spain has experienced relevant changes both in the legislative and conceptual frameworks. This new approach advocates for the combination of carrying out mental health promotion, prevention of alterations and early diagnosis and treatment, enhancing actions against stigma and emphasising the attention on the most vulnerable groups, like childhood and youth. For that, it has seen fit to perform a nursing intervention on Education and Promotion of mental health for teachers and counsellors of a secondary school located in Valencia, with the general objective of assessing their impact on stigma. Non-randomised clinical trial in which a nursing intervention on Education and Promotion of mental health was performed. Pre-intervention tools: multiple choice test validated by a group of experts; pre and post-intervention: AQ-27 (stigma attribution); in order to check its acceptance, satisfaction surveys were used. The inferential analysis included the Wilcoxon Test (pre and post AQ-27) and the Pearson Correlation Test for the quantitative variables of interest. Sample (n=22): women aged 47.96 ± 10.12 years with 18.64 ± 10.34 years of work experience. The predominant stigmatising attitude before and after intervention was “Coercion”. The ones with lower score were “Segregation” and “Anger”. The p-values obtained in the Wilcoxon Test were statistically significant (p-value <0.05) except for “pre and post Responsibility” and “pre and post Pity”. The following constructs of interest were faced: “Age” vs “Fear” (r= -0.48, moderate), “Professional experience” and “Fear” (r= -0.46, moderate) and “Help” and “Psychosis test” (r= 0.51, severe). The overall satisfaction score was 9/10. Despite the scores obtained in “Coercion” and “Psychosis”, the intervention was useful for reducing stigma in the sample.

We compared the efficacy of a tailored and a targeted intervention designed to increase clinical breast exam (CBE), mammography, and genetic services/testing among young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n=637) or the targeted (n=595) intervention. Approximately 40% of participants were Black; 12% YBCS and 27% relatives were living in more than 20 different U.S. States. Higher screening rates were reported by YBCS (CBE p=0.05; mammography p=0.04) and relatives (CBE p<0.01; mammography p=0.04) in the tailored arm, and by White/Other YBCS (CBE p=0.02) and relatives (CBE p<0.01; mammography p=0.03). YBCS genetic testing rates increased from 22% to 26% (p=0.11). Black YBCS and relatives reported higher self-efficacy and intention for genetic testing, and higher satisfaction and intervention acceptance. The tailored intervention improved CBE and mammography uptake - despite having minimal contact with participants. Professional referrals will improve genetic testing uptake. Intervention materials increased self-efficacy and satisfaction for Black women but could not overcome multiple access barriers.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p&lt;0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p&lt;0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p&lt;0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p&lt;0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol &lt;40 mg/dL in men or &lt;50 mg/dL in women (OR = 1.70); (p&lt;0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

Background: The protocol described in this paper is part of a research project coordinated 1 between three Spanish universities where a technology aimed at improving the quality of life of 2 people suffering from cerebral palsy will be developed. Part of the technology developed will consist 3 of developing an interface and a series of applications to increase motivation for daily physical activity. 4 The basis of these developments is based on the measurement of the emotional state of the subjects. 5 Methods: The experimental protocol is designed with two objectives, on the one hand to identify the 6 emotional state through physiological signals, and on the other to determine whether music can be 7 a motivating factor to promote physical activity. It has been specifically designed for subjects with 8 cerebral palsy taking into account the special characteristics of this population. These are people with 9 whom it is difficult to use questionnaires to have a basis to contrast with the measured physiological 10 signals, so measurements must be taken in carefully chosen daily life situations Discussion: As results 11 we hope to obtain which physiological parameters are the most robust to measure the emotional state 12 and how to design rehabilitation and physical activity promotion routines that are motivating, in 13 addition to being able to avoid risk factors during the performance of these routines. Trial registration: 14 NCT05621057. https://clinicaltrials.gov/ct2/show/NCT05621057

Introduction: Psoriasis is an inflammatory skin disease. The objective was to elaborate a cream with natural products and salicylic acid. Hypothesis: ¿Will the topical cream made from natural products reduce the characteristic clinical signs of psoriasis? Methodology: Quasi-experimental clinical trial, in 100 healthy volunteer subjects, five formulations of the new product were prepared and applied to each 20 healthy subjects. The universe was 270 patients with different type of dermatology disease, 120 volunteer patients were selected with Psoriasis, of which he creams was applied to 60 volunteer patients with mild and moderate psoriasis were no randomly administered the full formulation of the new product at TMC Hospital. The database for this study is in the Figshare and Dryad repository. Outcome: In healthy subjects showed that 99% had no side effects. In psoriasis patient mild and moderate psoriasis at TMC Hospital was evaluated the results before and after treatment with the new formulation, Using T Student for paired tests, in the clinical variables, as well as the PASI index and the SBA, the alternative hypothesis was proved, the new formula is effective in the control post treatment of psoriasis (p=0.000). Discussion: The new formulation showed greater efficacy after 10 days treatment. This cream is recommended as an alternative and complementary therapy for psoriasis, since it did not show secondary reactions in healthy subjects, so its effectiveness was demonstrated in this study. A new population study is recommended by regions in Ecuador: coast, highlands, Amazon and Galapagos Island, to evaluate the response to treatment.

BACKGROUND: The National Lung Screening Trial (ILST) and the NELSON study showed that lung cancer-specific mortality can be reduced by 20-24% using low-dose computed tomography (LDCT) screening in high-risk populations, due to an increase in early-stage diagnoses. RESEARCH QUESTION: How much lung cancer-related direct costs may be reduced using a LDCT screening programme based on the ILST protocol in a public healthcare system?STUDY DESIGN AND METHODS: Cost analysis of lung cancer screening (LCS) vs. usual care in the framework of the retail price of the Catalan public healthcare system. The LCS group included costs of screening (ILST protocol), treatment cost according to weighted average distribution of TNM staging in the NLST and NELSON trials, lung cancer detection rate (CDR) and smoking cessation intervention. The usual care group included treatment costs based on distribution of TNM staging registered in the Spanish index hospital. RESULTS: In the usual care group, treatment costs were €91,959. In the 5-year duration of the LCS programme, the average expected costs per subject were €1,342 (range €1,054-1,832 depending on malignancy in detected nodules) for screening and €32,431 for treatment, with an expected reduction of €952 based on an average CDR of 1.6%. The decrease in cost resulting from stage shift offsets 70.6% of the costs of the screening programme. INTERPRETATION: Baseline 5-year LCS costs are low according to the ILST protocol. In the Catalan public healthcare system, the expense reduction from the stage shift due to the LCS programme compensates a substantial part of its costs.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

This multi-center, single-blinded, randomized controlled study assessed the efficacy of phased exercise rehabilitation programs in patients who underwent a total knee arthroplasty (TKA) and investigated suitable exercise types, intensities, and frequencies for patients undergoing postoperative rehabilitation. Between January and March 2018, 494 patients who had undergone TKA were treated at two medical centers. Patients were randomized and allocated to the rehabilitation group (n=330) or the control group (n=164; treated with postoperative care). The 100-mm Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), range of motion, and Short-Form 36 (SF-36) scores were assessed and compared between the two groups. The average WOMAC score was 84.40±15.20 in the rehabilitation group and 108.30±3.90 in the control group (p=0.009). The mean VAS score was 2.54±0.16 in the rehabilitation group and 2.87±0.31 in the control group (p=0.024). Furthermore, the range of motion was 125.02±6.20 in the rehabilitation group and 116.40±1.40 in the control group (p=0.017). The mean SF-36 score was 105.40±21.50 in the rehabilitation group and 83.70±5.01 in the control group (p=0.043). This study suggests that the phase rehabilitation program could be more effective at improving pain, knee function, and quality of life than condition postoperative care after TKA.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

Objective. To evaluate serum neuronal and inflammatory biomarkers in asphyctic newborns treated with hypothermia alone or hypothermia plus melatonin, and whether biomarkers correlate with neurodevelopmental outcomes. Design. This is a pilot multicentre, randomised, controlled, double blind clinical trial. Neuronal glial fibrillary acidic protein (GFAP), granulocyte-macrophage colony-stimulating factor (GM-CSF), and inflammatory cytokines (interleukin (IL)-1, IL-2, IL-7 and IL-13) were measured in serum samples at hospital admission (T0), 24 hours (T1), 72 hours (T2) and 7-10 days of age (T3). Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales, Gross Motor Function Classification System (GMFCS) and the Tardieu scale) were performed at 6 and 18 months. Setting: Level 3 neonatal intensive care unit. Patients and interventions: 25 newborns were recruited. The treated patients received a daily dose of intravenous melatonin, 5 mg per kg body weight, for 3 days. Results. After adjusting the data for severity, in the group treated with melatonin, there is a decrease in plasma levels of GM-CSF, IL-2 and IL-13 at T1 compared to placebo, as well as, at T2, in GM-CSF concentrations, as well as IL-7 and IL-13 at T3. Evolutionarily, we found a significant decrease in GM-CSF concentrations in the treatment group compared to placebo, with no differences for the rest of the biomarkers. It is noteworthy that the sustained decrease in GM-CSF and inflammatory cytokines IL-2, IL-7 and IL-13 correlated with better neurodevelopmental outcomes at 6 and 18 months. Conclusions. In neonates with hypoxic-ischemic encephalopathy, the addition of iv melatonin to hypothermia therapy affects the plasma concentration of biomarkers in the first week of life, with a high correlation with long-term neurological prognosis.

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues, acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

To compare surgical and refractive outcomes between phacotrabeculectomy (P-Trab) and phaco with Ex-PRESS (P-Ex-PRESS) for glaucoma at 6-month follow-up. This prospective randomized controlled trial included 81 eyes; 43 (53%) and 38 (47%) were assigned to the P-Ex-PRESS and P-Trab groups, respectively. Refraction, intraocular pressure (IOP), and best-corrected visual acuity were measured. Refractive change was described by analyzing the magnitude of the cylinder, and polar analysis assessed the change in trend of astigmatism [with-the-rule, against-the-rule (ATR), oblique] evaluating mean astigmatism in centroid form. All patients showed statistically significant postsurgical decrease in IOP (P&lt;0.05). There were no differences neither between the groups for postoperative IOP or visual outcomes, nor in astigmatism before or after surgery (P=0.61, P=0.74). In both groups, the mean pre- and postoperative astigmatism was ATR and OBL, respectively. Pre- and postoperative centroids in the P-Ex-PRESS group were 0.44±1.32 D at 177˚ and 0.35±1 D at 8˚, respectively, (P=0.5) and in the P-Trab group, 0.16±1.5 D at 141˚ and 0.39±1.38 D at 29˚, respectively (P=0.38). Both P-Ex-PRESS and P-Trab showed comparable antihypertensive efficacy in treating open-angle glaucoma in a 6-month period. Pre- and postoperative astigmatism did not differ between groups. The groups showed comparable results for final visual acuity.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ), remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy (ITZ+KI) com-pared with ITZ monotherapy. Cats were randomly allocated in two treatment groups: G1 - ITZ 100 mg/cat/day and G2 - ITZ 100mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicates that clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered as the first-line treatment in the presence of negative predictors.

This investigation delves into an examination of the growth dynamics observed in Central Taiwan Science Park (CTSP) and Silicon Glen in Scotland, with a specific focus on their energy, environmental, and economic management. The aim is to predict and evaluate the latest advancements and applications of technology. In terms of energy, CTSP focuses on Taiwan's supply security and green transformation challenges, while Silicon Glen emphasizes Scotland's wind energy generation technologies. Both regions are committed to the development of renewable energy and smart grids. Regarding environmental aspects, CTSP and Silicon Glen prioritize environmental protection and sustainable development by implementing measures for environmental monitoring. In terms of economic management, CTSP, and Silicon Glen serve as key technology industry hubs This investigation delves into an examination of the growth dynamics observed in Central Tai-wan Science Park (CTSP) and Silicon Glen in Scotland, with a specific focus on their energy, environmental, and economic management. The aim is to predict and evaluate the latest advancements and applications of technology. In terms of energy, CTSP focuses on Taiwan's supply security and green transformation challenges, while Silicon Glen emphasizes Scotland's wind energy generation technologies. Both regions are committed to the development of renewable energy and smart grids. Regarding environmental aspects, CTSP and Silicon Glen prioritize environmental protection and sustainable development by implementing measures for environmental monitoring. In terms of economic management, CTSP, and Silicon Glen serve as key technology industry hubs in Taiwan and Scotland, respectively, attracting numerous high-tech and startup enterprises. Various means facilitate the growth of industries and foster innovations in different industrial spheres. Important factors contributing to this growth include policy support, availability of research materials, and provision of infrastructure. This research paper compares the successful case studies of two industrial parks, along with their environmental and economic management strategies. It explores the management principles that ensure the sustainable development and economic growth of industrial parks, aiming to assist decision-makers and relevant stakeholders in evaluating the sustainable development planning of industrial parks.

To assess the clinical efficacy of a novel organic olive oil-based denture adhesive and its effect on Candida Albicans growth in maxillary edentulous individuals wearing complete dentures. Individuals were selected from two Dental Schools in Portugal and Spain. Twenty-eight complete dentures were relined, following a standardized protocol. The novel product (Test) was compared with a commercialized adhesive (Control) and Vaseline (Placebo) randomly assigned in a cross-study design. The retention resistance was measured with a Gnathometer and a dynamometer, the patient related outcome evaluations with a 5-points questionnaire and the Candida albicans growth in a Sabouraud dextrose agar (SDA) medium in order to evaluate differences between the placebo and experimental product. Twenty-three participants were included. Dynamometer evaluation showed significant differences between not using a denture adhesive and using either (experimental, p = .03; control, p = .04), no significant differences between the two adhesives (p &gt; .05). In the subjective analysis, the experimental adhesive showed a significantly longer effectiveness (p = .001); the control reported better results at taste (p = .03) in chewing (p = .001). The test adhesive showed better (p &lt; .001) Candida albicans growth inhibition. The experimental adhesive showed longer effectiveness than the control and placebo with a better inhibition capacity for the growth of Candida albicans, patients reported better abilities for speech, chewing, taste and retirement in the control adhesive.

Background Posttraumatic stress disorder (PTSD) is a complex condition that represents a significant burden in terms of individual disability and societal costs. Despite decades of research investigating treatment options, PTSD remains a major cause of quality-of-life impairment. We hypothesized that patients with PTSD might benefit from peripheral somatosensory stimulation (PSS) therapy. Methods Six adult patients with clinically diagnosed PTSD were enrolled to undergo daily PSS therapy over a 4-week period. Patients completed two surveys evaluating satisfaction with treatment and overall well-being (Survey 1) and severity of PTSD symptoms (Survey 2). Survey 1 was completed weekly during the course of the study. Survey 2 was based on the 9-question National Stressful Events Survey PTSD Short Scale (NSESSS) and was completed as a baseline prior to initiation of therapy and then at the conclusion of the trial. All data were analyzed by an independent statistician. Results Six male patients were enrolled in the study; all completed the trial. All patients demonstrated a decrease in symptoms within one week of initiation of therapy. This benefit was sustained and appeared to further improve over the course of the trial. For Survey 1, the overall median scores demonstrated a significant time-dependent improvement across measurement times (p < 0.001). For Survey 2, patients had statistically significant improvements from baseline regarding feelings of being emotionally upset and being overly alert. Results from a cumulative link mixed model demonstrated that treatment yielded a 38.2-fold higher likelihood of transitioning from a higher PTSD score at baseline to a lower (improved) score at week 4. No adverse events were described by the patients. Conclusions PSS stimulation appeared to improve symptoms in all six patients with PTSD symptoms in this trial. Patients had unanimous and clinically meaningful improvement in overall PTSD symptoms with treatment. By week 4, all patients responded that they enjoyed the treatment and would like to keep their device. We suggest that further investigation into the potential usefulness of PSS therapy in patients with PTSD is warranted.

A single paragraph of about 200 words maximum. Electroencephalography (EEG) accumulates the electrical activities of human brain. It is an easy and cost effective tool to characterize motor imagery (MI) task used in brain computer interface (BCI) implementation. The MI task is represented by short time trial of multichannel EEG. In this paper, the raw EEG is decomposed into a finite set of narrowband signals obtained from individual EEG channels using Fourier transformation based bandpass filter. Each of the subband signals represents narrowband rhythmic components which characterize the brain activities related to motor imagery. The subband signals are arranged to extent the dimension of EEG trial in spatial domain. The spatial features are extracted from the set of extended trials using common spatial pattern (CSP). An optimum number of features are used to classify the motor imagery tasks represented by EEG trials. Artificial neural network is used to classify MI tasks. The performance of the proposed method is evaluated using two publicly available benchmark datasets. The experimental results show that it performs better than the recently developed algorithms.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

The study's objective was to assess the impact of Mediterranean diet/lifestyle interventions for weight loss on Positive airway pressure (PAP) adherence, Body mass index (ΒΜΙ), sleepiness, and blood pressure measurements (BP) in patients with obstructive sleep apnea (OSA). We designed a randomized, controlled trial, including overweight and obese patients with moderate-to-severe OSA, randomized to standard care (SCG, n=37) and Mediterranean diet group (MDG, n=37). SCG received healthy lifestyle advice, while MDG underwent a 6-month behavioral intervention aiming to enhance weight loss and adherence to Mediterranean diet. PAP adherence, BMI, Epworth Sleepiness Scale (ESS) and BP measurements were evaluated pre- and post-intervention. Post-intervention PAP use was higher in MDG compared to SCG (6.1 vs 5.4, p=0.02). Diet/lifestyle intervention was one of the most significant predictive factors for PAP adherence (OR = 5.458, 95% CI = 1.144-26.036, p=0.03). The SCG demonstrated a rise in BMI, while the MDG displayed a decline (0.41 vs -0.75, p=0.02). The MDG also demonstrated a substantial reduction in adjusted SBP (-5.5 vs 2.8, p=0.014) and DBP (-4.0 vs 2.5, p=0.01). Ultimately, incorporating a dietary/lifestyle intervention with standard care yields superior PAP adherence, BMI, and BP measurements in contrast to standard care alone, underscoring the potential benefits of allocating increased time and support within the MDG group. Trial registry: ClinicalTrials.gov; No.: NCT05881824; URL: www.clinicaltrials.gov.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Despite the recommendation to treat depression using the transcranial direct current stimulation (tDCS), novel findings raised doubts over the tDCS efficacy in managing depressive episodes. Neurophysiologic approaches to understand the specificities of brain responses to tDCS in de-pressed patients remains a feature. Objective: to compare the immediate hemodynamic responses to tDCS on left dorsolateral pre-frontal cortex (DLPFC; F3-Fp2 montage) in patients with depres-sive disorder and healthy controls (no additional stimuli). Methods: Sixteen participants were al-located in depression group and 16 in the control group. Both groups received 2mA tDCS for 20 minutes, using the F3-Fp2 montage. The hemodynamic effect over the DLPFC was assessed using near-infrared intracranial spectroscopy (NIRS) positioned on the left supraorbital region (Fp1). Mean, minimal and maximal values of baseline and post-stimulation rates of oxygen saturation (SatO2) were recorded. The oxygenated hemoglobin rates (HbO) were extracted. Results: Be-tween-group differences were detected for mean and minimal baseline rates of SatO2 and HbO levels. The depression group showed lower results compared to the control group. After the pro-tocol, only the depression group showed increased mean and minimal rates of SatO2 and HbO. The post-tDCS rates were equal for both groups. Conclusion: The findings showed immediate anodal tDCS effects over DLPFC hemodynamics. The effects were exclusive for the lowest base-line rates group, not affecting the normal oxygen rates group. The minimal increase of SatO2 and HbO rates after the protocol in the depression group suggests that those with reduced cerebral perfusion may be more affected by tDCS.

In this pilot study, 84 subjects with a history of poor oral hygiene were enrolled in an interventional, randomized, prospective, open-label controlled trial. The aim was to provide preliminary clinical data on the products, the recruitment monthly rate, and patient satisfaction to estimate resources for the main study, as well as descriptive data on oral microbiota rebalancing. The population was divided into five groups: 20 participants received delicate mint toothpaste, 12 mint toothpaste, 20 mint mouthwash, and 20 delicate mint toothpaste and mint mouthwash using a specifically custom-designed toothbrush. The 12 subjects in the control group continued to use their oral care products without changing their normal routine. The study duration was 28 days.All subjects tolerated the products well, and there were no adverse events. Recruitment capability and procedures allowed a realistic estimation for the future main trial. The products did not cause any changes in tooth color. The participants who completed the treatment consisting of delicate mint toothpaste, mint mouthwash, and the specifically custom-designed toothbrush showed the gingival sensitivity best results (p≤0.000). The products induced a statistically significant decrease in plaque in all treated groups (p≤0.000) and an improvement of gingival sensitivity (delicate mint toothpaste, p≤0.005; mint toothpaste, p≤0.015; and mint mouthwash, p≤0.015). All the products were effective in stabilizing the oral microbiota.The tested products showed an optimal safety profile. They also stabilized the biodiversity of the oral microbiota, making it less susceptible to microbial fluctuations than the control group.

Background: This study aimed to develop and evaluate a dietary self-care promotion program for hemodialysis patients based on Hurley's self-efficacy model. Methods: The needs of hemodialysis patients were identified, and an online community-based dietary self-care promotion program was developed with expert evaluations. 44 hemodialysis patients were randomly assigned to an experimental group (n=22) and a control group (n=22). The program was applied to the experimental group for four weeks. Before and after the intervention, as well as four weeks after the intervention, dietary self-efficacy, dietary self-care behavior, interdialytic weight gain, serum phosphorus, and serum potassium were assessed in both groups. Results: Significant differences over time and between groups were observed in dietary self-efficacy, interdialytic weight gain, serum phosphorus, and serum potassium. The interaction between time and group was also significant. While no significant differences were found over time in dietary self-care behavior, significant group differences and interaction effects between time and group were identified. Conclusions: The results indicate that the dietary self-care promotion program using an online community for hemodialysis patients is more effective in enhancing dietary self-efficacy and dietary self-care behavior compared to conventional treatment. This suggests the clinical applicability of the proposed dietary self-care promotion program.

Background: Two types of medicinal systems are available in Korea: Western and oriental. These exist as separate services that independently provide medical care to patients. We determined the utility and benefits of compressive and integrated medical services (CIMS) comprising 12 sessions of acupuncture and healing programs over 6 weeks. Methods: In this two-group parallel single-center randomized controlled assessor-blinded trial, 24 participants were assigned to either the experimental (conventional medical treatment plus CIMS, n = 12) or control (conventional medical treatment, n = 13) group. Spinal nerve root block was performed on the compressed spinal nerve root (identified using magnetic resonance imaging) when no improvement was observed after the initial treatment. The experimental group received 12 cycles of acupuncture and manual therapy for 6 weeks; the control group received conventional medical treatment alone. Results: The average age of participants in the experimental and control groups was 70.73 ± 5.95 and 67.33 ± 8.89 years, respectively. There were no significant differences between the groups in terms of age, body mass index, Leeds Assessment of Neuropathic Symptoms and Signs, sex, and current medical history. We found high compliance for both programs (acupuncture and healing). On exclusion of between-group effects, the visual analog scale (VAS) score improved significantly over time (p = 0.045). Further, comparison of the groups after excluding the effects of visits revealed significantly lower VAS scores in the experimental group than in the control group (p = 0.000). Conclusions: Patients with degenerative lumbar spinal stenosis who mainly complain of radiating pain in the lower leg may benefit from CIMS after spinal nerve root block for ≤3 months after treatment. Our study findings suggest that this treatment improves spinal function and Oswestry Disability Index score. However, CIMS did not improve QoL.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double-blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and acceptability of the intervention in preparation for a future 8-week RCT which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n=10) and non-depressed (n=6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to diet allocation and study hypotheses. Health questionnaires were completed before and after the intervention, and, throughout the study, questionnaires assessed ratings of liking and sensory properties of the meals, adherence, and open-ended feedback. In the ND group, 75% of participants consumed no non-study foods, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

The purpose of this study is to explore the effects of dual-task training, including cognitive tasks, on cognitive and bodily functioning and β-amyloid levels in Alzheimer's dementia patients. The subjects were 34 inpatients diagnosed with Alzheimer's dementia at a nursing hospital located in Gyeongsansi, South Korea. The patients were randomly divided into a dual-task group (n = 16) and a single-task group (n = 18). The dual-task group performed cognitive tasks at the same time as exercising tasks, while the single-task group performed only exercise tasks. Each group was trained for 30 minutes three times a week for eight weeks. The Mini-Mental State Examination was used to measure the patients’ cognitive function. Static and dynamic balance were measured to evaluate bodily functioning. Static balance was measured using Biorescue, while dynamic balance was measured using the Berg Balance Scale. Blood analysis was performed to measure levels of β-amyloid, which is known to cause Alzheimer's dementia. Both groups exhibited statistically significant improvements in gait function after the training (p < .05). The dual-task group exhibited statistically significant differences in cognitive function, static and dynamic balance function, and β-amyloid levels after training (p < .05). A significant difference was observed between the two groups (p < .05). Dual-task activities were found to be effective in improving cognitive and bodily functioning and reducing β-amyloid levels in Alzheimer's dementia patients. Therefore, dual-task training is thought to be an effective method of treating and preventing Alzheimer's dementia.

A 24 week-controlled trial was conducted in menopausal women (mean age:61.5) to assess serum 25-hydroyvitaminD (s25OHD) evolution in relation to three interdependent determinants: doses of supplemented (Suppl.) vitamin D₃ (VitD₃); baseline status; seasonality. Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time-controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125 g servings of VitD₃-fortified yogurts with 5 and 10 µg daily doses, respectively. The 16 intervention-weeks lasted from early-January to mid-August, the 8 follow-up-weeks from late-August to mid-October. Before enrollment, subjects were randomized into two s25OHD strata: “Low stratum (LoStr)“: 25-50 nmol/L; “High stratum (HiStr)“: >50-75 nmol/L. All enrolled participants remained compliant until study end: Gr.Suppl.0 (n=45), Gr.Suppl.5 (n=44) Gr.Suppl.10 (n=44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than Gr.Suppl.5. The constant rate of s25OHD per supplemental VitD₃ microgram was greater in LoStr than HiStr. s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. In conclusion, this randomized trial demonstrates: -a dose-dependent s25OHD improvement related to fortified yogurt consumption; -an inversely baseline-dependent increase in s25OHD; -a seasonal effect that highlights the importance of vitamin D₃ supplementation during winter, even at 5µg/d, in healthy menopausal women.

Objectives. To show the superiority of eccentric versus concentric strengthening in terms of improving quadriceps strength in knee osteoarthritis (OA). A randomized controlled study was conducted to perform 12 sessions of either eccentric or concentric isokinetic muscle strengthening over 6 weeks Methods. We recruited males and females, aged between 40 and 70 years, with predominantly unilateral femorotibial OA. Exclusion criteria were having a prosthesis, inflammatory arthritis or flare-up of OA, symptomatic patellofemoral OA, cardio-vascular or pulmonary disease that could be a contraindication to the study treatment, and any pathology that could cause muscle weakness. The primary endpoint was the between-group difference in change in maximum concentric isokinetic knee extension peak torque (PT) at 60°/s on the OA side at 6 weeks. Secondary endpoints were between-group difference in change in concentric hamstring PT at 60°/s; eccentric quadriceps and hamstring PT at 30°/s; 10 m and 200 m walking speeds; pain and functional status (WOMAC score) at 6 weeks and 6 months. Results. The sample consisted of 11 females and 27 males, with a mean age of 57.7 ±7.52 years and a body mass index (BMI) of 25.95 ±3.93 kg/m². Quadriceps strength increased more at 6 weeks in the concentric than the eccentric group with no statistical difference. There was a rate of 25% major adverse events in the eccentric group. Conclusion. Eccentric training resulted in a smaller improvement in quadriceps strength than concentric training and was associated with a high risk of muscle injury, particularly to the hamstring muscles.

The aim of this randomized controlled clinical trial was to compare the 2-year clinical performance of resin composite restorations placed at non-caries cervical lesions (NCCL) with one-step self-etch, total-etch, and selective enamel etch & self-etch adhesive techniques. Thirty-two patients received three resin composite restorations each at NCCLs (Tetric EvoCeram/Ivoclar/Vivadent), bonded with a total-etch adhesive agent (ExciTE F/Ivoclar/Vivadent) and a self-etch (AdheSE One F/Ivoclar/Vivadent) without and with selective enamel etching. All restorations were evaluated by two examiners at baseline, 6-, 12-, 18- and 24-months post-operation regarding retention, caries occurrence, marginal adaptation, and marginal staining. A logistic regression analysis with generalized estimating equations was used. After 2 years, the retention rate was 86,8% for total-etch, 92.26% for self-etch, and 93.63% for selective enamel etching & self-etch. No caries were detected during all the restorations. Concerning marginal adaptation, the clinically perfect restorations were 26.9% for the total-etch technique, 16% for self-etch, and 25,9% for selective enamel etch & self-etch. All three adhesive strategies provided restorations with no significant differences in the retention rate and the marginal adaptation, whereas the total etch yielded better performance for marginal staining. All the restorations were assessed as clinically acceptable after 2 years.

BACKGROUND: We investigated whether immigrants from Southeast Europe (SE) and Swiss patients have different reasons for visiting the emergency department (ED). METHODS: Our retrospective data analysis for the years 2013-2017 describes the pattern of ED consultations for immigrants from SE living in Switzerland (Canton Bern), in comparison with Swiss nationals, with a focus on type of referral and reason for admission. RESULTS: A total of 153,320 Swiss citizens and 12,852 immigrants from SE were included in the study. The mean age was 51.30 (SD=21.13) years for the Swiss patients and 39.70 (SD=15.87) years for the SE patients. For some countries of origin (Albania, Bosnia and Herzegovina, and Turkey), there were highly statistically significant differences in sex distribution with the predominance for male. SE immigrants had a greater proportion of patients in the lower triage level (level 3: SE: 67.3% vs. Swiss: 56.0%) and a greater proportion of patients in the high triage level than the Swiss population (level 1: SE: 3.4% vs. Swiss: 8.8%,). SE patients of working age (16-65 years) were six times more often admitted by ambulance than older (≥65 years) SE patients, whereas in the Swiss population this ratio was similar. In both groups, fast track service was primarily used for patients of working age (<65) and more than three times more often in the SE than the Swiss group (SE: 39.1%, Swiss: 12.6%). CONCLUSION: We identified some indications in access to primary care in Emergency Department for immigrants highlighting the need for attention to the role of organizational characteristics of primary health care in the Switzerland. The authors have highlighted the need for professional support to improve the quality of healthcare for immigrants. In the future, more primary care services and general practitioners will need to be provided with a migrant background.

Traditionally it has been thought necessary to lose 2% of body mass due to dehydration, before functioning is disrupted, although recently adverse effects have been reported with a loss of 0.5-0.7%. It is, however, unclear whether the response to small decreases in mass reflects dehydration, mechanisms that help to adapt to a loss of bodily fluid, or a placebo effect. Individuals were therefore subject to a temperature of 30°C for three hours, and mood and cognition monitored. To explore the possibility of a placebo response, the consumption of plain or coloured water was compared. To consider changes in hydration status, drinks known to differ in their ability to rehydrate were contrasted. Not drinking was disruptive, although a combination of plain water and electrolyte’s most effectively prevented a decline in functioning, indicating a role for rehydration after a loss of 0.52% body mass. There was, however, also evidence of a placebo response: a combination of plain water and electrolytes was better able to prevent a decline in functioning than coloured plain water and electrolytes. As increased anxiety was a robust response, it was discussed whether the renin–angiotensin–aldosterone system might be part of the mechanism.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Objective To investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. Design A single- center pilot trial Setting Faculty of Health, Tsukuba University of Technology, Japan Participants hypertensive community-dwelling elderly people Intervention Microcirculation was observed before and 1 min after arm-curl exercise by means microscopy of capillary with non-exercised limb. Additionally, we examined other health-related indicators. Outcome measures: Acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters.　 Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3±6.7 to 2.7±0.2 log µm/s (P

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Executive functioning is a key component involved in many of the processes necessary for effective weight management behavior change (e.g., setting goals). Cognitive behavioral therapy (CBT) and third-wave CBT (e.g., mindfulness) are considered first-line treatments for obesity, but it is unknown to what extent they can improve or sustain executive functioning. This pilot randomized controlled trial examined if a CBT-based generalized weight management intervention would affect executive functioning and executive function-related brain activity in individuals with obesity or overweight. Participants were randomized to an intervention condition (N=24) that received the Noom Weight program or to a control group (N=26) receiving weekly educational newsletters. EEG measurements were taken during Flanker, Stroop, and N-back tasks at baseline and months 1 through 4. After 4 months, the intervention condition evidenced greater accuracy over time and, to some extent, neural markers of executive function (error-related negativity and beta and gamma band powers) compared to the control group on the Flanker and Stroop tasks. The intervention condition also lost more weight than controls (-7.1 pounds vs. +1.0 pounds). Given mixed evidence on whether CBT-based interventions can change markers of executive function, this study contributes preliminary evidence that a multicomponent CBT-based weight management intervention (i.e., that provide both support for weight management and is based on CBT) can help individuals sustain executive function compared to controls.

Severe postoperative pain affects most patients after thoracotomy and is a risk factor for post-thoracotomy pain syndrome (PTPS). This randomized controlled trial compared preemptively administered ketamine versus paravertebral block (PVB) versus control in patients undergoing posterolateral thoracotomy. The primary outcome was acute pain intensity on the visual analog scale (VAS) on the first postoperative day. Secondary outcomes included morphine consumption, patient satisfaction, and PTPS assessment with Neuropathic Pain Syndrome Inventory (NPSI). Acute pain intensity was significantly lower with PVB compared to other groups at four out of six time points. Patients in the PVB group used significantly less morphine via a patient-controlled analgesia pump than participants in other groups. Moreover, patients were more satisfied with postoperative pain management after PVB. PVB, but not ketamine, decreased PTPS intensity at 1, 3, and 6 months after posterolateral thoracotomy. Acute pain intensity at hour 8 and PTPS intensity at month 3 correlated positively with PTPS at month 6. Bodyweight was negatively associated with chronic pain at month 6. Thus, PVB but not preemptively administered ketamine decreases both acute and chronic pain intensity following posterolateral thoracotomies. The trial was prospectively registered at the Australian New Zealand Clinical Trial Registry (https://www.anzctr.org.au/; ACTRN12616000900415; 07 July 2016).

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

This pilot randomized controlled trial (RCT) aimed to explore whether depression and anxiety could be reduced by psychiatric home healthcare supporters offering brief cognitive behavioral therapy for psychosis (CBTp) at home using a workbook for patients with schizophrenia. Eighteen patients with schizophrenia treated in a psychiatric home nursing service were randomly assigned to two groups: one group received CBTp in addition to usual care (CBTp + TAU group; n=8) and the other received only usual care (TAU group; n=8); 2 patients were excluded due to hospitalization or withdrawal of consent. Eight weekly CBTp sessions were conducted; anxiety/depression, quality of life, self-esteem, and overall functioning were assessed at baseline, week 9, and week 13. There was no significant difference in the primary evaluation; however, a significant improvement (p=0.014) was observed in the secondary evaluation of quality of life. The effect size was 0.95 for primary evaluation and 1.33 for the secondary evaluation, indicating a large effect. This study showed that nurses and occupational therapists can provide CBTp in psychiatric home care for patients with schizophrenia to potentially alleviate anxiety and depression compared to standard psychiatric home care alone. Therefore, larger RCTs with larger sample sizes are recommended.

The increasing number of caesarean section (CS) is a major challenge in modern obstetrics. This rise is not supported by better neonatal and maternal outcomes. The prevention of unnecessary primary CS is a global priority. This study focuses on effectiveness and safety of yoga practice during pregnancy and it’s connection to perinatal outcome. We conducted a single-blinded, randomized controlled clinical trial, with healthy singleton primiparas, randomized at first trimester of pregnancy. A total of 214 participants were randomized, 106 in yoga and 108 in controls. The study group performed yoga exercise while the controls received standard antenatal care. The yoga exercises were performed once a week, lasted 90 minutes, under the supervision of a certified yoga teacher. All pregnant women from study group completed 12 yoga exercises. The results showed that the yoga group had a lower rate of urgent intrapartum CS (p-0.004) and more frequent spontaneous vaginal delivery (p-0.009), while the control group had a higher rate of induced labour (p-0.032). Conclusion: Yoga practice in pregnancy is a promising intervention that has a potential to decrease intrapartum urgent CS rates and assures natural and spontaneous vaginal birth; it’s highly recommendable to healthy pregnant women.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Eating Disorders (ED) constitute a serious public health issue affecting predominantly women and appearing typically in adolescence or early adulthood. EDs are extremely difficult to treat as these disorders are ego-syntonic and many patients do not seek treatment. It is vital to focus on the development of successful early-intervention programs for individuals presenting at-risk and are on a trajectory towards developing EDs. This study is a randomized controlled trial evalu-ating an innovative digital gamified Acceptance and Commitment early-intervention program (AcceptME) for young females showing signs and symptoms of an ED and at high-risk for an ED. Participants (N=92; Mage=15.30 years, SD=2.15) received either AcceptME (N=62) or a waitlist control (N=30). Analyses indicated that the AcceptME program effectively reduced weight and shape concerns, with large effects when compared to waitlist controls. Most participants scored below the at-risk cut-off (WCS score<52) in the AcceptME at end-of-intervention (57.1%) com-pared to controls (7.1%) with odds of falling into the at-risk group being 14.5 times higher for participants in the control group. At follow-up, 72% of completers reported scores below the at-risk cut-off in the AcceptME group. The intervention also resulted in a decrease in ED symp-tomatology and increased body image flexibility. Overall, results suggest that the AcceptME program holds promise for early-intervention of young women at-risk for developing an ED.

Anemonia viridis is an abundant and widely-distributed temperate sea anemone that can form dense congregations of individuals. Despite the potential severity of its sting, few detailed cases have been reported. We report a case of a severe toxic reaction following an A. viridis sting in a 35-year-old oceanographer. She developed severe pain, itching, redness and burning sensation, which worsened one week after treatment with anti-inflammatories, antihistamines and corticosteroids. Prompted by this event, and due to the insufficient risk prevention, lack of training for marine-environment users and lack of research into sting-specific first-aid protocols, we evaluated the cnidocyst response to five different compounds commonly recommended as rinse solutions in first-aid protocols (seawater, vinegar, ammonia, baking soda and freshwater) by means of the Tentacle Solution Assay. Vinegar and ammonia triggered an immediate and massive cnidocyst discharge after their application and were classified as activator solutions. Baking soda and freshwater were also classified as activator solutions, although with a lower intensity of discharge. Only seawater was classified as a neutral solution and therefore recommended as a rinse solution after A. viridis sting, at least until an inhibitory solution is discovered.

Background and Objectives: Blood flow restriction (BFR) has been investigated as an alternative method combined with resistance training or AT to promote different health benefits for older people. Nevertheless, no study analyzed chronic effects of BFR on muscle activation in this population, and in some investigations, the application of BFR has been employed arbitrary pressures, which can be a serious methodological error, both from the results and of the risk to the health of the older. Thus, this study analyzed the effect of 24 weeks of walking with BFR on activation and muscle strength in elderly women with osteoporosis. Materials and Methods: Thirty older women (66.0±4.6 years) performed randomly to one of three training groups: WALK (moderate-intensity walking), WALK+BFR (low-intensity walking with BFR), or BFR (BFR alone). Muscle activation (sEMG) and strength of knee flexors and extensors were measured pre-intervention and after 12 and 24 weeks. Results: Only a trivial effect size (ES) for the WALK+BFR (ES= 0.16) was observed in sEMG of the knee flexors compared to WALK. A moderate effect was observed in sEMG of the knee extensors (ES= 0.65) for the WALK+BFR compared to the WALK. However, adverse effects were found in the strength of the knee flexors for the BFR (ES= −0.86) and WALK+BFR (ES= −0.69) compared to WALK. Adverse and null effects, respectively for the BFR (ES= −0.16) and WALK+BFR (ES= 0.06) groups, were also observed on the strength gain of the knee extensors. Conclusions: Low-intensity walk combined with BFR does not provide relevant chronic effects on strength gain or even limit muscle strength gain, however, due to greater activation of knee extensors over 24 weeks, it is possible to benefit from the use of similar strategies to obtain neuromuscular gains in the long‐term for elderly women with osteopenia and osteoporosis.

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, cross-over, pilot clinical trial examined 13 patients with chronic kidney disease (CKD). Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and serum albumin, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23. Consequently, this dietary supplement may prevent cardiovascular events in patients with CKD.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. 2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension undergoing treatment with ACE inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive susbtances, were also quantified before and after the treatment period. 3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. 4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n=103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Pre-medication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1-2 HSR to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3-4 HSR to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSR in gynecologic cancer. Our study showed that HSR in gynecologic cancer is common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSR in gynecologic cancer was highlighted.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a posthoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, taper/stop) as the predictor. 282 patients were analysed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small and related to relapses but to on overall functional decline.

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.