Dysmenorrhea symptoms are frequent and often self-treated using non-prescription medicines. To further characterize women with dysmenorrhea using a combination of hyoscine butylbromide and paracetamol (PLUS) for self-management of their complaints, we performed a secondary analysis of a published pharmacy-based patient survey. 314 women (mean age 32.3 years) with dysmenorrhea reported a pain and cramps intensity of 7.45 ± 2.13 on a 0-10 Likert scale, which was reduced to 2.86 ± 1.81 upon treatment. Associated impairments of work/daily chores, leisure activities, and sleep were improved by 64.6%, 62.2% and 70.4%, respectively. The onset of symptom relief was within 60 min in 84.7%. Tolerability was rated as very good or good by 97.2%. These findings confirm the efficacy and tolerability data on PLUS from randomized controlled trials in a larger group of women conducting self-management of their dysmenorrhea.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity < 80%, but both values > 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

The One Health approach often reaches classrooms through Environmental Education (EE), which aims to guide society's response to current crises (environmental, health, economic, values). However, traditional EE teaching has focused on isolated ecological concepts and standardized solutions, ignoring the multidimensional nature of EE and failing to integrate the interdependence between environmental, animal, and human health. Moreover, teacher training often neglects didactic content knowledge, preventing students from acquiring the systemic vision needed to address eco-social problems and create sustainable solutions aligned with the Sustainable Development Goals (SDGs). This limits teachers’ ability to influence students' concerns and behaviours. In this context, this study aims to reflect on the current state of the issue and propose strategies informed by Science Education research to improve EE teaching, enabling the integration of One Health dimensions through effective didactics to achieve Transformative Environmental Education (TEE). For this purpose, we begin by addressing the limitations identified in recent systematic reviews, shifting the paradigm towards a symbiosis of EE and Science Education through scientific practices. We then present practical examples showcasing successful EE initiatives that foster a deeper understanding of socio-environmental issues, encourage innovative solutions, and nurture engaged citizens from early education onwards. These proposals can support classroom practice and ongoing teacher self-development. Pedagogical strategies include tackling issues that require systemic and critical thinking by developing scientific and epistemic practices while raising awareness of environmental justice. Thus, this study advocates for a new vision of EE, integrating the One Health approach, which could be applied to develop new educational programs, including teacher training. This would lead to a new learning evaluation model and help identify key determinants that trigger pro-environmental behaviours.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Objective: Subclinical left ventricular disfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). Many patients with diabetes have an impaired diastolic and systolic function. With preserved ejection fraction LV (EFLV), the latter is defined as reduced global longitudinal strain (GLS), detected using the speckle-tracking echocardiography. This study is aimed to define the long-term structural and functional disorders of the LV myocardium in patients with T2D without CVD. Methods: Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11±7.9 years), included in the study in 2012-2013, only 57 responded to the follow-up study. The patients were divided into two groups: one with T2D (n=29), the other without it, control (n=28). All patients underwent transthoracic two-dimensional echocardiography with assessment of standard indicators of systolic and diastolic cardiac function, as well as GLS. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. Results: During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) in the type 2 diabetes group was found from 53% to 61% (p = 0.004); no significant dynamics were noted in the control group (p = 0.48). The presence of T2D significantly increases the risk of developing DD (p=0.04). The presence of T2D, increased fasting glucose levels, and an increased HOMA index were independent predictors of the development of DD. Impairment of LVEF was not observed in both groups. At the same time, the proportion of patients with reduced GLS (< -18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on T2D was demonstrated. The presence of obesity, an increase in the HOMA index and an increase in CRP levels are independent predictors of impaired GLS. Conclusions: T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up. Diastolic dysfunction is represented by delayed relaxation of the LV myocardium; with preserved LVEF, reduced 2D GLS identifies systolic dysfunction. The tight control of glycemia, lipidemia, blood pressure and body weight is associated with the absence of poor clinical outcomes.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Adeno-associated viruses (AAV) are widely used as viral vectors for gene delivery in mammalian cells. We focused on the efficacy of transduction of AAV 2/5, 2/6, 2/8 and 2/9 expressing GFP in 3T3-L1 murine preadipocyte cells by live imaging microscopy using IncuCyte S3 and flow cytom-etry. Three transduction modes were assessed: AAV transduction in 3T3-L1 preadipocyte cells with or without further differentiation into mature adipocyte-like cells and injection of AAVs in differ-entiated adipocyte-like cells. AAV2/6 demonstrated the highest transduction efficiency in 3T3-L1 preadipocytes, as it was 1.5–2-fold more effective than AAV2/5, and AAV2/8 in the range of viral concentrations from 2×104 to 1,6×105 VG/cell. AAV2/5 and AAV2/8 showed transduction effi-ciencies similar to each other. The expression of GFP under the CMV promoter remained stable for up to 20 days. The induction of 3T3-L1 differentiation in three days after AAV transduction did not alter the GFP expression level, and AAV2/6 showed the best transduction efficiency. AAV2/6 demonstrated the ability to transduce mature adipocytes. These results were confirmed by in vivo studies on C57BL6 mice AAV2/6 had the highest transducing activity on both inguinal and inter-scapular adipose tissue. Thus, AAV2/6 has demonstrated higher transduction efficacy compared to AAV2/5, AAV2/8 and AAV2/9 both in 3T3-L1 adipocytes and adipose tissue in vivo, which proves its usability along with AAV8 and AAV9 for gene delivery to adipocytes.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P&lt;0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P&lt;0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

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)

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

With an aging population, the prevalence of geriatric diseases is increasing, especially among older individuals who live alone. This study investigates the potential of using TV viewing patterns to detect these diseases by analyzing variables such as daily average viewing time, peak viewing hours, and channel-switching behaviors. Significant correlations between TV viewing patterns and early indicators of geriatric diseases (depression, activities of daily living (ADL) performance, and cognitive function) were found. The correlations between the Korean form of the Geriatric Depression Scale (KGDS) and daily average viewing time and excessive channel switching were 0.320 and 0.308, respectively. The Korean version of the Modified Barthel Index (KMBI) showed correlations of -0.313 with daily average viewing time and -0.352 with excessive channel switching. Participants were divided into groups based on scores, and significant differences in peak viewing hours were observed among the different groups. The Korean version of the Mini-Mental State Examination (MMSE-K) groups showed significant differences at 3, 4, and 5 PM. The KGDS and KMBI groups showed significant differences at 8 PM and midnight and 1 AM and 2 AM, respectively. These findings suggest that TV viewing patterns can serve as effective early diagnostic indicators for geriatric diseases.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

This study investigates job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesia and intensive care medicine in Germany, comparing them to their native German counterparts. Utilizing a cross-sectional survey design, the study collected data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the German version of the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Notably, migrant physicians reported higher difficulty and frustration in working with patients. Well-being ratings indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. The findings underscore the unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-D-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression.

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV recuperates cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague–Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to either WBV or control groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the control group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Abstract: Female pelvic floor dysfunction (FPFD) is a series of conditions caused by the displacement or dysfunction of the patient's pelvic organs due to defects, injuries, and deterioration of the pelvic floor supportive structures, with stress urinary incontinence and pelvic organ prolapse being the most common. The mechanism of pelvic floor dysfunction is complex and not yet fully understood, and is often related to one or more functional abnormalities of muscles, connective tissues, fascia, nerves and blood vessels. Specialized clinicians are often unable to cover the comprehensive medical professional information of various specialties such as gynecology and obstetrics, urology, anus and intestines, imaging, etc., and the systematic and comprehensive diagnosis and treatment of the disease will be limited. The application of artificial intelligence concepts in the medical field not only improves the diagnostic efficiency of physicians, but also provides reference and basis for the development of comprehensive treatment programs. This article follows and draws on the diagnosis and treatment process of pelvic floor dysfunction recommended in various guidelines, incorporates physical therapy techniques into the conventional non-surgical treatment of pelvic floor dysfunction, provides guidance for the diagnosis and treatment of pelvic floor dysfunction, and briefly introduces the clinical application and value of pelvic floor intelligent diagnosis and treatment in pelvic floor dysfunction.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

Abstract: Spinal disorders are some of the most prevalent health concerns, especially among stu-dents. Based on student demographics, this cross-sectional study evaluated the correlation be-tween functional tests (FT) and spinal range of motion (ROM). This study included 206 students from Vasile Alecsandri University of Bacău. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using Spearman correlation coefficient analysis. The results indicated a very strong re-lationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM of physical education department students compared to students from other de-partments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation be-tween FT and spinal ROM based on age (p > 0.05). The study results provide evidence of the pri-mary risk factors that predispose students to postural deviations. Practitioners and physiothera-pists can utilize these values as a reference for potential therapeutic interventions.

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

Consideration of the individual bone characteristics of the wrist plays a key role in well-functioning biomedical devices and successful surgical procedures. Although geometric differences and individual bone sizes have been analyzed in the literature, detailed morphologic descriptions and correlations covering the entire wrist reported in a clinical context are lacking. This study aimed to perform a comprehensive and automatic analysis of wrist morphology using the freely available “Open Source Carpal Database” (OSCD). We quantified the dimensions of each of the individual carpal bones and their combination. These dimensions were extracted in n=117 datasets of the wrist of the OSCD in anatomical directions and analyzed using descriptive statics and correlation analysis to investigate morphological characteristics under gender-specific aspects. We found that there exist statistical differences between genders, and we concluded that gender specificity is an important variable affecting the utilization of biomedical device designs and clinical treatment.

An understanding of the cultural conditions that determine the factors affecting nurses’ intention to leave is important for countries suffering from nurse shortage. Aim: to examine factors influencing intention to leave among female hospital nurses in a large Japanese sample, classified into four generations by age considering economic conditions. Methods: a cross-sectional survey with convenience sampling was conducted. Anonymous self-administered questionnaires were distributed to all nurses in 30 hospitals. To assess intention to leave, basic attributes, life conditions, work characteristics, and factors of psychosocial work environment were addressed. After classifying data into four generations based on age cohorts, we conducted multivariate logistic regression analysis using the completed data (N = 5,074, mean age = 36.24). Results: regardless of generational characteristics influenced by economic conditions, effort and monetary reward were generation-common factors. Over-commitment, social support, and the presence of a role model were generation-common factors in three generations. While having children increased intention to leave in the generation born 1965–1979, having family members in need of caregiving other than children decreased the risk in the generation born in the 1980s. Conclusion: generational countermeasures considering factors of psychosocial work environment and life conditions are needed to avert female nurse turnover.

There is a recent growth and development with regard to the female athlete. This trend has been reflected in a greater concern for aspects such as nutrition, body composition and the health of female athletes, given the repercussion of these factors on their sporting performance. The aim was to carry out an anthropometric and nutritional assessment of elite Spanish female football athletes based on different biochemical parameters. Ethical consent was obtained from a total of 21 players from a Spanish elite women's football team(20-33years). Anthropometric analysis was carried out using the International Society for the Advancement of Kineanthropometry(ISAK). Clinical analyses were performed by the club's medical staff at the beginning of the season through serum and fasting urine samples taken by the players. The athletes presented fat% of 19.1(SD±2.89). 100% of the players had Mg values within the reference values. Values below reference values were observed for Hb (85.7%), vit.D (33.3%), ferritin (23.8%), serum iron (28.6%), transferrin (4.8%) and TSI (42.9%); and above for CK (42.9%), basal cortisol (38.1%), testosterone (19%) and creatinine, total cholesterol, iron, transferrin, TSI and serotonin (4.8%). Differences in Mg levels were only observed between playing positions (p&lt;0.05). There were associations between age and vit.D levels (r=0.607), and weight with vit.D levels (-0.464) and blood cholesterol (-0.487) among others. Given the nutritional knowledge of Spanish elite female football players, as well as the prevalence of deficiencies in iron metabolism parameters and vit.D levels in athletes, the need to implement a correct nutritional assessment and education in this type of athletes is highlighted

Work disparities experienced by nurses in long-term care (LTC) can impact the retention, well-being, and health of this workforce. Despite the significant impact disparities experienced by nurses have on the workforce and LTC sector, a review of the available literature on work disparities has not been conducted on work disparities experienced by nurses in LTC. Consequently, this scoping review aimed to explore the nature and extent of research on meso-level work disparities experienced by nurses in LTC and how such disparities are linked with nurse health and well-being. Five databases were searched: MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO host). Of the 5,652 articles retrieved, 16 studies published between 1997 and 2024 met the inclusion criteria. The average number of work disparities within each study was 3.06 (minimum = 1, maximum = 6, SD = 1.62). Types of work disparities across the 16 studies were work opportunities (n = 19), work treatment (n = 18), job security (n = 8), and work compensation (n = 8). Only four articles investigated the association of a work disparity with a variable of health and well-being. Future research on how macro-level disparities intersect with meso-level work disparities may inform a contextual understanding of how disparities transpire in the work of nurses in LTC. Studies are required to address the gaps in knowledge regarding how work disparities negatively influence the health of nurses to inform better retention, well-being, and health of nurses in LTC.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Introduction: During the COVID-19 pandemic, many countries implemented restrictions, social distancing measures, and lockdowns to limit the spread of the disease. The lockdowns have affected children’s screen time (ST), pain, and physical activity (PA) levels. The present study aimed to explore the relationships between several personal factors during the COVID-19 pandemic. Methods: The caregivers of 329 children (median age=8 years) filled out an online self-reported survey about the children’s PA, ST, and pain before, during, and after the COVID-19 curfew. Spearman’s rank correlation coefficient was used to explore the associations between these variables. Results: After the curfew, pain that existed before the pandemic had a weak negative relationship with PA intensity (-0.11, p=0.04) and a weak positive relationship with ST (r=+0.12, p=0.04). There was a strong positive relationship between ST in all time periods (p&gt;0.01). PA and ST had a weak negative relationship (p&gt;0.05) during the curfew and after the curfew but not before the COVID-19 pandemic. Age had a weak positive correlation with ST in all time periods (p&gt;0.01). In addition, ST was affected by the curfew. Conclusion: The study findings indicated that young children had longer ST during the curfew and after the curfew compared with before the curfew. Increasing PA could lessen children’s ST, which could, in turn, increase the probability that their general pain would decrease.

Background: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Objectives: To investigate the efficacy of manual therapy (MT) program combined with Capacitive and Resistive Electric Transfer (TECAR) therapy in individuals with CNSLBP. Method: Sixty adults with CNSLBP were randomly equally divided into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet and the third group (Control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 hours with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), Pressure Pain Threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both in the second week as well as in the one-month follow-up (p < .001). Between-groups differences were also noticed between the two intervention groups in the second week (p < .05). Differences in the RMDQ score in the second week and on the one-month follow-up were detected between the intervention groups and the control group (p < .001), while differences between the two intervention groups were only detected in the one-month follow-up (p < .001). Regarding the PPT values, differences were found mainly between the MT + TECAR and the control group and between the MT + TECAR and the MT group (p < .05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant in the one-month follow-up (p < .05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region in both time points compared to the control group without, however, statistically significant differences between them (p> .05). Conclusion: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.

Spectral photon counting cone-beam CT imaging is challenged by individual pixel response behaviour, which leads to noisy projection images and subsequent image artefacts like rings. Existing methods to correct for this either use calibration measurements, like signal-to-thickness calibration (STC), or perform post-processing ring artefact correction of sinogram data or scan reconstructions, without taking the pixel response explicitly into account. Here we present a novel post-processing method (DAC-shifting), which explicitly measures the current pixel response using flat field images, and subsequently corrects the projection data. The DAC-shifting method was evaluated with a repeat series of spectral photon counting imaging (Medipix3) of a phantom with different density inserts, and in iodine K-edge imaging. The method was also compared against PMMA based STC. The DAC-shifting method was shown to be effective in correcting individual pixel response, and was robust against detector instability. On the contrary, STC correction showed varying results, which was almost as good as DAC-shifting when data was acquired just after STC calibration, but worse with larger time differences. In K-edge imaging, DAC-shifting provides a sharper attenuation peak, and more uniform CT values, which is expected to benefit iodine concentration quantification.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Selective mutism (SM) is an “Anxiety Disorder” characterized by a child’s “persistent inability” to communicate verbally in some (or all) contexts of social life that is associated with other cognitive-affective disorders. Cognitive-behavioural assessment and psychological intervention may be complex to be performed due to both the difficulty to administered standardized neuropsychological batteries (e.g., language-mediated tests) and the difficulty to involve family and teachers in the intervention program, respectively. Here, a single-case study is described in which a female Filipina child with SM underwent a comprehensive neuropsychological assessment and multimodal therapeutical intervention between the ages of 7 to 11 years. More specifically, the psychological intervention included cognitive-behavioral psychotherapy to both improve social-cognitive skills and learning abilities and to reduce anxiety, and speech therapy. Moreover, the parents and teachers were actively involved in the therapeutic process and they were also administered a psycho-education program. After this specific treatment, at the age of 11 years the girl began to verbalize in both therapy and school contexts, although she still was used to adopt non-verbal strategies. A parallel and gradual improvement in communicative-linguistic skills and school learning was also observed. In conclusion, the present report highlights the importance to apply an "integrated and multimodal intervention" to treat SM in children that includes also psycho-education intervention for both parents and teachers.

Background: Ovarian, cervical, and endometrial cancers stand as fatal health killers for women's mental and physical health, especially affecting female reproductive systems. Exploiting weakly supervised learning and explainable AI techniques are crucial for fast, accurate, and robust automatic marker detection, efficient prevention, and primary treatment of gynecological tumors. Methods: With respect to the PRIMSA methodology, weakly supervised learning schemes and deep learning-based schemes are investigated in the cross-subject fields of clinical diagnostic imaging and explainable AI technology. Related methods, opening research problems, and challenging subjects are explored in the screening and treatment of gynecological tumors and performing cancer image diagnosis in the latest study. Results: Keynote approaches combining ultrasound medicine, explainable AI, and clinical imaging technology are summarized. In combination with learning-based methods with medical imaging, prospective insights are put forward for refreshed concepts on treatments in the area of gynecological oncology, with a feasible range of applications for their corresponding AI techniques. Conclusions: Explainable AI and deep learning-based approaches are capable of performing accurate classification between benign and malignant tumors, yielding a pathway to care for women's health, improving the survival rate of patients, pacing with disease prediction, and matching the strategic goal of "Healthy China 2030".

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

Art therapy fosters emotional healing and growth. This process can offer healthcare professionals (HCPs) novel insights into patients’ medication experiences. We developed a Metaverse Art Gal-lery of Image Chronicles (MAGIC), which depicted patients’ medication experiences symbolically as hero-villain portrayals. This gallery aimed to enhance healthcare students’ learning through re-latable insights into patients’ medication therapies. A character sheet was used to craft patients’ personifications of their medication experiences. ChatGPT, NightCafe, Canva, HeyGen and Cam-tasia were used to generate hero-villain portraits based on the character traits and mounted in MAGIC, which consisted of three virtual realms, each with a unique theme. Alpha-testing among sixteen Generation Z healthcare learners indicated that the content in MAGIC enabled them to understand the concepts of medication adherence (93.7%), art therapy (87.5%) and how patients related to their medications (81.3%). Perceived playfulness (rs=0.925, p

Gene therapy is a medical approach capable of correcting genetic and epigenetic alterations in pathological conditions, including cancer. Different strategies have been pursued for cancer gene therapy, aiming to restore the function of tumor suppressor genes or inhibit oncogenes. These comprise the use of CRISPR/Cas9 gene editing technology and therapeutic oligonucleotides, such as microRNAs, anti-microRNAs, small interfering RNAs, DNAzymes, and epigenetic modifiers. However, despite great potential, their broad clinical use is hindered due to the lack of safe and efficient systems for targeted delivery to cancer cells. To this purpose, aptamers could represent an ideal tool. They are short single-stranded oligonucleotides that bind receptors selectively present or overexpressed on cancer cell membranes, often undergoing cell-specific internalization. Thanks to this last feature, numerous internalizing aptamers have been investigated as targeting moiety to deliver therapeutic oligonucleotides, viral vectors, and nanoparticle-based systems in preclinical studies. Here, we summarize the state-of-the-art of aptamer applications in cancer gene therapy, providing key examples and discussing their advantages, limitations, and clinical perspectives.

Isokinetic testing of the knee joint is the “gold standard” in strength assessment in sport especially in soccer, where it is part of pre-season screening to establish norms in case of injuries. There are many devices on the market that make it difficult to use of normative data. Isokinetics literature in females’ soccer players is scarce in comparison to males. Furthermore, evaluation protocols strongly differ from each other, using different ranges of speeds, movement patterns and output data. Thus, it is difficult for the researcher and the clinician to choose a correct protocol for isokinetic evaluation in female soccer players. The indexes of isokinetic performance that are widely accepted are the hamstring/quadriceps (H/Q) ratio and dominant/non-dominant (D/ND) ratio as reference. In this review are highlighted some common features of isokinetic testing in female soccer players of different levels of qualification. From this study, it emerges that, for a reliable test, 3 reps at the speed of 60°/sec in knee flexion/extension is preferable due to the high reliability and that an optimal H/Q ratio in healthy female soccer players of different level of qualification and age is 50%, while the interlimb differences (D/ND) should be below 10%.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

Background/Objectives: interpretation of evidence on de-escalation of triple therapy with with-drawal of inhaled corticosteroids (ICS) to dual bronchodilator therapy with a long-acting musca-rinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstruc-tive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discon-tinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: we searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov and CENTRAL for RCTs and observational studies from inception to March 22, 2024, investigating the effect of triple therapy de-escalation with withdrawal of ICS to dual therapy on the risk of COPD exacerbation, pneumonia and lung function. This study was registered with PROSPERO, CRD42024527942. Results: 3335 studies were screened; three RCTs and three real-world non-interventional studies were ultimately identified as eligible. Analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80 to 1.15; I²=77%) for ICS withdrawal compared with triple therapy continuation. Analysis according eosinophil levels showed that COPD subjects with ≥300 eosino-phils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated from ICS/LABA/LAMA to LABA/LAMA (pooled HR: 1.35, 95% CI 1.00-1.82; I2: 56%). The ICS withdrawal in favour of LABA/LAMA did not significantly affect the risk of mortality and pneumonia. Conclusions: the main findings of this meta-analysis are consistent with current recommendations and suggest that the use of eosinophil counts may be of help in guiding maintenance therapy. However, methodological heterogeneity between the included studies is evident.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Transcatheter Aortic Valve Implantation (TAVI) now represents the mainstay in the treatment of severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as a cornerstone. Leveraging data from multiple randomized controlled trials, current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without, or with atrial fibrillation respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual-patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Increased norepinephrine (NE) release from the sympathetic nerves during pregnancy in women or animal models, as occurs during stress, modifies the fetal environment and increases flow of NE to the fetus, programing the progeny and affecting its cardiovascular and metabolic function in adulthood. In the present work, gestating rats were exposed to stress during gestation and the female progeny was analyzed for heart and metabolic function. Pregnant Sprague–Dawley rats were exposed to cold stress (4 °C/3 h/day); rats’ female progeny were euthanized at 4, 20 and 60 days old and their hearts evaluated to determine the β-adrenergic receptor (βAR) mRNA, abundance and affinity to agonists and NE concentration. The in vivo response to glucose overload and the arterial pressure response to isoproterenol (ISO, 125 µg/kg weight/day/10 days) were monitored. Results: At 20 and 60 days old, stressed female progeny presented an increase in ventricular weight and no changes in the cardiac NE as compared with their age-matched controls. The β1AR mRNA in control rats decreased between 4 and 20 days of age, but stressed rats maintained 50% higher levels of mRNA as compared with their age-matched controls. This difference was also found in the protein abundance of β1AR. No differences were found at 60 days old. The β2AR mRNA levels were higher than in controls at both 4 and 20 days old, but not expressed in the amount of protein. An increase in the ratio of β1/β2 receptors was found at 20 days old but not at 60 days old. The displacement of 3H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist) showed decreased affinity (at 60 days old) but no changes in the βAR number. In vivo exposure to ISO induced a β-adrenergic overload and provoked death in 40% of stressed females by day 3 of ISO treatment. Regarding metabolic function, we found that stressed rats presented insulin resistance when adults. These data suggest permanent changes to the heart’s adrenergic response and metabolic function after rat progeny were stressed in the uterus.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

The importance of Muscovy ducks in industrial poultry production is growing; however, little is known about the physiology of their reproductive cycles. This study investigated the influence of male biostimulation on female ducks before the commencement of the laying phase. A total of 15 female Muscovites were kept in contact with a male duck until the point of laying, while 15 other females were kept without any contact with a male conspecific. Before reaching egg-laying maturity, the cloacae of 29 adult ducks were subjected to daily clinical assessments. The evaluations yielded four unique categories of outcomes, determined by assessing factors such as the degree of redness and protrusion of the mucous membrane, moisture level, and swelling of the cloacal sphincter muscle. In terms of biostimulation, the findings demonstrated that, on average, ducks in contact with males laid the first egg 16 days earlier than isolated ducks. Furthermore, there was no significant difference observed in the mean initial egg weight between both groups (p = 0.841). The changes in the cloacal morphology indicated significant morphological changes 25–26 days before laying. Efforts to improve Muscovy production and develop biotechnological techniques to modify the reproductive cycle will benefit from these advancements.

This case report examines the impact of a novel Combined Neuromuscular Electrical Stimulation (Comb-NMES) regimen on muscle glucose signaling, fiber type distribution, and metabolic function in a patient with acute spinal cord injury (SCI) and lower motor neuron lesions (LMNLs). A 32-year-old male with complete T9 SCI underwent a ten-session Comb-NMES intervention targeting the quadriceps. Muscle biopsies and blood samples were analyzed pre- and post-intervention to evaluate changes in muscle fiber types, key metabolic proteins, fasting insulin, glucose, and lipid profiles. The intervention led to a 74.7%, and 28.2% reduction in fasting insulin and glucose, respectively. Muscle analysis showed significant increases in CaMK II, Hexokinase II, and IRS-1, indicating improved glucose metabolism. Comb-NMES training markedly improved metabolic control and muscle glucose metabolism in a patient with acute SCI and LMNLs. Enhanced insulin sensitivity and glucose utilization were evidenced by upregulated metabolic proteins which suggests Comb-NMES is a promising intervention for improving muscle and metabolic health in SCI patients with LMNLs. Further studies are needed to confirm these benefits and explore long-term effects.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGen database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined by Mendelian randomization. 253 genes that exerted trans-regulatory impacts on 1,439 genes were identified. Majority of the identified gene-pairs aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. Genes with higher gene expression heritabilities displayed broader regulatory impact in the network. The network displayed the scale-free topology, this provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and higher expression of HHEX is associated with lower triglycerides and risk of type 2 diabetes. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The identified network displayed scale-free topology indicating the hub genes of a tissue-specific network could be targeted to prevent disease outcomes.

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.

Abstract: Background: We previously found that forest bathing significantly reduced the scores for negative emotions and in-creased the score for vigor in the profile of mood states (POMS) test in both males and females and increased the sero-tonin level in males, indicating the potential for beneficial effect on depressive status. In the present study, we investi-gated the effects of forest bathing on the levels of serotonin, oxytocin and insulin-like growth factor I (IGF-1) in blood, Self-Rating Depression Scale (SDS) scores, POMS, subjective fatigue symptoms and subjective sleep quality in female subjects with depression/depressive tendencies. Methods: Thirty-one female subjects aged 40.1±2.4 years with depression/depressive tendencies were recruited after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin in Nagano Prefecture, and to a city area of Nagano Prefecture as a control in June 2023. On both trips, they walked 2.2-2.5 km for two hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin, oxytocin, IGF-1 and lactic acid in blood were measured. The SDS scores, POMS test, and questionnaires for subjective fatigue symptoms and subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Nippon Medical School Central Ethics Committee approved this study. Results: Forest bathing significantly decreased SDS scores and the effect lasted for one week after forest bathing. Forest bath-ing also significantly increased the level of serotonin in serum in subjects who were not taking antidepressants, significantly increased the levels of oxytocin and IGF-1 in blood, significantly increased the scores for vigor-activity and friendliness and de-creased the scores for anger-hostility, confusion-bewilderment, fatigue-inertia, tension-anxiety, depression-dejection and total mood disturbance compared with city walking (all p

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

The main purpose of the study was to study the effects of a specific rowing ergometer training program on the athletic performance of young adolescents (n=56; 11.73 ± 1.4 years old) com-pared to a workout based on general strength training. Eight-week training program was im-plemented, with four sessions per week and two-hours per session. Sample was divided in two groups: a control group (CG) that performed circuit training with exercises aimed at building general strength and an experimental group (EG) who focused on specifically training on a rowing ergometer (rowing machine). The data obtained in a rowing meter test over the compe-tition distance were analyzed to obtain the average power attained (W) at the beginning of the training, at the middle (4 weeks), at the end of the training (8 weeks) and one year after the ex-perimentation. The results show that, although both forms of training improve the average W obtained in both categories, the EG subjects (+29.94W) obtained better averages in all phases of the study compared to the CG (+5.88W). Furthermore, this increase was greater in male rowers (+ 34.06W) than in female rowers (+24.54W). These results reveal that a specific rower rowing ergometer training program has a significant effect than a general strength program and these effects can even be observed a year after the intervention.

Background: Accurate prediction of patients’ response to therapy is clinically indispensable, howbeit challenging. With increased understanding of the human genome and malignancies, there is the renaissance of in silico pharmacogenomics with renewed interest in drug response predictability based on gene-drug interaction. Objective: Evidence-based transcript-proteome profiling is essential for synthesizing clinically applicable algorithms for predicting response to anticancer therapy, including immune checkpoint blockade (ICBT); thus, saving physicians’ time, reducing polypharmacy, and curtailing unnecessary treatment expense. In this study, we tested and validated the hypothesis that a selected proteomic signature in ICBT-naïve patients is sufficient for the prediction of response to ICBT. Methods: Using a multimodal approach consisting of computational pharmacogenomics, transcript-proteome analytics, mathematical modeling, and machine learning systems; we delineated therapy-sensitivity and stratified patients into graduated response groups based on their proteomic profile. Protein expression levels in our cohort tissue specimens were evaluated based on T cell- and non-T cell- inflamed phenotypes by immunohistochemistry. Results: We established β-catenin, PDL1, CD3 and CD8 expression-based ICBT response model. Statistical regression models validated the predictive association between our predefined algorithms and therapeutic outcome. Interestingly, our 4-gene prediction classifier was constitutively independent of tumor tissue origin, correctly stratified patients into high-, low-, and non- responders pre-treatment, with high prediction accuracy, and exhibited good association with patients’ performance status and prognosis (p < 0.01). Conclusion: Our findings demonstrate the possibility of accurate proteomics based ICBT response prediction and provide a putative basis for drug response prediction based on selective proteome profile in untreated cancer patients.

Neurotensin (NT) is a peptide involved in digestion, neuromodulation, and cancer progression. NT and its receptors (NTR1 and SORT1 mainly) have been widely studied in oncology. Data show NT expression is under the control of sex steroid hormones, in particular estradiol. We focused on its involvement in three main female hormone-sensitive cancers: breast, ovarian, and endometrial cancer in a narrative review. NT, NTR1 and SORT1 are mostly expressed in these three cancers and their involvement in oncologic processes such as proliferation and invasion seems to match, as does their impact on prognosis for most. The development of NT receptor-targeted therapies, including theranostics and radioligand treatments, presents a promising avenue for personalized cancer treatment.

Eating disorders (EDs) refer to a group of diseases characterized by a strong tendency toward chronicity, often involving distortions in body image distortion and other related symptoms The prevalence of EDs has increased in recent years, specifically in athletic populations. Therefore, the purpose of this study was to analyse risky eating attitudes in a sample of 1102 subjects from Se-ville (Spain): 142 women and 960 men aged between 15-25 years old. An online survey, designed using Google Forms, consisted of three questionnaires (EAT-26, SCOFF, and BITE), were com-pleted individually and anonymously. With regards to the cut-off points, the percentage of posi-tive cases with significant scores was 11.43% for EAT-26, 31.22% for SCOFF and 4.36% for BITE. The study found that the probability of testing positive for EDs is significantly higher in women than in men (p < 0.001). Specifically, the risk attitude for EDs in female athletes measured by the EAT-26 test is three times higher than in male athletes, while the risk attitude measured by the SCOFF test is twice as high in females. Risk attitude for EDs in athletes measured by the BITE test is 8 times higher in females than in males. This study’s findings confirm several important as-sumptions made at the outset of the research. There is indeed a higher risk of EDs in athlete populations. Moreover, all three tests therefore show a higher frequency of possible events of EDs in women, with very similar percentages of difference between sexes. The tests also confirm the role played by the coaches in the prevention of EDs in sports and their capacity to reduce ab-normal food-related behaviours. Thus, the future inclusion of these tests in the screening of athletes is highly recommended.

Despite saltmarshes being considered as nature-based solutions (NbS) towards climate change mitigation, India’s saltmarsh ecosystems are least studied. This study quantifies the seasonal variation in carbon stocks mono-specific saltmarsh species (Porteresia coarctata) and its potential to play an important role in India’s climate change mitigation plans. Seasonal (pre-and post-monsoon) sampling of P. coarctata surface water, biomass and 30 cm sediment core was collected across four locations on the east coast of India to quantify sediment dry bulk density (DBD), organic matter (OM%), organic carbon (Corg%), Corg stocks of sediment and biomass, total carbon (C%) and nitrogen (N%) and stable isotopes of δ13C and δ15N. In general, the sediment DBD, OM and Corg of P. coarctata meadows was higher in post-monsoon and was influenced by salinity and pH changes. Isotope (δ¹³C) modelling of various sediment C sources suggested, particulate organic matter (POM) contribution was highest (0.04-0.79%) followed by P. coarctata (0.01–052%) and other macrophytes across our study locations. The seasonal variation of δ¹³C showed increased contribution of marine derived particulate and dissolved organic matter into P. coarctata meadows in post-monsoon season. Heavier δ¹⁵N values were observed in post-monsoon season suggesting anthropogenic input, that was utilized by P. coarctata to increase its above and below-ground biomass and shoot density. The combined ecosystem (30 cm sediment + biomass) Corg stocks of P. coarctata was 1.7-fold higher in post-monsoon (4021.20± 917 Mg C) compared to pre-monsoon (2297.36 ±647 Mg C) season among the four locations with a sediment Corg contribution >70%. Based on the International Panel for Climate Change Tier II assessment the P. coarctata meadows (443 ha) can help in avoiding the pre and post-monsoon emissions of 8431.34 and 14757.84 Mg CO₂ respectively. The combined price of the total CO₂ equivalent stored in P. coarctata meadows in pre- and post-monsoon is US$ 14.50 and US$ 25.38 million respectively. Further studies quantifying the NbS potential of P. coarctata mono-specific and mixed meadows of India’s coast is needed along with integration of saltmarsh ecosystems into India’s National Action Plan on Climate Change.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms pathway in estrogen-deficient diabetic female mice, cell lines, and patients with T2D in female. Initially, female mice fed a HFHSD exhibited delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment of miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protect against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

Objectives: Stress urinary incontinence (SUI) negatively affects the quality of life and sexual function in women. This study aimed to evaluate the efficacy of radiofrequency (RF) therapy in reducing SUI symptoms and its impact on sexual function. Methods: Thirty-four women with SUI were enrolled and underwent a single RF treatment session using the Viveve® System (Viveve Medical Inc., USA) with parameters of 90 J/cm² and 220 pulses per hour. Assessments at baseline and 6 months post-treatment included perineal ultrasound and personal interviews to evaluate lower urinary tract symptoms and sexual function. Urodynamic studies, voiding diaries, and questionnaires such as the Female Sexual Function Index (FSFI), Overactive Bladder Symp-tom Score (OABSS), Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Question-naire-7 (IIQ-7), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) measured outcomes. Results: RF therapy significantly improved sexual function, with higher FSFI scores in all domains except pain at 6 months. SUI symptoms were significantly re-duced, as indicated by improved scores on OABSS, UDI-6, IIQ-7, and ICIQ-SF, alongside better voiding diary results. Anatomical changes included reduced bladder neck mobility, decreased vaginal width, and a reduced rotation angle of the proximal urethra. Conclusions: RF therapy is effective and safe for treating mild to moderate SUI and enhances sexual function, potentially due to changes in vaginal topography. These results suggest RF therapy as a viable non-surgical op-tion for managing SUI and improving sexual health.

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

The global increase in population has placed significant pressure on food security, leading to the emergence of aquaculture as a vital source of aquatic foods. However, rising costs and the limited availability of fishmeal in aquafeeds have spurred the search for alternative protein sources. While plant-based ingredients have been integrated into commercial aquafeeds, they come with challenges, including low protein content, palatability issues, and the presence of antinutritional factors. In this context, fish silage, derived from fish waste and discarded fish, stands out as a promising alternative technology due to its cost-effectiveness and sustainability attributes. The production of fish silage involves the addition of organic/inorganic acids or lactic acid bacteria to homogenized fish waste. This process yields a valuable mixture rich in peptides, free amino acids, and partially hydrolyzed proteins, offering significant nutritional benefits for animal diets. Beyond its nutritional advantages, fish silage contributes to environmental sustainability by reducing the impact of waste disposal and enhancing the value of fish waste. The objective of this review is to promote sustainable practices in the aquaculture industry in response to the increasing demand for high-quality feed nutrients. To achieve this, it includes an analysis of research results related to silage technology, an appraisal of the advantages and disadvantages of using fish silage as a feed additive, and a focus on emerging trends in this field.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is believed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. After reviewing the available data on epidemiology and evolution of respiratory viruses, this study examines the effect of varying vaccination rates across different age groups during the 2019/2020 influenza season in Saudi Arabia. Utilizing an age-structured SEIR (Susceptible–Exposed–Infectious–Recovered) model, it develops customized vaccination policies by considering age-specific incidence rates. This pioneering research segments the population into five age groups—infants and school-aged children, junior and older youth, young adults and adults, middle-aged, and seniors—across five regional areas in Saudi Arabis: Eastern, Central, Northern, Western, and Southern. A contact matrix, compiled from multiple sources, is used to delineate the dynamics of influenza transmission. The study undertakes a thorough comparison of three distinct vaccination scenarios: no vaccination, national vaccination, and optimized vaccine allocation policy, under various potential pandemic situations. It examines their impact on vaccination campaigns in terms of the total number of infections, mortality, and morbidity rates. The results emphasize the crucial impact of population demographics on disease transmission and vaccine distribution. According to the findings, the optimized vaccination scenario proved to be the most effective strategy in all scenarios.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between response to the anti-PD-1 therapy and the baseline gut microbiome in the Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy and 10 healthy subjects were recruited. Response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis, and metataxonomics of the microbiota. The Bacteroidota to Firmicutes ratio was higher, and the richness was decreased in the responders. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas non-responder gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis, and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption, but also gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota alongside diet were found associated with response to the therapy in the Polish population of melanoma patients.

In 2018, Iran witnessed approximately 21,000 fatalities resulting from road accidents, ranking it as the fifth leading cause of death across all age groups. These incidents carry substantial economic and social burden for the nation, claiming more than 5% of its GDP. Human behavior emerges as a significant contributing factor to high-risk driving offenses. It has been proposed that by influencing general deterrence, a rigorous defense can be established against such violations. Various theories posit that by reinforcing or diminishing influential factors, general deterrence perception can be molded, presenting a potential avenue for an effective deterrent against traffic infractions. This study examines deterrence perceptions prevailing among the public in Iran regarding the enforcement of traffic laws. Employing Structural Equation Modeling (SEM), we delve into the intricate relationships between variables, allowing for a comprehensive exploration of the factors influencing general deterrence. The study draws on the data derived from a survey comprising 548 questionnaires for modeling purposes. An innovative concept, private sector enforcement, is introduced and incorporated into the questioning and modeling process. The findings reveal that socioeconomic status (p-value&lt;0.01), police enforcement (p-value&lt;0.05), private sector enforcement (p-value&lt;0.05), specific deterrence (p-value&lt;0.01), and the use of technology (p-value&lt;0.01) have direct and indirect impacts on the general deterrence perception of drivers.

Objective: To investigate whether the relationships between acute care occupational therapy (OT) and physical therapy (PT) utilization and community discharge are moderated by functional or physical performance at discharge among individuals hospitalized with traumatic brain injury (TBI). Setting: 14 acute care hospitals in the state of Colorado. Participants: We studied 5,599 adults hospitalized with TBI between June 2018 and April 2021. Design: In a secondary analysis of de-identified electronic health record (EHR) data, multivariable moderation logistic regression models were performed to calculate odds ratios (ORs) for the likelihood of community discharge among patients who utilized OT/PT services. Main Measures: Functional (activities of daily living [ADL]) and physical (mobility) performance at discharge, OT and PT utilization, and community discharge status. Results: Overall, 67% of patients discharged to the community. The mean age of the sample was 55 years (SD = 20 years). Most participants were male (64%) and non-Hispanic white (72%). Mean hospital length of stay was 6 days (SD = 6 days). Both OT and PT utilization (OT: OR= 1.21, 95% CI [1.11, 1.33]; PT: OR= 1.22, 95% CI [1.14, 1.30]) and discharge ADL and mobility scores (ADL: OR= 1.34, 95% CI [1.30, 1.39]; mobility: OR= 1.38, 95% CI [1.33, 1.42]) were significantly and positively associated with community discharge. The OT and PT utilization-by-discharge ADL and mobility interaction terms yielded slightly negative, but statistically significant moderation effects in both models (ORs= 0.99, 95% CIs [0.98, 1.00]); indicating the magnitude of the OT and PT utilization effect diminished as ADL and mobility scores increased. Several sociodemographic characteristics and clinical factors were also independently associated with community discharge in both models (p-values

Athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer spectrum to avoid overtraining and optimize the effects of training.

Primary urethral malignancies are rare in clinical practice and elderly female are prone to suffer. The cause of PUC is unknown and may be related to long-term chronic inflammation, infection, sexual intercourse, pregnancy and irritation of the urethra. Incipient symptom of PUC is not distinctness and can easily lead to misdiagnosis. The final diagnosis relied on transvaginal ultrasound-guided mass biopsy and urethral biopsy. Early tumor treatment is mainly based on surgical resection. For advanced tumors, it is recommended to adopt a comprehensive treatment plan combining surgery, radiotherapy and chemotherapy We report this case with the aim of bringing attention to that primary urethral cancer progresses rapidly and has a poor prognosis, it is urged to call for a need of diagnostic and treatment specification.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

This study re-introduces a protein-free rapid test method for nucleic acids on paper based lateral flow assays utilizing special multichannel nitrocellulose membranes and DNA-Gold conjugates, achieving significantly enhanced sensitivity, easier protocols, reduced time of detection, reduced costs of pro-duction and advanced multiplexing possibilities. It is shown for the first time a protein-free nucleic acid based lateral flow assay (NALFA) with a limit of detection of 1 pmol of DNA. The total production duration of such an assay was successfully reduced from the currently known several days to just a few hours. The simplification and acceleration of the protocol make the method more accessible and practical for various applications. The developed method supports multiplexing, enabling the sim-ultaneous detection of up to six DNA targets. This multiplexing capability is a significant improve-ment over traditional line tests and offers more comprehensive diagnostic potential in a single assay. The approach significantly reduces the run time compared to traditional line tests, which enhances the efficiency of diagnostic procedures. The protein-free aspect of this assay minimizes the prevalent complications of cross-reactivity in immunoassays especially in cases of multiplexing. It is also demonstrated that the NALFA developed in this study is amplification-free and hence does not rely on specialized technicians, nor does it involve labour-intensive steps like DNA extraction and PCR processes. Overall, this study presents a robust, efficient, and highly sensitive platform for DNA or RNA detection, addressing several limitations of current methods documented in the literature. The advancements in sensitivity, cost reduction, production time, and multiplexing capabilities mark a substantial improvement, holding great potential for various applications in diagnostics, forensics, and molecular biology.

Background/Objectives: This study looks at how a kinematic chain exercise regimen that targets the lower, core, and upper body affects university shot put participants' shoulder muscle strength and throwing efficiency. This study fills an apparent research void on shot put training approaches by presenting a comprehensive kinematic chain workout program. It was anticipated that this method would improve performance the most, considering the complex biomechanical require-ments of the sport. Methodology: Athletes, seventy in age (19.87 ± 1.31 years), were assigned into two groups at random: experimental (n = 35) and control (n = 35). While the control group carried on with their usual training, the experimental group participated in an 8-week kinematic chain training program, pre- and post-training evaluations were carried out to evaluate shot put throwing ability, shoulder muscle strength, and participant satisfaction with the exercise regimen. Results: demonstrated that, when compared to the control group, the athletes in the kinematic chain program had a significantly improved throwing distance (p = 0.01) and shoulder muscle strength (p = 0.01). Furthermore, there was a significant difference (p = 0.005) in the athletes' satisfaction levels with the workout program among those in the experimental group. This implies that a kinematic chain-focused strategy improves performance and emphasizes the significance this type of training is for shot put athlete performance. Conclusion: As an improvement forward in sports science, the study's finding promotes the inclusion of kinematic chain workouts in shot put training programs and calls for more research on kinematic chain-based approaches in a variety of sports.

CO2 emission activity of xylotrophic fungi response to an increase in temperature in the range of 10-30 °C on the example of pure dikaryotic cultures of Fomes fomentarius s. str., F. inzengae, Fomitopsis betulina, F. pinicola, Phellinus igniarius was analyzed. Emission activity was assessed by the difference in CO2 concentration in 0.5-liter exposure chambers with Petri dishes with mycelium growing on agar at the beginning of exposure and an hour later using a Gasmet DX-4030 FTIR spectrometer (Gasmet Technologies Oy, Finland), error measurements ±50 ppm. Specific (μg CO2/cm2/h) and total (μg CO2/h) emission activity and its relationship with temperature and size (area) of the mycelium were assessed. It has been shown that in the range of 10-30 °C, the specific and total CO2 emission activity of the mycelium is closely and positively related to temperature. Specific emission, which is an indicator of the respiratory activity of the mycelium, does not depend on its size; its only driver is temperature, the relationship with which is linear: an increase in temperature by 10 °C causes an increase in the specific emission activity of the mycelium by 1.7 times. The total CO2 emission activity, which is an indicator of the total amount of CO2 emitted, is directly proportional to the specific emission activity and the size of the mycelium. In the range of 10-30 °C, an increase in temperature causes an almost equal increase in both the specific emission activity of the mycelium (Q10 1.7) and its growth (Q10 1.5) and causes an exponential increase in the total emission of CO2. This must be taken into account when predicting CO2 emissions from woody debris under climate change, as it could potentially contribute to accelerating climate change.