Going the extra mile: Developing an interactive mobile application for maternal and infant care for tribal birth attendants.

Background: Mobile health applications are an established tool for healthcare management, patient education, and even capacity building for healthcare providers. However, its use among traditional birth attendants (TBAs) is limited. The aim of this study is to explore the needs and bottlenecks of developing an interactive mobile application for maternal and infant care (MAI) of TBAs. Materials and Methods: It is a qualitative study having in-depth interviews (face-to-face approach) conducted among the seekers of MAI services. Setting: This study is conducted in tribal and rural locations in the district Sirohi, Rajasthan. Participants: TBAs and tribal females of reproductive age in tribal-dominated areas have participated. The development of an interactive mobile application MAI has three phases: (1) a need-based approach to identify the needs on the ground; (2) identifying intervention bottlenecks and possible solutions; (3) design and development of the mobile application. Results: Ninety-six tribal females of reproductive age participated in the needs assessment. Eighty percent of them were ≤ 30 years of age and 40% of them were uneducated. Most participants informed that lack of information (culturally/locally appropriate content), peer advocacy, affordability, lack of transportation, and the influence of TBAs are the significant factors for less uptake of maternity and child health services in the tribal and rural areas. Conclusion: The MAI app has culturally/locally appropriate content and is prepared by the local TBAs and Accredited Social Health Activists, with full local character and clothing. MAI app has videos and audio in the local language (Marwari) with pictorial quizzes. Using the MAI app, TBAs may self-educate and guide tribal pregnant women about maternal hygiene and infant healthcare as needed at various stages of pregnancy and childbirth.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

Discovery of low-molecular-weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability.

The HIV capsid (CA) protein is a promising target for anti-AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well-documented CA inhibitor PF74 as our lead compound and designed a series of low-molecular-weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV-2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14-fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV-1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110-fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.

Gum acacia based hydrogels and their composite for waste water treatment: A review.

The non-toxic nature of natural polysaccharides and their biodegradability makes them the first choice of researchers. Various natural polysaccharides are available nowadays, like cellulose, starch, chitosan, gum acacia, guar gum etc. Among these, gum acacia is a common natural polysaccharide presently used in research and technology. It is highly biodegradable, pH stable and shows appropriate water solubility. It is used in research to synthesize hydrogels and hydrogel nanocomposites for various applications because of its antimicrobial, anti-inflammatory and excellent absorption properties. The major fields of applications include the stabilization of metal nanoparticles in the form of nanocomposites, wound dressing materials, delivery systems of various drugs and pharmaceutical agents, bioengineering, tissue engineering, purification of water, synthesis of antibacterial and antifungal composites for agricultural improvements, and many others. Due to the increasing problem of water pollution, the major focus is on research helping to reduce this problem. Gum acacia-based hydrogel and hydrogel composites were synthesized and tested for pollutant removal efficiency from wastewater by different researchers. The research on gum acacia hydrogel and their hydrogel composite applications for water purification, as well as their synthesis processes and properties, are summarized in this review article.

Mapping of adult plant recessive resistance to anthracnose in Indian common bean landrace Baspa/KRC 8.

BACKGROUND: The common bean (Phaseolus vulgaris) has become the food of choice owing to its wealthy nutritional profile, leading to a considerable increase in its cultivation worldwide. However, anthracnose has been a major impediment to production and productivity, as elite bean cultivars are vulnerable to this disease. To overcome barriers in crop production, scientists worldwide are working towards enhancing the genetic diversity of crops. One way to achieve this is by introducing novel genes from related crops, including landraces like KRC 8. This particular landrace, found in the North Western Himalayan region, has shown adult plant resistance against anthracnose and also possesses a recessive resistance gene. METHODS AND RESULTS: In this study, a population of 179 F2:9 RIL individuals (Jawala × KRC 8) was evaluated at both phenotypic and genotypic levels using over 830 diverse molecular markers to map the resistance gene present in KRC 8. We have successfully mapped a resistance gene to chromosome Pv01 using four SSR markers, namely IAC 238, IAC 235, IAC 259, and BM 146. The marker IAC 238 is closely linked to the gene with a distance of 0.29 cM, while the other markers flank the recessive resistance gene at 10.87 cM (IAC 259), 17.80 cM (BM 146), and 25.22 cM (IAC 235). Previously, a single recessive anthracnose resistance gene (co-8) has been reported in the common bean accession AB 136. However, when we performed PCR amplification with our tightly linked marker IAC 238, we got different amplicons in AB 136 and KRC 8. Interestingly, the susceptible cultivar Jawala produced the same amplicon as AB 136. This observation indicated that the recessive gene present in KRC 8 is different from co-8. As the gene is located far away from the Co-1 locus, we suggest naming the recessive gene co-Indb/co-19. Fine mapping of co-Indb in KRC 8 may provide new insights into the cloning and characterization of this recessive gene so that it can be incorporated into future bean improvement programs. Further, the tightly linked marker IAC 238 can be utilized in marker assisted introgression in future bean breeding programs. CONCLUSION: The novel co-Indb gene present in Himalayan landrace KRC 8, showing adult plant resistance against common bean anthracnose, is independent from all the resistance genes previously located on chromosome Pv01.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Incidence, Risk Factors, Characteristics, and Outcome of Chronic Graft Versus Host Disease in Children Undergoing Haploidentical Peripheral Blood Stem Cell Transplant With Post-transplant Cyclophosphamide.

AIM: Chronic graft versus host disease (cGVHD) is a major cause of morbidity postallogeneic peripheral blood stem cell transplant (PBSCT). There is paucity of literature describing incidence, risk factors, characteristics, and outcome of cGVHD in children undergoing haploidentical PBSCT with post-transplant cyclophosphamide (PTCy). Here, we describe our experience from our center regarding the same. METHODS: All children who underwent haploidentical PBSCT with PTCy between January 2016 and December 2021 at our center and survived beyond day+100 post-transplant were included in this retrospective study. Conditioning regimens used were: Thiotepa-Fludarabine-Cyclophosphamide with 2 Gy single fraction total body irradiation, Thiotepa-Busulfan-Fludarabine, Fludarabine-total body irradiation and Fludarabine-Melphalan. Peripheral blood was used as stem cell source in all patients. GVHD prophylaxis was PTCy 50 mg/kg on day +3 and +4, Mycophenolate mofetil and Calcineurin inhibitors. Clinical and laboratory data was electronically retrieved and analyzed based on National Institute of Health Consensus Criteria-2014 at regular intervals. Impact of various patient, donor, and transplant-related factors on development of cGVHD were analyzed. Incidence of relapse, event free survival (EFS) and overall survival (OS) were calculated and compared between cGVHD and no cGVHD groups. Patients with rejection were excluded from risk factor analysis for cGVHD but were considered for survival analysis. RESULTS: Fifty-one children included in this study. Median age of transplant of our cohort was 7.5 years with male:female=1.6:1. Eight patients had rejection with autologous recovery. History of acute GVHD (aGVHD) was present in 15/51 (Grade III to IV in 7/51). cGVHD developed in 19/51 patients (mild-9/51, moderate-6/51, and severe-4/51). Skin was the most common organ involved (100%) followed by gastrointestinal tract (47.4%), liver (36.8%), eyes (21%), lungs (21%), mouth (15.7%), and joints (5.2%). Advanced donor age (>30 y) and previous aGVHD were found to be significantly associated with increased risk of developing cGVHD. At last follow-up, complete response and partial response of cGVHD was seen in 6/19 and 4/19 patients, respectively. Overall mortality was 15/51 (cause of mortality was relapse of cancer 8/15, cGVHD-3/15, other 4/15). EFS and OS of full cohort was 55% and 70.6%, respectively. Compared with patients without cGVHD, patients with cGVHD demonstrated a lower relapse (18.2% vs. 40%, P =0.2333), higher EFS (68.4% vs. 53.1%, P =0.283), and higher OS (73.7% vs. 68.8%, P =0.708). CONCLUSION: Incidence of cGVHD was high in children undergoing haploidentical PBSCT with PTCy. Other than PBSC graft source; donor age and previous aGVHD were the risks factors for development of cGVHD. Patients with cGVHD had lower incidence of relapse translating into better survival but this difference was not statistically significant.

Understanding the Association Between Obesity and Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Introduction Obstructive sleep apnea (OSA) represents a sleep-related impairment linked to upper airway function. The question of whether OSA drives obesity or if shared underlying factors contribute to both conditions remains unresolved. Hence, this present study aims to understand the interplay between obstructive sleep apnea syndrome (OSAS) and obesity through in-depth analysis of anthropometric data within control subjects and OSA patients. Methodology A case-control study was conducted, which included 40 cases and 40 matched healthy controls. Study participants with reported symptoms of snoring, daytime drowsiness, or both were included in the study. All the study participants underwent comprehensive anthropometric assessments such as height, weight, body mass index (BMI), neck circumference, waist circumference, hip circumference, waist-to-hip ratio, skin-fold thickness, and thickness measurements of biceps, triceps, suprailiac, and subscapular muscles. Results Within the OSA group, significant disparities emerged in mean age, waist circumference, waist-to-hip ratio, and diverse fat accumulations encompassing visceral, subcutaneous, trunk, and subcutaneous leg fat. Notably, skin-fold thickness at specific sites - biceps, triceps, subscapula, and suprailiac - demonstrated considerable augmentation relative to the control group. Furthermore, mean values associated with height, weight, BMI, neck circumference, fat percentage, subcutaneous arm fat, entire arm composition, and trunk skeletal muscle either equaled or exceeded those in the control group. However, statistical significance was not attained in these comparisons. Conclusion This investigation underscored a pronounced correlation between numerous endpoints characterizing OSA patients and markers of obesity. Consequently, addressing altered levels of obesity-linked anthropometric variables through pharmacological interventions might hold promise as a pivotal strategy for improving symptoms associated with OSA.

A Survey Study on Knowledge and Attitude Toward the Ethics Committee and Research Ethical Practices Among Researchers From Kuwait.

The integrity of research findings and the safety of participants who voluntarily consent to participate in research studies must be assured through ethical approaches. Additionally, ethical guidelines and the ethics committee protect participants from unfair practices by the research team. Therefore, this study aims to assess the knowledge and attitudes toward the ethics committee and research ethical practices among the researchers of a diabetes institute in Kuwait. An anonymous survey was conducted through an online questionnaire using Microsoft Forms. The study had a response rate of 86%. Among the 55 participants in this study, 43 (78%) had ethics training. Researchers involved in more than four research projects were shown to have a much higher awareness of the ethics committee and its role than researchers involved in no projects. Approximately 90% of researchers had training in research ethics and were knowledgeable about informed consent forms and assent, as well as additional protections for vulnerable populations. Ninety-eight percent of respondents were of the view that an ethics committee was necessary. Our study concluded that most of the researchers at the institute were aware of the role of the ethics committee, and ethical principles. However, we recommend that continuous and customized training on research ethics should be provided.

Exploring internet addiction and its associated factors among college students in Western Rajasthan, India: A mixed-methods study.

Background: With near universal use of internet by college students, there is propensity for internet addiction (IA) among them. This study aimed to estimate the prevalence and predict the factors for internet addiction among college students in Jodhpur, Rajasthan, India, and qualitatively explore the factors associated with internet addiction. Materials and Methods: Explanatory sequential (QUAN-QUAL) mixed-methods design was used. A cross-sectional questionnaire-based survey was conducted among three streams of undergraduate colleges (health, engineering, and others). Survey instruments included Young's internet addiction test (IAT), Pittsburgh Sleep Quality Index (PSQI), and Depression, Anxiety, and Stress Scale-21 (DASS-21) Items. Focus group discussions (FGDs) and in-depth interviews (IDIs) among the students with mild-to-moderate levels of addiction were conducted to understand the reasons for excessive internet use. Results: The prevalence of internet addiction (IA) among the college students was 51% and the rates for mild, moderate, and severe addiction were 31.8%, 18.5%, and 0.7%, respectively. Predictors of IA were male gender, age in years, age of first internet use in years, urban origin, accessing internet at college, mobile internet use, using internet to make online friendship, sleep disturbance, depression, anxiety, and stress. Qualitative study identified five major themes related to situations initiating internet use for nonacademic purpose, content of internet use, triggers for internet overuse/addiction (IA), perceived impact of IA, and measures to overcome IA. Conclusions: Internet addiction was found to be highly prevalent in college students across various streams. Qualitative results provide deeper insights into IA among college students. It is imperative to screen for IA among the students and devise suitable preventive interventions, which can be easily implemented at community level.

Estimating the weight of consumed tobacco product waste in various Indian states: a novel method to assess the potential burden of tobacco product waste.

INTRODUCTION: The direct morbidity and mortality caused by tobacco are well documented, but such products also contribute to a range of environmental pollutants resulting from tobacco product waste. No previous studies have yet quantified tobacco product waste in a low-income and middle-income country (LMIC). This study estimates the potential annual waste generated due to consumption of smoked and smokeless tobacco products in India and its states. METHODOLOGY: We systematically collected samples of smoked and smokeless tobacco products from 33 districts of 17 Indian states/union territories. Stratified weights of plastic, paper, foil and filter packaging components, and gross empty package weights were recorded. Prevalence of smoking and smokeless tobacco use at national and state-level estimates was derived from the Global Adult Tobacco Survey (2016-2017) to quantify waste potentially generated by tobacco products. RESULTS: We included 222 brands of tobacco products (70 cigarette, 94 bidi and 58 smokeless tobacco brands) in the final analysis. A total of 170 331 (±29 332) tonnes of waste was estimated to be generated annually, out of which 43.2% was plastic, 3.6% was foil and 0.8% was filter. Two-thirds of the overall waste was contributed by smokeless products alone. Maximum waste was generated in Uttar Pradesh (20.9%; 35 723.7±6151.6 tonnes), Maharashtra (8.9%; 15 116.84±2603.12 tonnes) and West Bengal (8.6%; 14 636.32±2520.37 tonnes). CONCLUSION: This study provides first of its kind national-level evidence on the types (plastic, paper, foil and filter) and quantity of waste potentially generated by use of tobacco products in India. Similar studies from other LMICs can serve to raise consciousness about many negative environmental impacts of tobacco products and need for policies to address them.

Death, Disability, and Premature Life Years Lost Due to Cigarettes, Bidis, and Smokeless Tobacco in India: A Comparative Assessment.

Background: Due to the staggering number of tobacco users in India, it is important to determine the exact mortality and morbidity rates due to tobacco use. This study aimed to estimate deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) attributable to cigarettes, bidis, and smokeless tobacco (SLT) in India. Methods: Data pooling and meta-analysis were done using case-control studies available on the three types of tobacco products. Health burden was estimated by applying the population attributable fraction (PAF) value to the total disease burden. Findings: A total of 33 studies were included. PAF was calculated for oral and lung cancer as well as ischemic heart disease (IHD) due to cigarettes, oral and lung cancer, IHD, and chronic obstructive pulmonary disease due to bidi, and oral and stomach cancer and IHD due to SLT. Cigarettes resulted in 8.4 million DALYs, 8.26 million YLLs, and 341 deaths; bidis led to 11.7 million DALYs, 10.7 million YLLs, and 478 thousand deaths, and SLTs accounted for 4.38 million DALYs, 4.3 million YLLs, and 171 thousand deaths annually. Conclusion: Evidence of measurable health burden and methodology for calculation for individual states was provided in the study. The generated evidence could be utilized for policy recommendations and revision of the existing taxation norms.

Effects of Sudarshan KriyaYoga and Advanced Meditation Program on Genetic Expression of Pro-inflammatory and Antioxidants Genes.

Background Stress leads to immune system dysregulation and dyshomeostasis at the gene level. Mind-body practices are known to influence genomic expression, leading to better health and quality of life. Objective To assess the effect of Advanced Meditation Program (AMP) on the mRNA expression of pro-inflammatory and antioxidative genes among those already practicing Sudarshan Kriya Yoga (SKY). Methods A total of 97 healthy volunteers participated in the study, distributed into two groups. The Group I SKY practitioners attended a four-day AMP (50 participants with an average age of 38.8 ± 11.9 consisting of 37 females and 13 males); they are first-time participants of the AMP. Group II SKY practitioners, on the other hand, consisted of 47 participants with an average age of 36.4 ± 9.3 with 43 females and four males. At day 0, day 5, and day 90, the mRNA expression of pro-inflammatory genes, namely interleukin (IL) 1ß, IL6, and the tumor necrosis factor (TNF), and the expression of antioxidative genes, namely superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) was observed. The data were analysed in two phases due to the emergence of coronavirus disease 2019 (COVID-19): (i) pre-COVID-19 and (ii) during COVID-19. Results In the pre-COVID-19 data set, IL1ß, IL6, and TNF were found to have decreased in both groups. There is a significant increase in the expression of SOD and catalase in Group I and a decrease in Group II by day 90. During COVID-19, pro-inflammatory genes increased in Group I and had no significant change in Group II. All three antioxidant genes had decreased expression by day 90 in Group I; SOD decreased in Group II. Interpretation and conclusions Reduced expression of pro-inflammatory genes and increase in the expression of antioxidative genes during the pre-COVID-19 time suggest that the practice of SKY and added AMP may enhance antioxidative defense and may reduce the chance of getting diseases related to inflammation in the body.

Is maternal anemia among tribal women being neglected? A study from Southern Rajasthan.

Poor birth outcomes have been linked to maternal anemia. Tribal women are at higher risk of malnutrition and disease due to sociocultural barriers and poor educational status. The data on the prevalence of maternal anemia and its associated factors among pregnant tribal women are limited. A community-based cross-sectional study was conducted among 429 pregnant tribal women for maternal anemia from August 2021 to June 2022. A structured questionnaire was employed to collect sociodemographic data. The prevalence of anemia was 85.7%, with a mean hemoglobin level of 9.21 ± 1.3 g/dL. On applying WHO 2011 anemia criteria for pregnant women, 25.0% had mild anemia, 73.4% had moderate anemia, and 1.6% had severe anemia. The significant factors associated with anemic condition were household condition, monthly income, and husband's occupation. The higher prevalence of anemia among pregnant tribal women is alarming that necessitates a rethinking of health infrastructure and outreach in tribal dominant areas.

Effect of prey density on the performance of Eupeodes corollae and its predation rate against the cabbage aphid, Brevicorynae brassicae (L.).

Eupeodes corollae (F.) (Diptera: Syrphidae) is the most abundant syrphid fly which is distributed worldwide and is the sole predator of aphids. Therefore, the present study was conducted to evaluate the predation rate and functional response of E. corollae against the cabbage aphid, Brevicoryne brassicae (L.). The experiment was carried out under laboratory conditions at 25 ± 2°C with 60-70% relative humidity. The results revealed that age-specific net predation rate (qx) increased after the 4th day and a peak was recorded on the 10th day of pivotal age in the third larval instar. The stable host kill rate and finite host kill rate of E. corollae were 18.63 and 21.07, respectively, against the B. brassicae and predicted that a mean of 20.78 aphids was needed for E. corollae to produce one offspring. A negative linear coefficient (P < 0) indicated the type II functional response for all larval instars of E. corollae against the B. brassicae. At higher prey density, the prey consumption was significantly at par with second and third instar larvae of E. corollae as the prey consumption was increased with increasing the prey density, which then decreased after attaining the upper asymptote (76.40 and 81.40% consumption, respectively). The Roger's predator random equation for type II functional response was fitted to estimate attack rate (a) and handling time (Th). The maximum prey consumption was recorded for third instar of E. corollae with a higher attack rate (0.336 h-1) and lower handling time (0.514 h) against B. brassicae, followed by the second and first instar. Thus, it is concluded that the third larval instar of E. corollae was the voracious feeder and used as an efficient biocontrol agent in the IPM programme.

Valorization of Seawater Reverse Osmosis Brine by Monovalent Ion-Selective Membranes through Electrodialysis.

This paper proposes the use of monovalent selective electrodialysis technology to concentrate the valuable sodium chloride (NaCl) component present in seawater reverse osmosis (SWRO) brine for direct utilization in the chlor-alkali industry. To enhance monovalent selectivity, a polyamide selective layer was fabricated on commercial ion exchange membranes (IEMs) through interfacial polymerization (IP) of piperazine (PIP) and 1,3,5-Benzenetricarbonyl chloride (TMC). The IP-modified IEMs were characterized using various techniques to investigate changes in chemical structure, morphology, and surface charge. Ion chromatography (IC) analysis showed that the divalent rejection rate was more than 90% for IP-modified IEMs, compared to less than 65% for commercial IEMs. Electrodialysis results demonstrated that the SWRO brine was successfully concentrated to 14.9 g/L NaCl at a power consumption rate of 3.041 kWh/kg, indicating the advantageous performance of the IP-modified IEMs. Overall, the proposed monovalent selective electrodialysis technology using IP-modified IEMs has the potential to provide a sustainable solution for the direct utilization of NaCl in the chlor-alkali industry.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

Escaping from Flatland: Multiparameter Optimization Leads to the Discovery of Novel Tetrahydropyrido[4,3-d]pyrimidine Derivatives as Human Immunodeficiency Virus-1 Non-nucleoside Reverse Transcriptase Inhibitors with Superior Antiviral Activities against Non-nucleoside Reverse Transcriptase Inhibitor-Resistant Variants and Favorable Drug-like Profiles.

In the current landscape of antiretroviral options, there remains an urgent need for novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved resistance profiles and safety properties. Herein, a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives were discovered utilizing the "escape from flatland" strategy. The most potent inhibitor 10c was endowed with broad-spectrum antiviral activity and improved resistance profiles against NNRTI-resistant variants compared to efavirenz and etravirine. Molecular simulations were investigated to furnish insights into the biological results. Drug-likeness assessment showed that 10c exhibited desirable physicochemical properties and in vitro metabolic stability. Notably, lower cytochrome P450 inhibition and human ether-à-go-go-related gene blockade liability were observed for 10c than those for etravirine and rilpivirine. Besides, 10c was characterized by excellent in vivo safety properties without acute/subacute toxicity and organ pathological damage. Overall, our multiparameter optimization campaign led to the identification of 10c with excellent antiviral activities and favorable drug-like profiles that could serve as an ideal drug candidate for further development.

Application of Indian Diabetic Risk Score (IDRS) and Community Based Assessment Checklist (CBAC) as Metabolic Syndrome prediction tools.

BACKGROUND: Indian Diabetic Risk Score (IDRS) and Community Based Assessment Checklist (CBAC) are easy, inexpensive, and non-invasive tools that can be used to screen people for Metabolic Syndrome (Met S). The study aimed to explore the prediction abilities of IDRS and CBAC tools for Met S. METHODS: All the people of age ≥30 years attending the selected rural health centers were screened for Met S. We used the International Diabetes Federation (IDF) criteria to diagnose the Met S. ROC curves were plotted by taking Met S as dependent variables, and IDRS and CBAC scores as independent/prediction variables. Sensitivity (SN), specificity (SP), Positive and Negative Predictive Value (PPV and NPV), Likelihood Ratio for positive and negative tests (LR+ and LR-), Accuracy, and Youden's index were calculated for different IDRS and CBAC scores cut-offs. Data were analyzed using SPSS v.23 and MedCalc v.20.111. RESULTS: A total of 942 participants underwent the screening process. Out of them, 59 (6.4%, 95% CI: 4.90-8.12) were found to have Met S. Area Under the Curve (AUC) for IDRS in predicting Met S was 0.73 (95%CI: 0.67-0.79), with 76.3% (64.0%-85.3%) sensitivity and 54.6% (51.2%-57.8%) specificity at the cut-off of ≥60. For the CBAC score, AUC was 0.73 (95%CI: 0.66-0.79), with 84.7% (73.5%-91.7%) sensitivity and 48.8% (45.5%-52.1%) specificity at the cut-off of ≥4 (Youden's Index, 2.1). The AUCs of both parameters (IDRS and CBAC scores) were statistically significant. There was no significant difference (p = 0.833) in the AUCs of IDRS and CBAC [Difference between AUC = 0.00571]. CONCLUSION: The current study provides scientific evidence that both IDRS and CBAC have almost 73% prediction ability for Met S. Though CBAC holds relatively greater sensitivity (84.7%) than IDRS (76.3%), the difference in prediction abilities is not statistically significant. The prediction abilities of IDRS and CBAC found in this study are inadequate to qualify as Met S screening tools.