Defining the Soluble and Extracellular Vesicle Protein Compartments of Plasma Using In-Depth Mass Spectrometry-Based Proteomics.

Plasma-derived extracellular vesicles (pEVs) are a potential source of diseased biomarker proteins. However, characterizing the pEV proteome is challenging due to its relatively low abundance and difficulties in enrichment. This study presents a streamlined workflow to identify EV proteins from cancer patient plasma using minimal sample input. Starting with 400 µL of plasma, we generated a comprehensive pEV proteome using size exclusion chromatography (SEC) combined with HiRIEF prefractionation-based mass spectrometry (MS). First, we compared the performance of HiRIEF and long gradient MS workflows using control pEVs, quantifying 2076 proteins with HiRIEF. In a proof-of-concept study, we applied SEC-HiRIEF-MS to a small cohort (12) of metastatic lung adenocarcinoma (LUAD) and malignant melanoma (MM) patients. We also analyzed plasma samples from the same patients to study the relationship between plasma and pEV proteomes. We identified and quantified 1583 proteins in cancer pEVs and 1468 proteins in plasma across all samples. While there was substantial overlap, the pEV proteome included several unique EV markers and cancer-related proteins. Differential analysis revealed 30 DEPs in LUAD vs the MM group, highlighting the potential of pEVs as biomarkers. This work demonstrates the utility of a prefractionation-based MS for comprehensive pEV proteomics and EV biomarker discovery. Data are available via ProteomeXchange with the identifiers PXD039338 and PXD038528.

Identification and optimization of pyridine carboxamide-based scaffold as a drug lead for Mycobacterium tuberculosis.

New drugs with novel mechanisms of action are urgently needed to tackle the issue of drug-resistant tuberculosis. Here, we have performed phenotypic screening using the Pathogen Box library obtained from the Medicines for Malaria Venture against Mycobacterium tuberculosis in vitro. We have identified a pyridine carboxamide derivative, MMV687254, as a promising hit. This molecule is specifically active against M. tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) but inactive against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli pathogens. We demonstrate that MMV687254 inhibits M. tuberculosis growth in liquid cultures in a bacteriostatic manner. Surprisingly, MMV687254 was as active as isoniazid in macrophages and inhibited M. tuberculosis growth in a bactericidal manner. Mechanistic studies revealed that MMV687254 is a prodrug and that its anti-mycobacterial activity requires AmiC-dependent hydrolysis. We further demonstrate that MMV687254 inhibits M. tuberculosis growth in macrophages by inducing autophagy. In the present study, we have also carried out a detailed structure-activity relationship study and identified a promising novel lead candidate. The identified novel series of compounds also showed activity against drug-resistant M. bovis BCG and M. tuberculosis clinical strains. Finally, we demonstrate that in contrast to MMV687254, the lead molecule was able to inhibit M. tuberculosis growth in a chronic mouse model of infection. Taken together, we have identified a novel lead molecule with a dual mechanism of action that can be further optimized to design more potent anti-tubercular agents.

Capturing of neurotoxins causing diabetes stress and nervous breakdown in the aqueous medium by naphthazarin esters.

The fear of an increase in blood sugar can be very traumatic. Being diabetic either type I or type II leads to a disorder called diabetes distress having traits of stress, depression, and anxiety. Among risk factors of diabetes mellitus heavy and trace metal toxicity emerges as new risk factors reported in many studies. In this study we target toxic metals, viz., Ni2+, Zn2+, and Cu2+, involved in the pathogenesis of diabetes and diabetic stress with naphthazarin esters. The compounds C1-C3 isolated from the leaves and roots of Arnebia guttata were tested for their metal-binding ability in an aqueous medium in UV-Visible and nuclear magnetic resonance (NMR) studies. These probes are well-known naphthoquinones present in the Arnebia species. In the UV-Visible titrations of compounds C1-C3 with Na2+, K2+, Zn2+, Ca2+, Cu2+, Mg2+, Co2+, and Ni2+ ions, significant binding was observed with Ni2+, Cu2+, and Zn2+ ions in MeOH/H2O. There occurs a beautiful formation of red-shifted bands between the 520 to 620 nm range with a synergistic increase in absorbance. Also, the disappearance of proton peaks in the 1H NMR spectrum on addition of metal ions confirmed binding. Compounds C1-C3 isolated from A. guttata came out as potent Ni2+, Zn2+, and Cu2+ sensors that are reportedly involved in islet function and induction of diabetes.

Impact of Virtual Reality on Pain, ROM, Muscle Strength and Quality of Life among Breast Cancer Patients: An Integrative Review of Literature.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women globally, with significant impacts on physical, emotional, and functional well-being. Traditional rehabilitation methods may not fully address the multifaceted challenges faced by breast cancer survivors (BCSs), prompting exploration into innovative approaches such as Virtual Reality (VR) technology. OBJECTIVE: The present review aims to assess the effectiveness of VR in alleviating pain, improving Range of Motion (ROM), enhancing muscle strength, and augmenting the overall quality of life in patients undergoing breast cancer rehabilitation. METHODS: A comprehensive review of existing literature was conducted, focusing on studies investigating the use of VR in breast cancer rehabilitation. PubMed, Scopus, PEDro and Google scholar were searched for articles addressing VR interventions targeting pain management, ROM improvement, muscle strength enhancement, and quality of life enhancement in breast cancer patients. RESULTS: Findings yielded total 12 articles matching the selection criteria. VR technology has shown promising results in addressing the multifaceted needs of breast cancer patients. VR also serves as a distraction tool, positively impacting psychological well-being and mitigating negative psychological symptoms associated with the disease. CONCLUSION: VR represents a non-pharmacological approach to pain management and rehabilitation in breast cancer patients. Its ability to engage emotional, cognitive, and attention processes contributes to its effectiveness in enhancing overall quality of life. Further research is warranted to elucidate the long-term benefits and optimal utilization of VR technology in breast cancer rehabilitation programs.

Optimizing wastewater treatment through artificial intelligence: recent advances and future prospects.

Artificial intelligence (AI) is increasingly being applied to wastewater treatment to enhance efficiency, improve processes, and optimize resource utilization. This review focuses on objectives, advantages, outputs, and major findings of various AI models in the three key aspects: the prediction of removal efficiency for both organic and inorganic pollutants, real-time monitoring of essential water quality parameters (such as pH, COD, BOD, turbidity, TDS, and conductivity), and fault detection in the processes and equipment integral to wastewater treatment. The prediction accuracy (R2 value) of AI technologies for pollutant removal has been reported to vary between 0.64 and 1.00. A critical aspect explored in this review is the cost-effectiveness of implementing AI systems in wastewater treatment. Numerous countries and municipalities are actively engaging in pilot projects and demonstrations to assess the feasibility and effectiveness of AI applications in wastewater treatment. Notably, the review highlights successful outcomes from these initiatives across diverse geographical contexts, showcasing the adaptability and positive impact of AI in revolutionizing wastewater treatment on a global scale. Further, insights on the ethical considerations and potential future directions for the use of AI in wastewater treatment plants have also been provided.

A Rare Case of Broad Ligament Hematoma Following Vaginal Delivery.

This case report explores a rare complication of broad ligament hematoma post-vaginal delivery, emphasizing the importance of prompt intervention in cases of postpartum hemorrhage with atypical presentations. A 22-year-old primigravida, at 39 weeks with hypothyroidism, presented with intermittent abdominal pain and normal fetal movements. After a normal vaginal delivery with a right mediolateral episiotomy, she developed intense perineal pain and hypotension due to a broad ligament hematoma. The surgical intervention included the evacuation of the hematoma, laparotomy, and internal iliac artery ligation. The postoperative care involved treatment for a methicillin-resistant Staphylococcus aureus (MRSA) infection, and the patient received blood transfusions. The follow-up showed complete wound healing and an uneventful postnatal period, with the patient resuming normal activities after three weeks. Comparison with similar cases in the literature highlighted various etiologies and clinical presentations of broad ligament hematoma, ranging from broad ligament pregnancy to uterine perforation. Timely surgical exploration, hematoma evacuation, and arterial ligation were essential in preventing adverse maternal outcomes, underscoring the importance of multidisciplinary collaboration and vigilant postoperative monitoring. The report emphasizes the need for a high index of suspicion and prompt intervention to ensure optimal recovery and minimize complications in cases of broad ligament hematoma following vaginal delivery.

Efficacy of auxin-inducible protein degradation in C. elegans tissues using different auxins and TIR1-expressing strains.

The auxin-inducible degradation system has emerged as a powerful tool to deplete proteins of interest in cells and tissues of various model organisms, including C. elegans 2-5 . Here, we present a detailed protocol to perform AID-driven spatiotemporal depletion of specific proteins in C. elegans tissues. First, we introduced the AID degron and a fluorescent reporter at two conserved proteins: (a) the transcription factor CFI-1 (human ARID3), which is expressed in the nucleus of multiple C. elegans neurons and head muscle cells 6,7 , and (b) the broadly expressed translation initiation factor Y47D3A.21 (human DENR) that localizes in the cytoplasm. Second, we provide a step-by-step guide on how to generate C. elegans strains suitable for AID-mediated protein (CFI-1 and DENR) depletion. Third, we find that the degree of CFI-1 and DENR depletion in C. elegans tissues is comparable upon treatment with either natural auxin (indole-3-acetic acid (IAA) or a water-soluble synthetic auxin analog (K-NAA). Last, we compare the degree of AID-mediated CFI-1 depletion in C. elegans neurons when the transport inhibitor response 1 (TIR1), component of the SCF ubiquitin ligase complex, is provided in neurons or all somatic cells. Altogether, this protocol provides side-by-side comparisons of different auxins and TIR1-expressing lines. Such comparisons may benefit future studies of AID-mediated protein depletion in C. elegans . Graphical abstract: Image provided as pdf (together with Figures). Highlights: Efficient protein depletion in C. elegans tissues upon treatment with either natural or synthetic auxins. Pansomatic TIR1 expression leads to efficient depletion of CFI-1 and DENR.Panneuronal TIR1 expression leads to neuron-specific, yet variable CFI-1 depletion.The AID system is compatible with fluorescence microscopy, Western blotting and behavioral assays.

Protocol for auxin-inducible protein degradation in C. elegans using different auxins and TIR1-expressing strains.

The auxin-inducible degron (AID) system is a powerful tool to deplete proteins in vivo. Here, we present a protocol for AID-mediated depletion of two proteins (CFI-1/AT-rich interaction domain 3 [ARID3] and Y47D3A.21/density-regulated re-initiation and release factor [DENR]) in C. elegans tissues using different auxins and transport inhibitor response 1 (TIR1)-expressing strains. We describe steps for genetic crossing, sample preparation, fluorescent microscopy, and treatment with either natural (indole-3-acetic acid [IAA]) or synthetic (1-naphthaleneacetic acid, potassium salt [K-NAA]) auxins. We then detail procedures for comparing the degree of CFI-1 depletion in C. elegans neurons upon panneuronal or pansomatic TIR1 expression. For complete details on the use and execution of this protocol, please refer to Li et al.1,2.

Chest Physiotherapy Interventions for Children During SARS-COV-2 Pandemic.

Since the first case of Severe Acute Respiratory Syndrome Coronavirus-2/Coronavirus Disease 2019 (SARS-COV-2/COVID-19) was discovered in Wuhan, China, it spread to vast limits globally and became a public health disaster, affecting nearly all countries around the globe. Along with mainstream medical treatment, alternative medicine desperately was the need of the hour for youngsters to manage their symptoms while being self-quarantined and ultimately to improve their chances of survival and recovery from COVID-19. Since the beginning of SARS-COV-2, few studies address the clinical-functional presentation of viral infection and management with physiotherapy for children. Major online electronic databases PubMed, PEDro, and Google Scholar were researched to identify, organize and commission the current review. To create a search strategy, Medical Subject Headings and Descriptors of Science and Health were utilized. The authors looked for other studies by screening the references list of the potentially pertinent papers. These computerized searches turned up studies and those studies' bibliographies with pertinent citations were examined. Personal protective equipment was a crucial component for protection and contact precaution. Following hypoxia, effective oxygen therapy is administered right away. When necessary, under the right circumstances, nasal high-flow oxygen therapy, non-invasive ventilation, lung-protective breathing methods, and prone positioning can be used. Children with SARS-CoV-2/COVID-19 may benefit from physiotherapy interventions with a focus on ventilatory management, airway clearance procedures, early activities, and mobilization.

Wheatgrass (Triticum Aestivum) Extract Loaded Chitosan Solid Lipid Nanoparticles: Formulation, Physicochemical Characterisation and Cytotoxic Potential.

BACKGROUND: The prevalence of cancer is around the world, and is identified as a multifarious ailment. Amongst the most common reasons for cancer in the world is oxidative stress, and this can be overcome by taking the herbal plant wheatgrass in any form. AIM AND OBJECTIVE: The aim of the present work is to formulate wheatgrass extract-loaded solid lipid nanoparticles using Box-Behnken design and to investigate the effect of formulation variables. METHODS: Using the hot homogenisation method, the current work plan aimed to develop wheatgrassfilled chitosan solid lipid nanoparticles by means of a Box-Behnken design. This study investigated the effect of three formulation variables on particle size and entrapment efficiency, namely the sodium alginate concentration, the chitosan concentration, and the sonication time. Extraction of wheatgrass was done in a soxhlet extractor, using methanolic extract. Furthermore, the authors have examined recent patents associated with wheatgrass to enhance their comprehension of this herbal plant. RESULTS: The hot homogenisation technique was used to prepare Triticum aestivum extract loaded with solid lipid nanoparticles (SLNs). For BBD, all formulations were analysed for particle size, which ranged from 394.4 to 911.2 nm, and for polydispersity index, which ranged from 0.527 to 1.0. Batch code BB SLN-8 was found to be the finest suitable because of a maximum loading capacity of 58.23 ±0.11 % (w/w), maximum entrapment efficiency of 55.12±0.17 % (w/w), and minimum particle size of 394.4nm by using sodium alginate as a surface stabiliser at sonication time ~ 10 min and having maximum percentage yield of 49.87%. During characterisation studies and MCF-6 cell line studies, it was found that wheatgrass has antioxidant potential and is potent against breast cancer. CONCLUSION: As an alternative medicine for cancer, wheatgrass is considered to be effective due to its high antioxidant content.

Deciphering the crystal structure of a novel nanobody against the NEIL1 DNA glycosylase.

Nanobodies (VHHs) are single-domain antibodies with three antigenic CDR regions and are used in diverse scientific applications. Here, an ∼14 kDa nanobody (A5) specific for the endonuclease VIII (Nei)-like 1 or NEIL1 DNA glycosylase involved in the first step of the base-excision repair pathway was crystallized and its structure was determined to 2.1 Šresolution. The crystals posed challenges due to potential twinning and anisotropic diffraction. Despite inconclusive twinning indicators, reprocessing in an orthorhombic setting and molecular replacement in space group P21212 enabled the successful modeling of 96% of residues in the asymmetric unit, with final Rwork and Rfree values of 0.199 and 0.229, respectively.

Reduced expression of Ankyrin-G and E-cadherin in duodenal mucosal biopsy of subjects with celiac disease.

Confirmatory diagnosis of celiac disease (CD) include histopathology of duodenal biopsy and tissue trans-glutaminase-IgA. Identification of tissue-specific histological markers is warranted to improve the diagnosis. A genetic study in CD identified the association of ankyrin-G that connects E-cadherin with ß2-spectrin in epithelial cells of the duodenal tissue. We attempted to investigate the differential expression of ankyrin-G, E-cadherin and ß2-spectrin in duodenal biopsy of CD subjects compared to non-CD controls. Duodenal tissue was collected from 83 study participants, of which 50 were CD, and 33 were non-CD controls. Whole RNA was isolated from 32 CD and 23 non-CD controls from available tissues, and differential mRNA expression was measured using real-time PCR. Tissue sections from 18 CD cases and 10 non-CD controls were immunostained using monoclonal antibodies. Tissue immunohistochemistry were evaluated for differential expression and pattern of expression. RT-PCR revealed significantly reduced expression of ankyrin-G (fold change=0.63; p=0.03) and E-cadherin (fold change=0.50; p=0.02) among CD subjects compared to non-CD controls. Tissue immunohistochemistry confirmed the reduced expression of ankyrin-G and E-cadherin in CD. Differential expression is grossly limited within the outer columnar epithelial cell layer. Expression fold change of E-cadherin was seen to partially correlate with the serum tTG level (r=0.4; p=0.04). In CD, reduced expression of two key cytoskeletal proteins (ankyrin-G and E-cadherin) in duodenum mucosa was observed, which indicates its implication in disease biology and could be tested as a tissue-specific biomarker for CD. Functional studies may unravel the specific contribution of these proteins in CD pathophysiology.

Noninvasive neuromodulatory effect on cognition in individuals with traumatic brain injury: A single-blinded, two-arm parallel randomized clinical trial.

Objectives: The study aimed to compare the effect of cranial electrical stimulation (CES) and transcranial direct current stimulation (tDCS) in improving cognition among individuals with mild traumatic brain injury. Patients and methods: The pretest-posttest randomized controlled study was conducted between November 2020 and March 2022. Seventy-two patients (64 males, 8 females; mean age: 40.5±9.5 years; range, 18 to 45 years) experiencing cognitive impairment within three months of traumatic brain injury were recruited. Participants were randomly assigned into two groups: Group 1 (CES with cognitive training, n=36) and Group 2 (tDCS with cognitive training, n=36). Participants were blinded in the study. Both groups received 30-min sessions of neuromodulation along with 30 min of cognitive training five days a week for four weeks. The patients were assessed at baseline and at the end of two and four weeks of intervention. The primary outcome measure was the Montreal Cognition Assessment (MoCA), and the secondary outcome measure was the Galveston Orientation Amnesia Test (GOAT). Results: Demographic and baseline characteristics depicted normal distribution for both groups (p>0.05). Within group analyses of both groups demonstrated significant differences for both outcome measures (MoCA: p=0.001; GOAT: p=0.001). Between group analyses of MoCA showed significant improvement with p-value of 0.001 while GOAT exhibited p-value of 0.002 showing significant difference between the two groups. Time group interaction effect and covariance analyses depicted significant improvement with p-value of 0.001 for both outcome measures with excellent effect size >0.80. Conclusion: Cranial electrical stimulation was a more effective noninvasive neuromodulatory device than tDCS in improving cognition among individuals with traumatic brain injury.

Zuranolone, a neuroactive drug, used in the treatment of postpartum depression by modulation of GABAA receptors.

BACKGROUND: Postpartum depression [PPD] is a prevalent and debilitating mood disorder that affects mothers in the weeks to months after childbirth. Zuranolone (Zurzuvae) is a novel pharmaceutical agent that was approved by the US FDA on 4 August 2023 for the management of PPD. This review article provides a comprehensive overview of zuranolone, focusing on its dosing, chemistry, mechanism of action, clinical trials, adverse drug reaction, and overall conclusion regarding its utility in the management of PPD. It also discusses the recommended dosing strategies to achieve optimal efficacy while minimizing adverse effects as the dosage regimen of zuranolone is critical for its therapeutic application. Moreover, it gives insights into neurobiological pathways involved in PPD. METHODOLOGY: Data from randomized controlled trials and observational studies was collected to provide a comprehensive understanding of zuranolone in the management and treatment of PPD. CONCLUSION: Zuranolone represents a promising therapeutic option for women suffering from postpartum depression. However, ongoing research and post-marketing surveillance are essential to further elucidate its long-term safety and efficacy. The integration of zuranolone into clinical practice may significantly improve the quality of life for mothers facing the challenges of postpartum depression.

The combined effect of neuro-modulation and neuro-stimulation on pain in patients with cervical radiculopathy - a double-blinded, two-arm parallel randomized controlled trial.

INTRODUCTION: Cervical radiculopathy is one of those disabling conditions which results in central and peripheral pain and thus affects the quality of life. Transcutaneous Electrical Nerve Stimulation (TENS) and exercises produce analgesic effect but their long-term effect has not been available to date. Transcranial Direct Current stimulation (tDCS) is known to produce promising effects on central pain by targeting cortical activity. PURPOSE: To determine the combined effect of tDCS and TENS with exercises on pain and quality of life in patients with cervical radiculopathy. METHOD: Forty four patients (male: female = 26:18) of the age group 18-50 years were recruited and randomly allocated into the experimental group and control group. The experimental group received active anodal tDCS for 20 min with an intensity of 2 mA, while the control group received sham anodal tDCS. TENS over the pain distribution area for 20 min with 5 Hz intensity and 80-150 ms pulse duration followed by neck-specific exercises were given in both groups. This protocol was given 5 days a week for 4 weeks. Pre and post-assessments were obtained through outcome measures that the Numeric Pain Rating Scale and Neck Disability Index for the measurement of pain, functional disability, and quality of life. RESULT: Paired t-test/Wilcoxon-Signed Rank test, and Index and Mann-Whitney U test were used to compare the demographic variables within and across the groups, respectively for Neck Disability for Numeric Pain Rating Scale, keeping the P-value < 0.05 as significant. One-way repeated-measures analysis of variance (ANOVA) was applied to determine the between-subject factor differences. Post hoc tests with Bonferroni correction for repeated analyses were performed. Results depicted a significant effect for NDI (P = 0.001 for both groups) and NPRS (P = 0.003 for the experimental group and 0.007 for the control group). Significant Interaction effect (time*group) was observed for NDI (F = 42, 5382.77) and NPRS (F = 42, 1844.57) with a P-value of 0.001 for both outcome measures. Clinical significance was observed for both outcome measures having a mean difference in 50.21 and 4.57 for NDI and NPRS, respectively compared with the established MCID of 13.2 and 2.2 scores for respective outcome measures. CONCLUSION: It was concluded that active tDCS along with TENS and exercise intervention was effective on pain, disability, and quality of life in patients with cervical radiculopathy.

Facilitating Culturally Competent Breast Imaging Care in South Asian Patients.

South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations.

Enhancement of Wheat (Triticum aestivum L.) Growth and Yield Attributes in a Subtropical Humid Climate through Treated Ganga Sludge-based Organic Fertilizers.

BACKGROUND: Sewage sludge is a by-product of urbanization that poses environmental and health challenges. However, it can also be a valuable source of organic matter and nutrients for agriculture. METHOD: This study aimed to assess the potential of five types of organic fertilizers derived from treated Ganga sludge on the growth of wheat plants. The Patanjali Organic Research Institute has developed five types of granulated organic fertilizer from the stabilized Ganga sludge. RESULTS: The results showed that the organic fertilizers significantly improved the wheat performance in terms of plant height, biomass accumulation, chlorophyll content, leaf area and other yield parameters. Furthermore, the fertilizers ameliorated soil physicochemical attributes and augmented the availability of macro- and micronutrients. Importantly, levels of heavy metals in soil and wheat grains remained within permissible limits, affirming the safety and appropriateness of these fertilizers for wheat cultivation. CONCLUSION: This study underscores the efficient utilization of treated Ganga sludge as a valuable organic fertilizer source, proposing a sustainable and ecologically sound approach for sewage sludge management and enhancement of agricultural productivity.

Group tele-rehabilitation improves quality of life among subjects with Parkinson's disease: A two arm non-parallel non-randomized clinical trial.

INTRODUCTION: Tele-rehabilitation has lately emerged as a promising medium for increasing patient adherence with significant positive results. One of the most prevalent neurological diseases affecting movement is Parkinson's disease (PD), which causes a variety of motor and non-motor symptoms among patients. Consequentially, the study was designed to compare the efficacy of group tele-rehabilitation with individual tele-rehabilitation in improving quality of life (QoL) among subjects with PD. METHOD: A two-group pretest-posttest, non-randomized clinical study recruited 68 subjects and classified them into two groups, i.e., Group A (group therapy, n = 36) and Group B (individual therapy, n = 32). Groups A and B received a supervised protocol consisting of a 40-min session on alternate days/week for twelve weeks via the WhatsApp Messenger application through group and individual therapy, respectively. The Parkinson's disease questionnaire (PDQ-39), mental and physical components of the Short Form Survey (SF-12) were used as primary outcome variables, while the Satisfaction questionnaire was used as a secondary outcome variable. RESULT: The p-values related to within-group analyses were <0.05 except SF-12 PCS >0.05 in Group A and <0.05 in Group B. While the p-values related to between-group analyses were <0.05 except for pre-scores of SF-12 (MCS and PCS). The effect sizes for PDQ-39, SF-12 (MCS), and SF-12 (PCS) were -2.37, 3.36, and 0.66 in Group A and 1.95, 2.69, and 2.03 in Group B, respectively. CONCLUSION: The study concluded that group tele-rehabilitation is more effective in improving QoL among subjects with PD as compared to individual tele-rehabilitation. Clinical trial Registration NoCTRI/2022/04/041818.

Dietary Influences on Skin Health in Common Dermatological Disorders.

The role of diet in the development of skin disorders is well-established, with nutritional deficiency often identified as a risk factor for skin diseases. Imbalances in the skin can be caused by nutritional deficiencies, excessive intake, insufficient nutrients, and hazardous ingredients. Patients frequently inquire about the impact of dietary patterns on skin health when consulting dermatologists in clinical settings. Simultaneously, the popularity of using nutritional supplements containing vitamins, minerals, and nutraceutical blends has been on the rise. It is crucial for dermatologists, primary care physicians, and other healthcare providers to be acquainted with evidence-based dietary interventions, distinguishing them from those that are more market-driven than truly efficacious. This review explores the modification of diet, encompassing both dietary exclusion and supplementation, as a therapeutic approach for conditions such as psoriasis, atopic dermatitis, bullous disease, vitiligo, and alopecia areata. A comprehensive literature search, utilizing the PubMed/Medline, Google Scholar, and Medscape databases, was conducted to investigate the relationship between each nutrient and various inflammatory skin diseases. The findings emphasize the significance of a well-balanced and thoughtfully planned diet in supplying adequate amounts of proteins, vitamins, and minerals to support optimal skin health. Additionally, this comprehensive review navigates through various dietary recommendations, offering insights into their multifaceted impacts on the immune system, gut microbiome, and skin health. The goal is to pave the way for informed and targeted dietary interventions for individuals dealing with food allergies and associated skin conditions.

Multiple UDP glycosyltransferases modulate benzimidazole drug sensitivity in the nematode Caenorhabditis elegans in an additive manner.

Xenobiotic biotransformation is an important modulator of anthelmintic drug potency and a potential mechanism of anthelmintic resistance. Both the free-living nematode Caenorhabditis elegans and the ruminant parasite Haemonchus contortus biotransform benzimidazole drugs by glucose conjugation, likely catalysed by UDP-glycosyltransferase (UGT) enzymes. To identify C. elegans genes involved in benzimidazole drug detoxification, we first used a comparative phylogenetic analysis of UGTs from humans, C. elegans and H. contortus, combined with available RNAseq datasets to identify which of the 63 C. elegans ugt genes are most likely to be involved in benzimidazole drug biotransformation. RNA interference knockdown of 15 prioritized C. elegans genes identified those that sensitized animals to the benzimidazole derivative albendazole (ABZ). Genetic mutations subsequently revealed that loss of ugt-9 and ugt-11 had the strongest effects. The "ugt-9 cluster" includes these genes, together with six other closely related ugts. A CRISPR-Cas-9 deletion that removed seven of the eight ugt-9 cluster genes had greater ABZ sensitivity than the single largest-effect mutation. Furthermore, a double mutant of ugt-22 (which is not a member of the ugt-9 cluster) with the ugt-9 cluster deletion further increased ABZ sensitivity. This additivity of mutant phenotypes suggest that ugt genes act in parallel, which could have several, not mutually exclusive, explanations. ugt mutations have different effects with different benzimidazole derivatives, suggesting that enzymes with different specificities could together more efficiently detoxify drugs. Expression patterns of ugt-9, ugt-11 and ugt-22 gfp reporters differ and so likely act in different tissues which may, at least in part, explain their additive effects on drug potency. Overexpression of ugt-9 alone was sufficient to confer partial ABZ resistance, indicating increasing total UGT activity protects animals. In summary, our results suggest that the multiple UGT enzymes have overlapping but not completely redundant functions in benzimidazole drug detoxification and may represent "druggable" targets to improve benzimidazole drug potency.