Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus while less common, tetanus is a serious disease following contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is this disease primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, malignant edema can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causing sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

The stock beta coefficient literature extensively discusses the proper methods for the estimation of beta as well as its use in asset valuation. However, there are relatively few references with respect to the appropriate time horizon that investors should utilize when evaluating the risk-return relationship of a stock. We examine the appropriate time horizon for beta estimation differentiating our results by sector according to the Industry Classification Benchmark. We employ data from the NYSE and we estimate varying lengths of beta employing data from 30 to 250 trading days. The constructed beta series is then examined for the presence of breaks using the endogenous structural break literature. Results show evidence against the use of betas that employ more than 90 trading days of data provisional to the sector under study.

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

The study of precipitation amount at different time scales constitutes an important issue in climate research and risk assessment. When dealing with daily totals, a frequent but sometimes underestimated problem is at what time the observation day begins. The choice of different starting times may lead to incompatibility between stations and incorrect identification of extreme events. In this work, the problem of temporal misalignment between precipitation datasets characterized by different starting time of the observation day is analyzed. The most widely used adjustment methods (1day and uniform shift) and two methods based on reanalysis (NOAA and ERA5) are evaluated in terms of temporal alignment, precipitation statistics and percentile distributions. As test series, the precipitation amount collected from 9 a.m. local time (09 LT) on the previous day to 09 LT on the target day (9-9 datasets) of the Padua and nearby stations in the period 1993-2022 have been selected. Results show that the reanalysis-based methods, in particular ERA5, outperform the others in temporal alignment, regardless the station. But, for the periods in which reanalysis data are not available, “1day” method, which shifts the daily amount back one calendar day, and “unif” method, which distributes uniformly the daily total from a 2-day moving window surrounding the target date, can be considered valid alternatives. On the other side, concerning the precipitation statistics, the reanalysis-based methods are not the best option, as they increase the precipitation frequency and reduce the mean value over wet days, NOAA much more than ERA5. Nevertheless, the uniform method provides a larger deviation from the original daily series. The use of the series of a station nearby the target one, which is mandatory in case of missing data, gives similar or better results than applying any adjustment method to the 9-9 series. General conclusions can hardly be drawn as they depend on the method and station. For the Padua dataset, the analysis was repeated at monthly and seasonal resolution. In general, the adjustment series show the most relevant changes in the precipitation statistics in summer and less temporal alignment with the original series in summer and autumn, the two seasons mainly affected by heavy rains in Padua. Finally, the percentiles distribution, analyzed for all the methods and stations, indicates that any adjustment method underestimates the percentile values, except ERA5. Only Legnaro, the station most correlated with Padua, gives results like ERA5.

During public health events, Active Mobility (walking and cycling) plays an important role in securing residents' travel. To enhance the resilience of urban transportation, this article integrates the travel environment elements for walking and cycling and constructs a travel environment for Active Mobility evaluation index system. This article uses survey data from the main urban area of Harbin in the context of the COVID-19 pandemic in May 2022, and combines the Gradient Boosting Decision Tree (GBDT) and Impact-Asymmetry Analysis (IAA) methods to analyze the satisfaction of the travel environment for Active Mobility. It proposes strategies for optimizing the travel environment for Active Mobility, ensuring residents' travel during public health events, guiding them to adopt Active Mobility, and improving urban transportation resilience. This research shows that Active Mobility can enhance urban transportation resilience. In addition, there are differences in resident demand for walking and cycling environments in the travel environment for Active Mobility. Residents are more concerned about the comfort of the walking environment, while they prioritize the convenience of the cycling environment.

Degnala is one of the main mycotoxicoses that affects buffaloes, and the fungus Fusarium spp. is the main causative agent. This disease is strongly related to the supply of rice straw to buffaloes and is considered endemic to regions where this crop is cultivated. Cases of the disease are concentrated in the winter, when conditions favour fungal growth in inadequately stored rice straw. Degnala is characterized by necrosis and gangrene of the extremities, including the tail, lower limbs, ears, tongue, muzzle and teats. The pelvic limbs are more affected than the thoracic limbs. A tortuous appearance of the tail is very common, and cracks or corneal loss of the hooves may occur, with exposure of the blades and even the bones. There is no diagnostic method for identifying the disease in animals other than the clinical and epidemiological criteria associated with fungal culture of rice straw samples. There is no treatment that neutralizes the effects of the toxins, and the treatment currently used is a palliative and supportive method consisting of pentasulfate solution, anti-Degnala liquid, 2% nitroglycerin ointment and broad-spectrum antibiotics for secondary infections. In addition, the management of drying straw and proper storage are essential for controlling this disease.

Tellurium exhibits exceptional intrinsic electronic properties. However, investigations into the modulation of tellurium's electronic properties through physical modification are notably scarce. Here, we present a comprehensive study focused on the evolution of the electronic properties of tellurium crystal flakes under plasma irradiation treatment by employing conductive atomic force microscopy and Raman spectroscopy. The plasma-treated tellurium experienced a process of defect generation through lattice broken. Prior to the degradation of electronic transport performance due to plasma irradiation treatment, a remarkable observation emerged: in the low-energy region of hydrogen plasma-treated tellurium, a notable enhancement in conductivity was unexpectedly detected. The mechanism underlying this enhancement in electronic transport performance was thoroughly elucidated by comparing it with the electronic structure induced by argon plasma irradiation. This study not only fundamentally uncovers the effects of plasma irradiation on tellurium crystal flakes, but also unearths an unprecedented trend of enhanced electronic transport performance at low irradiation energies when utilizing hydrogen plasma. This abnormal trend bears significant implications for guiding the prospective application of tellurium-based 2D materials in the realm of electronic devices.

Adenomyosis, a benign gynecological condition characterized by the infiltration of endometrial tissue into the myometrium, poses significant challenges to women's reproductive health. Recently, the landscape of adenomyosis diagnosis transformed significantly, thanks to advancements in imaging technologies such as transvaginal ultrasound and magnetic resonance imaging. This lead to a noticeable shift in the demographic profile of patients diagnosed with adenomyosis, including younger women of reproductive age who frequently present with a diverse array of symptoms. Approximately 20% of women are affected by adenomyosis. Adenomyosis manifests with various subtypes, distinct epidemiological profiles, symptomatology, and treatment responses, necessitating tailored approaches for optimal management. Despite its clinical significance, adenomyosis remains understudied, resulting in a significant disparity in research and literature compared to other gynecological conditions. The severity of adenomyosis is compounded when coexisting with endometriosis, particularly deep infiltrating endometriosis (DIE), leading to exacerbated fertility issues and severe symptomatology. The wide range of symptoms, including adverse pregnancy outcomes such as pre-eclampsia, highlights its wider impact and emphasizes the need for increased awareness of the condition. Furthermore, Adenomyosis is frequently associated with treatment failure in endometriosis, contributing to dienogest resistance, elevated discontinuation rates, and persistent pain post endometriosis surgery. Additionally, the lack of specific treatments tailored to adenomyosis poses a considerable challenge in clinical management.

Candidiasis is a significant fungal infection caused by various species of the genus Candida, posing health challenges to a wide range of animals, including Choloepus species (two-toed sloths). This review article aims to provide a comprehensive understanding of candidiasis in Choloepus sp., highlighting the etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention strategies.The article begins by examining the causative agents, primarily focusing on Candida albicans, which is the most commonly implicated species in candidiasis. The epidemiological aspects are discussed, emphasizing the prevalence of candidiasis in wild and captive Choloepus populations and identifying predisposing factors such as immunosuppression, stress, poor nutrition, and environmental conditions. Pathogenesis is explored, detailing the mechanisms through which Candida species invade host tissues and evade immune responses. Clinical manifestations in Choloepus sp. are described, including oral thrush, cutaneous lesions, and gastrointestinal infections, and their impact on the health and behavior of affected individuals. Diagnostic methods, including culture techniques, histopathology, and molecular assays, are reviewed to highlight their roles in accurately identifying Candida infections. The article also covers treatment options, focusing on antifungal therapies and supportive care tailored to the unique physiology of Choloepus sp. Finally, prevention and management strategies are discussed, emphasizing the importance of maintaining optimal husbandry practices, regular health monitoring, and early intervention to reduce the incidence and impact of candidiasis in Choloepus populations. This review underscores the need for further research to enhance our understanding of candidiasis and improve health outcomes for these unique and vulnerable animals.

Background: Gender differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, gender-specific analysis remains underexplored. This retrospective study aimed to evaluate the gender-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods: Data were collected from 47 patients (31 women, 16 men), with age > 18 years, BMI ≥ 30 kg/m^2, absence of T2D, and with exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results: Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, % WL, WL >5% and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant gender differences were observed in glucose metabolism or renal function. Conclusion: This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

Electrochemical methods are used for the treatment of both municipal and industrial wastewater, either independently or in conjunction with biological methods. This conjunction is used for pretreatment or posttreatment of biologically treated wastewater. In our work, we focused on the combination of these processes, where pre-electrolysis was used to produce dissolved iron before the activation process. Electrolysis was also directly introduced into the activation using either iron or carbon electrodes. The surface of one iron electrode was 32.2 cm2, the applied voltage was 21 V, and the supplied current was 270 mA. The surface of one carbon electrode was 7.54 cm2, the supplied current was 82.5 mA, and the applied voltage was 21 V. From laboratory research on the treatment of synthetic municipal wastewater using a combination of electrolysis and activation processes, it resulted that the use of iron electrodes increased the efficiency of phosphorus removal compared to its precipitation with iron salts. The electrolysis had a positive effect on the sedimentation properties of sludge and the destruction of filamentous microorganisms. Electrolysis negatively affected the respiration rates of activated sludge and the efficiency of denitrification. However, it did not have a negative impact on the nitrification activity of the sludge.

The development of computational acoustics allows simulation of sound generation and propagation in complex environment. In particular, meshfree methods are widely used to solve acoustics problems through arbitrarily distributed field points and approximation smoothness flexibility. As a Lagrangian meshfree method, smoothed particle hydrodynamics (SPH) method reduce the difficulty in solving problems with deformable boundaries, complex topologies, or multiphase medium. The traditional SPH method has been applied in acoustic simulation. This study presents the corrective smoothed particle method (CSPM), which is a combination of SPH kernel estimate and Taylor series expansion. The CSPM is introduced as a Lagrangian approach to improve accuracy in solving acoustic wave equations in the time domain. Moreover, a boundary treatment technique based on the hybrid meshfree and finite difference time domain (FDTD) method is proposed to represent different acoustic boundaries with particles. To model sound propagation in pipes with different boundaries, soft, rigid, and absorbing boundary conditions are built with this technique. Numerical results show that the CSPM algorithm is consistent and demonstrates convergence with exact solutions. Main computational parameters are discussed, and different boundary conditions are validated to be effective for benchmark problems in computational acoustics.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 hour, patients took 50 mg lasmiditan within 2 hours of migraine onset. Patients recorded headache intensity and adverse events(AEs) caused by lasmiditan at 1, 2, and 4 hours after intake of additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 hour after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 hour after lasmiditan intake. Our study revealed the significant headache reliefs provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short term. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low to intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical assessments, PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: forty patients were initially included, with 15 lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible and effective in the index lesion treatment of low-intermediate risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Objective: This prospective study aimed to compare the efficacy of caudal block (CB) and inguinal block (IB) for providing additional analgesia during unilateral orchidopexy. Methods: Seventy-two boys aged <48 months, classified as ASA I/II, were assigned into CB (n=37) and IB (n=34) groups. Outcome measures included intra- and postoperative analgesic requirements, pain scores, and administration duration. Additional intraoperative analgesia was administered for a 10% increase in heart rate, while postoperative pain was assessed using the Children's and Infants Postoperative Pain Scale (CHIPPS), with scores >4 prompting supplementary analgesia. Monitoring extended for 24 hours post-surgery. Results: CB significantly reduced the need for intraoperative (p<0.001) and early postoperative (p=0.008) analgesia compared to IB. Although the CB group exhibited a slightly higher but non-significant analgesic requirement on the ward. No clinically relevant side effects were observed in either group. Conclusion: Both CB and IB are effective and safe methods for providing regional analgesia during orchidopexy. CB demonstrated superior efficacy intraoperatively and in the early postoperative period, while IB may offer advantages in the later recovery phase. However, additional analgesia is often required for orchidopexy, particularly in outpatient settings.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

An analysis of the physical and chemical phenomena accompanying the electrical discharges was carried out, principal factors inactivating microorganisms is studied. Characteristic factors of an electric discharge in cavitation mode providing a synergistic effect when disinfecting water with a discharge and chemical reagents are identified in order of importance. As a result of the integral action of cavitation, the inactivation of bacteria is intensified both due to the emergence of chem-ically active particles and due to local shock waves, acoustic currents and ultraviolet radiation in the area of cavitating bubbles. The similarity of cavitation processes in water systems implemented by underwater electric discharges and with the ultrasound has been experimentally proved. The main advantage of electric discharge cavitation in comparison with ultrasonic one is the wide band of ultrasonic frequencies of radiation inherent in electric discharge, high intensity and power of cav-itation processes, and, accordingly, the possibility of a significant increase in the volume of the disinfected liquid. The study enable better understanding and prediction of the effects that occur during a high-voltage underwater electrical discharge and have a bactericidal effect.

Image-guided radiotherapy supported by surface guidance can help track lower lung lesion respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how skin respiratory motion magnitudes and correlations with lung lesion respiratory motion vary between different skin regions of interest (ROI). Four-dimensional Computed Tomography (4DCT) images provide information on both skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. Analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing lower lung lobe lesion, as well as respiratory motion correlations between nine ROIs and TS. The effects of gender and adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between ROIs in both respiratory motion magnitudes and correlations to TS have been detected. An overall negative correlation between ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. Respiratory magnitudes in regions without rib support tended to be larger for men than for women, but no differences in ROI-to-TS correlation between sexes have been detected. Described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

The supply chain has incorporated products by putting them into hair scarfs. This study introduces the use of mini chips in health and beauty products and can reduce fatigue through enhanced sleep patterns. The mini chip could be placed in the scarf and used as a prototype. RFID technology provides the supply chain with specific information that is used to identify products and make communication easier. (Muhammad, et. al. 2013) This paper presents a new tool herein referred to as a scarf prototype which is developed to analyse EMG (electromyogram), ECG (electrocardiography), EEG (electroencephalogram), and EOG (electro-oculogram) signals that focuses in the area of sleep disorders. The mini chips used can be used to determine a solution for sleep disruption by using automated analytics. This could lead to improvement in our understanding of sleep disruption and overall sleep physiology. Automated technology allows repeated measurements, evaluation of sleep patterns, and provide suggestions to improve a person’s quality of sleep. This analysis compares the use of polysomnography and the scarf prototype. The analytics provide models and shows correlation between variables, such as EMG, ECG, EEG, and EOG. This study shows that the results from the scarf prototype is just as reliable as the original method, polysomnography.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

Childhood obesity is a public health problem and most of the interventions are focused on healthy habits as reducing energy intake, avoiding a sedentary lifestyle and increasing physical activity. However, usually they are based in individual programs, with few structured interventions in health systems without satisfactory results. PinPo aims to carry out an integral intervention in children with obesity, as well as in their parents and caregivers, to get motivation to change towards healthy lifestyle habits. The program contains 9 educational grupal sessions directed by a multidisciplinary expert team. 10 boys and girls, and another group with 10 family members and/or caregivers participate in sessions during 90 min biweekly. Moreover, there is an individual adaptation depending on the severity and comorbidities. At the beginning and at the end of the program, an integral evaluation for health status is developed including anthropometric, nutritional, physical activity, and psychologist and analytical measurements. Finally, a satisfaction survey is carried out on the participants.In conclusion, the implementation of PinPo could offer to paediatric patients with obesity and their families, an integral intervention to treat obesity and its complications. So, there are expectations of achieving favorable results that also allow to optimize its effectiveness.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

This study aims to provide an understanding of the preferences of student tourists regarding service attributes related to domestic accommodation. To clarify how lodging firms formulate policies for the student travel market, a “Relative to an Identified Distribution” (RIDIT) analysis in which responses are treated as ordinal data instead of equally spaced data is performed to examine the Likert-scale data obtained from 296 university students in Taiwan. In our RIDIT analytical results, respondents’ preferences are sorted in a descending importance. Of the examined attributes, “Cleanliness of rooms” is the attribute most prioritized by the students, followed by “Located in a safe neighborhood/feeling safe in the room,” and “Close to scenic area for meeting the trip requirement.” The attribute least prioritized by the students is “Interaction with other guests.” This analysis provides conclusions that differ from those obtained through commonly used techniques including the arithmetic average and exploratory factor analysis. The preference rankings indicate that managers should focus on the most prioritized service attributes and implement the necessary measures to enhance their service quality and maximize customer satisfaction.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Climate change, increasing global food needs, and decreasing global resources brought a new era to human every-day live with a strong turn to circular economy and sustainability. Food packaging and preservation is an important global sector where enchanced research is carried out. New methods such as active packaging and chemical preservatives replacement are of major interest. Many researchers were published studies about active packaging films, replacement of chemical preservatives with natural originated extracts, and novel incorporation procedures. Sequentially to our and other scientists’ previous work, in this paper we present the results of the improvement which was achieved by incorporating the developed nanohybrid of natural-halloysite/carvacrol-extract, the pure natural carvacrol extract and the commonly used low-density-polyethylene. The well known corona-treatment procedure was employed to produced the optimum final film and the results shown that the low-density-polyethylene incorporated with natural-halloysite/carvacrol-extract nanohybrid and coated external with extra carvacrol extract exhibited aproximatelly 100% higher Young-Modulus values, slightly decreased ultimate strength by 20%, and almost stable elonation at break properties. The water-vapor and oxygen barrier increased by 40%. Finally, the antioxidant activity of the corrona-treated film increased by 28% compared to the similar but untreated product because of the lower release rate of the carvacrol.

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.

Nowadays the freedom to make choices is considered of vital importance for decision-makers. Researchers investigating the psychological effects of choice provided empirical evidence about the many advantages of choice (i.e., increased intrinsic motivation, greater perception of self-determination, better performance, and greater life satisfaction). However, more recent studies demonstrated the downsides of choice. When the decision task difficulty exceeds the natural cognitive resources of human mind, the possibility to choose becomes more a source of unhappiness and dissatisfaction than an opportunity for a greater well-being. We here discuss in a detailed fashion the main findings of research in psychology and consumer behavior showing the bright sides and the downsides of choice.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.

The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Therefore, this article provides a comprehensive review of the relationship between magnesium ions and tumors, the mechanisms by which magnesium ions regulate mitochondrial function, and the theoretical basis and prospects of magnesium ion regulation of mitochondrial function for tumor treatment. This review aims to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Abstract. Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

We present a case report of a 26-years-old female suffering from Coffin Siris Syndrome, who underwent orthodontic treatment and surgery to solve her malocclusion and improve her aes-thetics and functional occlusion. Methods: The presurgical phase involved multibracket self-ligating attachments, Damon prescription. The patient underwent maxillofacial surgery to correct the severe skeletal malocclusion and relocate the bone bases in the right relationship. The post-surgical orthodontic treatment was performed to complete the alignment. Results: The pa-tient improved her aesthetics and functional abilities. Conclusions: Syndromic patients can un-dergo orthodontictreatment if comorbidities and collaboration allow it. Support and collaboration of families and psychotherapists must be considered, but clinical cases of syndromic patients can be faced and solved. Obviously, each syndromic patient is considered unique, and the risk-benefit ratio must be correctly assessed for each one.

Background: The surgical approach to treating calcaneal fractures, specifically Sanders types II, III, and IV, is still a subject of controversy. The decision to opt for open reduction and internal fix-ation (ORIF) or minimally invasive osteosynthesis (MIOS) remains uncertain owing to varying complication rates. This study intends to examine each treatment’s pros and cons in relation to the incidence of complications. Methods: In this retrospective study, we examined 70 patients treated between January 2018 and September 2022: 50 received ORIF, and 20 underwent MIOS. We evaluated functional outcomes with the Maryland Foot Score and the Creighton-Nebraska Health Foundation Assessment Scale (CNHFAS). We also assessed the amount of anatomical restoration using Böhler’s and Gissane’s angles, determined by radiographic checks, and the frequency of postoperative complications. Results: A significant reduction in the risk of reinter-vention was observed in patients with high anesthetic risks, polytraumatized individuals, and those with comorbidities who underwent MIOS. The chi-square test analysis of postoperative complications highlighted no substantial differences between the ORIF and MIOS groups in rela-tion to tendinitis, chronic pain and swelling, algodystrophy, and surgical wound infections (p > 0.20 for all). Conclusion: ORIF is more suitable for patients who have high motor function re-quirements, a long-term activity schedule and can endure potential additional procedures. This preference is because ORIF provides better anatomical restoration and features a lower osteoar-thritis occurrence rate.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

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.

The main purpose of this work was to tests of form and size of fatigue wear of the top layer of oil gear pump wheel (3PW-BPF-24). The object of tests was operated during a determined number of hours at strictly controlled operational and environmental parameters. A microscope of focal differentiation by Alicona InfiniteFocus G4 (with Focus-Variation optical measuring technology) was used for an identification, measurement and description of noticed superficial defects, which resulted from the fatigue process of the top layer and an earlier thermochemical treatment. The work was finished with an analysis of obtained results (based on the analysis of 3D scans) and conclusions concerning about optimization of the thermal treatment. Taking into consideration the presented results (suggestions) in the technology of improving strength properties of gear wheels (of this type oil pumps) may render it possible to obtain an appropriate fatigue endurance of the top layer, i.e. a minimization of observed superficial defects.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p<0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p<0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p<0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated cost. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer associated thrombus and COVID, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope to maximize effectiveness while minimizing risks.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

The paper discusses the mechanism of montmorillonite structure alteration and bentonites properties modification (on the example of samples from clay deposit Taganka, Kazakhstan) due to the thermochemical treatment (treatment with inorganic acid solutions at different temperatures, concentrations and reaction times). With the use of the suit of methods certain processes were distinguished: transformation of montmorillonite structure, which appears in the leaching of interlayer and octahedral cations, protonation of the interlayer and OH groups at octahedral sheets. Changes in the structure of the 2:1 layer of montmorillonite and its interlayer result in significant changes in the properties – reduction of cation exchange capacity and an increase of specific surface area. The results of the work showed that bentonite clays retain a significant portion of its adsorption properties even after the long term and intense thermochemical treatment (6M HNO3, 60°C, 108 hours)

Photothermal therapy (PTT) can overcome cancer treatment resistance by enhancing cell membrane permeability, facilitating drug accumulation, and promoting drug release within the tumor tissue. Iron oxide nanoparticles (IONPs) have emerged as effective agents for PTT due to their unique properties and biocompatibility. Approved for the treatment of anemia, as MRI contrast agents, and as magnetic hyperthermia mediators, IONPs also offer excellent light-to-heat conversion and can be manipulated using external magnetic field for targeted accumulation in specific tissues. Optimizing parameters such as laser wavelength, power density, shape, size, iron oxidation state, functionalization, and concentration is crucial for IONPs effectiveness. In addition to PTT, IONPs enhance other cancer treatment modalities. They improve tumor oxygenation enhancing the efficacy of radiotherapy and photodynamic therapy. IONPs can also trigger ferroptosis, a programmed cell death pathway mediated by iron-dependent lipid peroxidation. Their magneto-mechanical effect can exert mechanical force on cancer cells to destroy tumors, minimizing damage to healthy tissues. This review outlines strategies for managing photothermal performance and PTT efficiency with iron oxide nanoparticles, as well as synergies with other cancer therapies.

Choice poetics is a formalist framework that seeks to capture the impacts choices have on player experiences within narrative games. Developed in part to support algorithmic generation of narrative choices, the theory includes a detailed analytical framework for understanding the impressions choice structures make by analyzing the relationships between options, outcomes, and player goals. The theory also emphasizes the need to account for players’ various modes of engagement, which vary both during play and between players. In this work, we illustrate the non-computational application of choice poetics to the analysis of three different choices, in order to further develop the theory and make it more accessible to others. We focus first on analyzing so-called false choices in the game “Mass Effect”, and show how they actually provide meaningfully different outcomes for players who are utilizing certain modes of engagement. Second, we use choice poetics to examine the central repeated choice in “Undertale”, and show how it can be used to contrast two different player types that will approach a choice differently. Finally, we give an example of fine-grained analysis using a choice from the game “Papers Please”, which breaks down options and their outcomes to illustrate how the choice pushes players towards complicity via the introduction of uncertainty. Through all of these examples, we hope to show the usefulness of choice poetics as a framework for understanding narrative choices, and to demonstrate concretely how one could productively apply it to choices ‘in the wild’.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

The blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gauging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic form of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%) which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

A new two-step method for developing a nanocomposite of polypropylene (PP) decorated with photocatalytically active TiO2 nanoparticles (nTiO2) is proposed. This method involves low-temperature plasma functionalization of polypropylene followed by ultrasound-assisted anchoring of nTiO2. The nanoparticles, polymeric substrate, and resultant nanocomposite were thoroughly characterized using nanoparticle tracking analysis (NTA), microscopic observations (SEM, TEM, EDX), spectroscopic investigations (XPS, FTIR), thermogravimetric analysis (TG/DTA), and water contact angle (WCA) measurements. The photocatalytic activity of the nanocomposites was evaluated through the degradation of methyl orange. The individual TiO2 nanoparticles ranged from 2-6 nm in size. Oxygen plasma treatment of PP generated surface functional groups (mainly -OH and -C=O), transforming the surface from hydrophobic to hydrophilic, which facilitated efficient deposition of nTiO2. Optimized plasma treatment and sonochemical deposition parameters resulted in an active photocatalytic nTiO2/PP system, degrading 80% of methyl orange under UVA irradiation in 200 minutes. The proposed approach is considered versatile for the functionalization of polymeric materials with photoactive nanoparticles and, in a broader perspective, can be utilized for the fabrication of self-cleaning surfaces.

We describe an interesting case report about a patient with hemophilia A with severe chronic elbow arthropathy who underwent multiple surgical because of his condition. We collected all the clinical and imaging findings, and we compared the decision-making flow chart and the surgery performed with the most recent indications, treatments and complications reported in the literature. The aim of this case report is to show how usually the hemophilic patient even if young usually comes to our attention from the beginning with complex and advance musculoskeletal disease. Elbow hemophilic arthropathy is a complex disease and the management in these patients could be more difficult than others because of the higher risk of complications rate after all surgical procedures, for this reason it’s very important to treat these patients in hub centers with expertise in well-coordinated multidisciplinary teams. The path from diagnosis to surgical treatment of hemophilic elbow arthropathy can be a risky one, as it happened in this case.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

The per capita availability of freshwater resources on a global scale is gradually decreasing due to population growth, rapid urbanization, industrialization, and modern lifestyles. In this situation, wastewater management becomes a major concern. Conventional treatment processes used to treat wastewater discharges are not adequate for the advanced removal of pollutants, especially refractory organic pollutants, which are mainly organic compounds that are not easily biodegradable in the environment. The use of photocatalytic membrane reactors (PMRs) for tertiary wastewater treatment has attracted much interest in recent periods, and various configurations have been investigated. The performance of a PMR using an iron doped titanium photo catalyst and Polysulfone-based polymeric membrane for municipal wastewater treatment was evaluated under natural and simulated solar light. Obtained results proved that solar driven PMRs can remove organic loading (COD) with high efficiencies and may represent a suitable alternative for the tertiary treatment step of municipal wastewater.

This retrospective study aimed to evaluate the performance of the hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows who received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) <3.75 after treatment and loose-housing cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.

Taeniid infections pose a significant threat to both animal and public health, as certain tapeworms within this group can also infect humans, potentially leading to severe health conditions. Therefore, this calls for preventive and control measures, such as regular deworming of dogs. While the efficacy of deworming has been established in developed countries, there is a paucity of reported deworming practices in rural areas of developing countries, such as Tanzania. This study aims to understand determinants for helminth treatment-seeking behavior towards control of cestodial taeniid infections in rural settings in northern Tanzania. A cross-sectional study was undertaken in agropastoral and pastoral areas of northern Tanzania. Comprehensive data from household surveys in selected sub-villages were collected to ascertain dog ownership, dog deworming practices, and the availability of dewormers. Analytical methods were employed to discern how various determinants influenced deworming practices among dog owners in these communities. Awareness of dewormers specifically formulated for dogs emerged as a pivotal factor affecting dog deworming practices. Dog owners who were informed about appropriate dog dewormers were nearly two times more likely to engage in deworming compared to those with limited knowledge (OR = 1.78, 95% CI 1.77 - 4.18, p < 0.001). A majority 32(51.6%, 95% CI: 38.7-64.3) acknowledged accessing dewormers for livestock within their wards. Praziquantel a potent dewormer on cestodes was least known to most dog owners 2(13%, 95% CI: 2.3-41.6). Praziquantel, a potent and common dewormer effective against cestodial taeniid infections, remains relatively unknown in rural areas of northern Tanzania. Therefore, more awareness on appropriate deworming agents against taeniids in dogs should be raised in rural dog-keeping communities.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Given that metabolic syndrome, along with obesity as one of its key components, remains one of the leading yet insufficiently addressed public health issues, what contributes to the development and maintenance of the disorder must certainly attract the attention of professionals and scientists. Precisely because of this phenomenon, eating patterns associated with metabolic syndrome should be studied and attempts should be made to uncover patterns in occurrence. The aim of this study is to review the literature and consider the connection between metabolic syndrome and eating patterns such as emotional and compulsive eating, as well as through the lens of food addiction. Furthermore, we have attempted to uncover the role of psychiatry and psychotherapy in the treatment of metabolic syndrome and delve into the complexity of recognizing these patterns and emphasize the importance of a multidisciplinary approach in the treatment of metabolic syndrome.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

With growing city tourism, there is an increasing need for urban travel demand models to consider traffic generated by visitors. Existing research has concentrated on socio-demographic and journey-related factors to determine what influences the mode choice of tourists. In contrast, revealed preference data, like travel time, is almost never considered. In this article, we present the results of discrete choice modeling of city tourists’ mode choice based on revealed preference data from a survey we conducted in Kassel, Germany. We used multinomial logit models and determined the model parameters using maximum likelihood estimations. Surprisingly, travel time played a smaller role in mode choice than understood from previously established knowledge about everyday mobility. In the final model, travel time was only significant for the alternative walking. Also, most other sociodemographic and journey-related variables showed no significant influence. The final model reproduced the mode choice, but the goodness of fit was lower than expected from other research. We conclude that modeling the travel behavior of tourists is more complex than everyday mobility. An alternative approach that we suggest would be to model trip chains rather than single trips.

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Sustainability has become increasingly important. Existing project management methodologies are underdeveloped in sustainability. PM² is a methodology developed by the European Commission that aims to provide solutions and benefits to organizations. However, it doesn't include sustainability in its guide, because it aims to be generic. PRiSMTM aims to make the project management process more sustainable, it is based on the P5™ standard that aims to align portfolios, programmes and projects with sustainability. The major difference between the two methodologies is their main objectives. PRiSMTM has P5 Impact Analysis and Sustainability Management Plan as the main differentiating deliverable compared to other approaches, including PM². The most cited characteristic of PM² was to include best practices from other bodies of knowledge, and in PRiSMTM and P5™, it was to be an extension of the Triple Bottom Line, as it also includes product and process. The CEO of the PM² Alliance believes that PM² aims to be generic and usable for any project, so a focus on sustainability would remove the "elasticity" of the methodology. However, users wishing to use PM² and consider sustainability can include it in the additional objectives and use the P5 Impact Analysis and Sustainability Management Plan.

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation.

Researchers are increasingly concerned about microplastics (MPs) since they have proven to be detrimental to the environment and humans. They not only contribute to the accumulation of plastics in the environment, but they can also help spread micropollutants through absorption. MPs have entered the environment through a variety of channels, including direct discharge through human activities, the textile industry, and wastewater treatment systems. Wastewater treatment plants (WWTPs) are seen as the final line of defense, forming a barrier between MPs and the environment. The most common MPs found in wastewater are polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), and polystyrene. The purpose of this study is to investigate and measure the efficacy of conventional and advanced technologies in removing microplastic. The fate of MPs in WWTPs and their impact on various wastewater treatment processes will be thoroughly examined. Both conventional and advanced methods of treatment will be discussed. Conventional methods include coagulation/flocculation, sedimentation, and filtration. Advanced treatment methods that will be discussed include membrane bioreactors, rapid sand filtration, electrocoagulation, and photocatalytic degradation. Despite the high removal of MPs, WWTPs remain an important entry point into aquatic and terrestrial systems due to the large volumes involved and the quantity of sludge reused through land application. Also, the complex interactions between MPs and other environmental pollutants may broaden MPs' effects on wastewater treatment processes, which have yet to be fully researched. Furthermore, potential issues with MP removal from treatment procedures and microplastic remediation techniques in drinking water was discussed.

This study investigates the influence of expectations and trust on farmers' decisions regarding contractual choices in land transfer. The dataset used for analysis consists of 1101 households in Guizhou Province. The research focuses on two aspects: the selection between written and oral contracts, and the decision to continue the contractual relationship. The findings reveal that farmers' choices are significantly affected by their expectations and levels of trust.Specifically, when farmers' expectations regarding the land transfer process are not met, they tend to prefer written contracts over oral ones. This preference can be attributed to the greater clarity and risk reduction offered by written contracts. On the other hand, higher levels of trust increase the likelihood of farmers continuing the land transfer contract, as trust fosters a sense of confidence and security in the ongoing relationship.Interestingly, trust also plays a moderating role. Farmers who have aligned expectations and high levels of trust are more inclined to opt for oral contracts. This preference for oral contracts can be attributed to their flexibility and emphasis on interpersonal relationships, allowing for better adaptation to the changing dynamics of land transfer.These findings contribute to a deeper understanding of the factors influencing farmers' decision-making processes regarding contractual choices in land transfer. They provide valuable insights for policymakers involved in land transfer, enabling them to optimize policies and facilitate farmers' decision-making processes.

Electric vehicles (EVs) play a significant role in reducing carbon emissions. In the US, EVs are mostly owned by multi-vehicle households, and their usage is primarily studied in the context of vehicle miles traveled. This study takes a unique approach by analyzing EV usage through the lens of vehicle choice (between EVs and internal combustion engine vehicles) within multi-vehicle households. A two-step machine-learning framework (clustering and decision trees) is proposed. The framework determines the preferred trip category for EV use and captures the effects of household attributes, driver attributes, built-environment factors, and gas prices on EV use in multi-vehicle households. Results indicate that discretionary trips (accumulated local effect = 0.037) are mostly preferred for EV use. EV preference is more pronounced among households with fewer workers (<2) and lower income levels. These findings are valuable for policymakers and auto manufacturers in targeting specific market segments and promoting EV adoption.

Lignocellulosic biomass has garnered attention as an abundant and sustainable alternative energy source that can facilitate reliable and environmentally friendly energy generation. Energy security improves, and environmental impacts diminish when bioethanol, a biofuel produced via lignocellulose-based processes, is utilized. The lignocellulosic biomass of Thysanolaena latifolia has considerable potential as a bioethanol feedstock due to its high carbohydrate content (62.4 ± 0.7%). In this study, feedstock derived from T. latifolia was pretreated with various concentrations of H3PO4 to determine the ideal conditions for enzymatic hydrolysis to convert the feedstock to fermentable sugar. The findings revealed that hydrolysis efficiency and glucose recovery yields were substantially improved compared to those of the untreated sample. Pretreated samples were enzymatically digested to produce a liquid hydrolysate. This hydrolysate was fermented without detoxification using Saccharomyces cerevisiae TISTR 5339 to produce ethanol. The results indicated that T. latifolia biomass hydrolysate is a promising long-term carbon source for ethanol production from cellulosic biomass. Furthermore, the morphological and crystallographic characteristics of the treated T. latifolia biomass were influenced by H3PO4 concentration, as indicated by the SEM images, X-ray diffractogram patterns, and crystallinity index values. Therefore, utilizing T. latifolia feedstock to produce bioethanol can enhance bioenergy sustainability.

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

Abstract Background: Occipital neuralgia is a debilitating condition and traditional treatments often provide limited or temporary relief. Recently, ultrasound-guided hydrodissection of the greater occipital nerve (GON) has emerged as a promising minimally invasive approach. Objectives: To describe two novel ultrasound-guided hydrodissection with 5% dextrose for GON and discuss their advantages, disadvantages, and considerations. Methods: Two case reports are presented. Case 1 describes a lateral decubitus approach for hydrodissecting the GON between the semispinalis capitis (SSC) and obliquus capitis inferior (OCI) muscles. Case 2 details a cranial-to-caudal approach for hydrodissecting the GON within the SSC and upper trapezius (UT) muscles when the GON pass through these two muscles. Results: Both patients experienced significant and sustained pain relief with improvements in function and quality of life. Conclusions: Ultrasound-guided GON hydrodissection using 5% dextrose is a promising treatment for occipital neuralgia. The lateral decubitus and cranial to caudal approaches provide additional options to address patient-specific anatomical considerations and preferences.

Introduction: Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics remains relevant. The aim of the study: to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae in the complex therapy of colorectal cancer (CRC) in the early postoperative period. Materials and methods: A total of 36 patients diagnosed with CRC were enrolled in the study. The study group (Group A) comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group (Group C) included 12 CRC patients without autoprobiotic therapy.Prior to surgery and between days 14-16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complains analysis. examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), analysis of interleukins in serum. Results: The use of autoprobiotics led to decrease dyspeptic complaints after surgery, was associated with absence of postoperative complications, did not cause side effects, led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra, Fusobacterium nucleatum, decrease in the quantitative content of Clostridium perfringens, Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The administration of autoprobiotics in the postoperative period is highly effective and safe in the comprehensive treatment of colorectal cancer patients. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine and neural systems.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curable for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists or/and to downstage patients who are beyond Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine Kinase Inhibitors (TKIs) can be used as a bridging systemic therapy to LT in patients with contraindication to locoregional liver-directed therapies. Immune Checkpoint Inhibitors (ICIs) treatment can be utilized either as a monotherapy or as a combination therapy with Bevacizumab or TKIs prior to LT. Acute rejection post liver transplantation is a concern in the context of ICIs treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Low fertility is a critical social problem worldwide, and infertility has a prevalence of 15%. This cross-sectional study aimed to understand the factors affecting the usage and satisfaction of Korean medicine (KM) in subfertile women. An online survey was conducted from November 3 to November 8, 2021. The survey collected basic information, KM treatment experience, and satisfaction from women who experienced poor pregnancy. The t-test and chi-square test (χ2-test) were used to determine the overall characteristics of the subjects and factors affecting the utilization and satisfaction of KM treatment. Of the total of 29,465 people, 4,922 read the survey email, and 601 responded. After excluding 51 insincere respondents, 550 respondents were included in the final analysis. Of these, 43.1% had experience with conventional treatment, and 15.6% had received KM treatment. Integrative subfertility treatment was significantly more common (24.9%) than KM treatment alone (10.2%) (P=0.00). Women with no childbirth experience (P=0.01) and those with a master’s degree (P=0.01) were more willing to participate in the ‘KM Support Project for Subfertility’. Our findings suggest that subfertile patients prefer integrated medical treatment over KM alone. Further studies are needed to assess the status of integrative medicine treatment, satisfaction with each KM intervention, factors for low satisfaction, and patient requirements.

This paper examines the importance of choice of cooking fuels in wellbeing, analysing relationships between the proportion of population with primary reliance on different types of fuels for cooking (predictor variable), and key wellbeing indices (outcome variables) - Personal Health, Social Life, Civic Engagement, Life Evaluation, Negative Experience. By combining two global datasets from Gallup and WHO, the study adds to current evidence by taking a global perspective. Controlling for demographic factors such as income per capita, age, education level, employment, etc., regression modelling of these relationships show that clean cooking fuels are influential in all of the key wellbeing indices with the exception of the Life Evaluation Index. Among the key wellbeing indices, Personal Health and Negative Experience Indices are the most strongly influenced by choice of clean cooking fuels. By adding access to electricity as an additional predictor variable, the analysis highlights the potential for integrating eCooking into national electrification plans as part of sustainable energy transitions, given that health outcomes (Personal health and Negative experience indices) appear to be as closely linked to choice of cooking fuels as to access to electricity.

The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. Since then, ongoing mutational dynamics have led to the formation of antigenic clusters, prompting the World Health Organization to advocate for regular updates to H3N2 vaccines. Research in the Western Pacific region underscores the necessity for heightened awareness and effective control strategies. Stemming from avian influenza A, the 1968 H3N2 influenza pandemic resulted in the deaths of one million people globally, with its seasonal variants primarily affecting older individuals and causing severe illness due to antigenic drift. To address the challenge of vaccine efficacy against H3N2 mutations, researchers are exploring innovative strategies such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. This review comprehensively examines various aspects of the Influenza A (H3N2) virus, encompassing its virological characteristics, evolutionary trends, global epidemiology, vaccination strategies, antiviral interventions, and emerging diagnostic approaches. It underscores the impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, pandemic potential, and the interplay between viral factors and host immune responses. Moreover, the review evaluates antiviral therapies and the issue of drug resistance, emphasising the necessity for multidisciplinary approaches involving researchers, healthcare professionals, and policymakers to comprehend H3N2 and enhance public health interventions.