Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India.

INTRODUCTION: There are around 250 million adolescents (10-19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation. METHODS: Case study method will be used and the data will include a mix of quantitative metrics and qualitative data. The UK Medical Research Council's guidance on evaluating complex interventions, the Reach, Efficacy, Adoption, Implementation and Maintenance Framework and the Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Safety/Side Effects and, Equity criteria will be used to develop a conceptual framework and a priori codes for qualitative data analysis. Quantitative data will be analysed using descriptive statistics. Implementation fidelity will also be measured. DISCUSSION: The process evaluation will provide an understanding of outcomes and causal mechanisms that influenced any change in trial outcomes. ETHICS AND DISSEMINATION: Ethics Committee of the George Institute for Global Health India (project number 17/2020) and the Research Governance and Integrity Team, Imperial College, London (ICREC reference number: 22IC7718) have provided ethics approval. The Health Ministry's Screening Committee has approved to the study (ID 2020-9770). TRIAL REGISTRATION NUMBER: CTRI/2022/02/040307.

Umbilical Endometriosis in a Surgically Naïve Multiparous Young Female.

The existence of functional endometrial tissue outside the uterus is known as endometriosis. It is a benign estrogen-dependent gynecological condition that affects 5%-10% of women who are of reproductive age. Endometriosis often affects the ovary and fallopian tubes, although it can also occur in nonpelvic areas. The most typical location for extra-pelvic endometriosis is the abdomen. Umbilical endometriosis is a rare condition accounting for 0.5%-1.0% of all cases of endometriosis. In 3% of cases, there is a chance of malignant change. This disorder's precise etiology is uncertain. Recurrent discomfort and swelling around the umbilicus are the classic manifestations. In this instance, we describe a patient with primary umbilical endometriosis (PUE) who had cyclical bleeding and swelling over the umbilicus and was surgically naive. This case will demonstrate how, particularly in surgically naïve instances, diagnosis of PUE is frequently delayed due to ignorance of the entity.

QTLs and Genes for Salt Stress Tolerance: A Journey from Seed to Seed Continued.

Rice (Oryza sativa L.) is a crucial crop contributing to global food security; however, its production is susceptible to salinity, a significant abiotic stressor that negatively impacts plant germination, vigour, and yield, degrading crop production. Due to the presence of exchangeable sodium ions (Na+), the affected plants sustain two-way damage resulting in initial osmotic stress and subsequent ion toxicity in the plants, which alters the cell's ionic homeostasis and physiological status. To adapt to salt stress, plants sense and transfer osmotic and ionic signals into their respective cells, which results in alterations of their cellular properties. No specific Na+ sensor or receptor has been identified in plants for salt stress other than the SOS pathway. Increasing productivity under salt-affected soils necessitates conventional breeding supplemented with biotechnological interventions. However, knowledge of the genetic basis of salinity stress tolerance in the breeding pool is somewhat limited because of the complicated architecture of salinity stress tolerance, which needs to be expanded to create salt-tolerant variants with better adaptability. A comprehensive study that emphasizes the QTLs, genes and governing mechanisms for salt stress tolerance is discussed in the present study for future research in crop improvement.

Health and demographic indicators of selected districts of India: An impact of Swasthya Rakshan Programme (SRP).

Swasthya Rakshan Programme (SRP) provides health care services through Ayurveda, an initiative of the Government of India that aims to survey and create alertness of essential health appliances to ameliorate society from its grassroots level. The present study aimed to survey the prevailing health standards of residents in certain districts of India and to record the prevalence of diseases among them according to their living conditions, food habits, lifestyle, education, occupation and other socio-economic status. Data was collected through a community-based cross-sectional survey conducted from April 2018 to March 2019 in 22 Districts of 19 states in India. A stratified multi-stage sampling design was adopted for the survey. Documentation of demographic profile, food habits, lifestyle, hygiene status, and existing health conditions was assessed. A pre-designed semi-structured questionnaire was used for the collection of the data. Before initiating the programme, written consent was obtained. In this study, from 162 selected villages/colonies/areas, a total of 562,913 population and 81,651 households were surveyed. Sixty-nine thousand three hundred nineteen patients were cared for various ailments through health camps. The study found that the most prevalent disease in the concerned population was 'Sandhivata' (Osteo-arthritis), that is, 43.0%, followed by 'Dourbalya' (Debility), that is, 11.7%. The study includes insightful analyses of comprehensive demographic and health indicators classified by various socio-economic categories. The collected data regarding the prevalence of diseases with their sociodemographic correlations may provide a better understanding of the locality and thus may help in all future health endeavours.

Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment.

Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal (n = 10) or impaired (n = 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration-time curve from time 0 to infinity (AUCinf) and maximum concentration (Cmax)] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUCinf and Cmax were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe and well tolerated in both studies. These results support the use of approved lenacapavir dosing regimen in patients with mild (CPT Class A: score 5-6) or moderate hepatic impairment as well as in patients with mild (60 ≤ CLcr ≤ 89 mL/min), moderate (30 ≤ CLcr ≤ 59 mL/min), and severe renal impairment.

Xanthogranulomatous Salpingo-Oophoritis as a Rare Presentation in Pelvic Inflammatory Disease.

Xanthogranulomatous salpingo-oophoritis is an infrequent and challenging inflammatory condition of the female genital tract. It involves the destruction of the fallopian tube and ovarian tissue by infiltrating inflammatory cells comprising lipid-laden macrophages, lymphocytes, plasma cells, and multinucleated giant cells. While more commonly found in other organs like the gallbladder and kidney, its occurrence in the female genital tract is rare. We present a case of xanthogranulomatous salpingo-oophoritis in a 45-year-old woman, shedding light on its diagnostic and clinical complexities. Notably, this case features a rare histopathological finding of coexisting salpingitis isthmic nodosa (SIN) with xanthogranulomatous inflammation, adding to its uniqueness.

Pharmacokinetics, Disposition, and Biotransformation of [14C]Lenacapavir, a Novel, First-in-Class, Selective Inhibitor of HIV-1 Capsid Function, in Healthy Participants Following a Single Intravenous Infusion.

BACKGROUND AND OBJECTIVE: Lenacapavir (LEN) is a novel, first-in-class, multistage, selective inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function recently approved for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. The purpose of this multicohort study was to evaluate the pharmacokinetics, metabolism, excretion, safety, and tolerability of LEN following a single intravenous (IV) infusion of 10 mg LEN or 20 mg [14C]LEN in healthy participants. METHODS: Twenty-one healthy adult participants were enrolled into the study and received either a single IV dose of 10 mg LEN (n = 8 active, n = 3 placebo; cohort 1) or a single IV dose of 20 mg [14C]LEN containing 200 µCi (n = 10; cohort 2). Blood, urine, and feces samples (when applicable) were collected after dosing, and radioactivity (cohort 2) was assessed using liquid scintillation counting in both plasma and excreta. LEN in plasma was quantified by liquid chromatography (LC) tandem mass spectroscopy (MS/MS) method bioanalysis. Metabolite profiling in plasma and excreta were performed using LC-fraction collect (FC)-high-resolution MS and LC-FC-accelerator mass spectrometry in plasma. RESULTS: Between the 10 mg and 20 mg doses of LEN, the observed plasma exposure of LEN doubled, while the elimination half-life was similar. Following administration of 20 mg [14C]LEN (200 µCi), the mean cumulative recovery of [14C] radioactivity was 75.9% and 0.24% from feces and urine, respectively. The mean whole [14C] blood-to-plasma concentration ratio was 0.5-0.7, which showed a low distribution of LEN to red blood cells. Intact LEN was the predominant circulating species in plasma (representing 68.8% of circulating radioactivity), and no single metabolite contributed to > 10% of total radioactivity exposure through 1176 h postdose. Similarly, intact LEN was the most abundant component (32.9% of administered dose; 75.9% of recovered dose) measured in feces, with metabolites accounting for trace amounts. These results suggest metabolism of LEN is not a primary pathway of elimination. Of the metabolites observed in the feces, the three most abundant metabolites were direct phase 2 conjugates (glucuronide, hexose, and pentose conjugates), with additional metabolites formed to a lesser extent via other pathways. The administered LEN IV doses were generally safe and well-tolerated across participants in this study. CONCLUSIONS: The results of this mass balance study indicated that LEN was majorly eliminated as intact LEN via the feces. The renal pathway played a minor role in LEN elimination (0.24%). In addition, no major circulating metabolites in plasma or feces were found, indicating minimal metabolism of LEN.

Using formative research to inform a mental health intervention for adolescents living in Indian slums: the ARTEMIS study.

BACKGROUND: Adolescents are vulnerable to stressors because of the rapid physical and mental changes that they go through during this life period. Young people residing in slum communities experience additional stressors due to living conditions, financial stress, and limited access to healthcare and social support services. The Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) study, is testing an intervention intended to improve mental health outcomes for adolescents living in urban slums in India combining an anti-stigma campaign with a digital health intervention to identify and manage depression, self-harm/suicide risk or other significant emotional complaints. METHODS: In the formative phase, we developed tools and processes for the ARTEMIS intervention. The two intervention components (anti-stigma and digital health) were implemented in purposively selected slums from the two study sites of New Delhi and Vijayawada. A mixed methods formative evaluation was undertaken to improve the understanding of site-specific context, assess feasibility and acceptability of the two components and identify required improvements to be made in the intervention. In-depth interviews and focus groups with key stakeholders (adolescents, parents, community health workers, doctors, and peer leaders), along with quantitative data from the digital health platform, were analysed. RESULTS: The anti-stigma campaign methods and materials were found to be acceptable and received overall positive feedback from adolescents. A total of 2752 adolescents were screened using the PHQ9 embedded into a digital application, 133 (4.8%) of whom were identified as at high-risk of depression and/or suicide. 57% (n = 75) of those at high risk were diagnosed and treated by primary health care (PHC) doctors, who were guided by an electronic decision support tool based on WHO's mhGAP algorithm, built into the digital health application. CONCLUSION: The formative evaluation of the intervention strategy led to enhanced understanding of the context, acceptability, and feasibility of the intervention. Feedback from stakeholders helped to identify key areas for improvement in the intervention; strategies to improve implementation included engaging with parents, organising health camps in the sites and formation of peer groups. TRIAL REGISTRATION: The trial has been registered in the Clinical Trial Registry India, which is included in the WHO list of Registries, Reference number: CTRI/2022/02/040307. Registered 18 February 2022.

Lenacapavir: A Novel, Potent, and Selective First-in-Class Inhibitor of HIV-1 Capsid Function Exhibits Optimal Pharmacokinetic Properties for a Long-Acting Injectable Antiretroviral Agent.

Lenacapavir (LEN) is a picomolar first-in-class capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) with a multistage mechanism of action and no known cross resistance to other existing antiretroviral (ARV) drug classes. LEN exhibits a low aqueous solubility and exceptionally low systemic clearance following intravenous (IV) administration in nonclinical species and humans. LEN formulated in an aqueous suspension or a PEG/water solution formulation showed sustained plasma exposure levels with no unintended rapid drug release following subcutaneous (SC) administration to rats and dogs. A high total fraction dose release was observed with both formulations. The long-acting pharmacokinetics (PK) were recapitulated in humans following SC administration of both formulations. The SC PK profiles displayed two-phase absorption kinetics in both animals and humans with an initial fast-release absorption phase, followed by a slow-release absorption phase. Noncompartmental and compartmental analyses informed the LEN systemic input rate from the SC depot and exit rate from the body. Modeling-enabled deconvolution of the input rates from two processes: absorption of the soluble fraction (minor) from a direct fast-release process leading to the early PK phase and absorption of the precipitated fraction (major) from an indirect slow-release process leading to the later PK phase. LEN SC PK showed flip-flop kinetics due to the input rate being substantially slower than the systemic exit rate. LEN input rates via the slow-release process in humans were slower than those in both rats and dogs. Overall, the combination of high potency, exceptional stability, and optimal release rate from the injection depot make LEN well suited for a parenteral long-acting formulation that can be administered once up to every 6 months in humans for the prevention and treatment of HIV-1.

Role of Mutant Phosphate Solubilizing Microorganism on Growth of Brassica juncea (L.) cv RH 30.

Phosphorus is the second major plant nutrient and the availability of this element to plants is a major challenge due to conversion to insoluble form by chemical reactions with metal cations depending upon the soil pH. Total of sixty eight isolates of phosphate solubilizing bacteria from rhizosphere of mustard grown in different region of Haryana was studied. The isolates were mutagenised by giving treatment of Nitrosoguanidine (50 ug/ml). Three PSB strains (15M, 22M and 25M) and six mutants (15M2, 15M6, 22M28, 22M29, 25M11 and 25M30) were evaluated for their establishment in the rhizosphere, their effect on biomass production in mustard (Brassica juncea). Total bacterial count in rhizosphere increased after 30 and 40 days of sowing while decrease in growth was observed at 60 days of sowing. The phosphate solubilizing bacterial count in the rhizosphere varied from 1 to 24, 2 to 20 and 1 to 11 at 30, 45 and 60 days after sowing. Phosphate uptake also increased upto 11-21% which shows thatmutants had significant effect on increase in plant dry biomass and P-uptake under pot house conditions.

Trends and advances in pre- and post-harvest processing of linseed oil for quality food and health products.

Linseed is an ancient crop used for diverse purposes since the beginning of civilization. In recent times, linseed has emerged as a superfood due to its high content of health-promoting omega-3 fatty acids and other bioactive compounds. Among primary health effects, it has potential to manage hypertension, diabetes, osteoporosis, atherosclerosis, cancer, arthritis, neurological, cardiovascular diseases including blood cholesterol levels, constipation, diarrhea, and autoimmune disorders etc. due to the presence of omega-3 fatty acid, lignans, high dietary fibers, and proteins, whereas, secondary health effects comprise of relieving from various skin disorders. Due to these health-beneficial properties, interest in linseed oil necessitates the intensification of research efforts on various aspects. These include cultivation technology, varietal and genetic improvement, post-harvest processing, profiling of nutrients and bioactive compounds, pre-clinical and clinical studies, etc. The present review discussed the advances in linseed research including pre- and post-harvest processing. However, focus on the bioactive compounds present in linseed oil and their health effects are also presented. Linseed cultivation, pre- and post-harvest processing aspects are covered including climatic, edaphic, agronomic factors, type of cultivar and storage conditions etc, which impact the overall oil yield and its nutritional quality. Various emerging applications of linseed oil in functional food, nutraceutical, pharmaceutical, and cosmeceutical preparations were also presented in detail. Further, recommendations were made on linseed oil research in the field of genetics, breeding germplasm resources and genome editing for exploring its full applications as a nutrition and health product.

Production, Characterization and Prebiotic Potential of Xylooligosaccharides Produced from Wheat Bran using Enterobacter hormaechei KS1 Xylanase.

In the present investigation, xylooligosaccharides were produced from wheat bran and wheat bran extracted xylan through enzymatic hydrolysis using xylanase from novel Enterobacter hormaechei KS1. Xylooligosaccharides/reducing sugars production from wheat bran was found maximum (374 mg/g) when 4.0% of wheat bran was treated with 375 units (IU/mL) of Enterobacter hormaechei KS1 xylanase at pH 6.0 and incubated at 50 °C for 24 h of incubation. In case of wheat bran extracted xylan 419 mg/g of xylooligosaccharides were produced when 3% of extracted xylan was incubate for 8 h. Analysis of the enzymatic hydrolysate through high performance liquid chromatography equipped with refractive index detector showed the presence of xylose, xylopentose and xylohexose. The decrease in pH with 1.0% dose of xylooligosacchaides produced from extracted xylan hydrolysis using E. hormaechei KS1 xylanase showed more decrease with L. rhamnosus (6.72 to 5.94) followed by L. brevis (6.71 to 6.15) and L. plantarum (6.71 to 6.41). In case of increase in optical density both wheat bran and wheat bran extracted xylan generated xylooligosaccharides exhibited similar pattern i.e., L. rhamnosus > L. plantarum > L. brevis.

Influence of Windowing and Evaluation of Metal Artifact Reduction Algorithm on Five Different Restorative Materials by Using Different Cone Beam Computed Tomography (CBCT) Scanners: A CBCT Study.

OBJECTIVES: To assess the influence of windowing, and to evaluate, and compare the effect of the metal artifact reduction (MAR) and non-metal artifact reduction (non-MAR) algorithms on different high-density restorative dental materials using different cone beam computed tomography (CBCT) devices. MATERIAL AND METHOD: Height and diameter of all cylindrical shape metals including amalgam, cobalt-chromium, composite, gutta-percha, and titanium were measured using a digital caliper device. Polymethylmethacrylate block and arch phantom with a cylindrical-shaped perforation containing five different metals were submitted to tomographic acquisition with six different cone beam computed tomographic devices in small fields of view with their MAR enabled and disabled. Windowing was done using ITK-SNAP software (3.8.2) which was used as a contrast medial tool for window level and window width. The data was analyzed for probability distribution using the Kolmogorov-Smirnov test, where a p-value of <0.05 indicated that the data were not normally distributed. The comparison of length and width was done using the Wilcoxon sign rank test. Comparison of categorical variables was done using the Chi-square test where a p-value of <0.05 was considered statistically significant. RESULTS: Length and width of all these metals measured using MAR and non-MAR CBCT were found to be statistically non-significant (p-value of >0.05). MAR algorithm significantly reduces metals artifact produced by high-density restorative materials (p-value of <0.05). CONCLUSION: Amalgam and cobalt-chromium produced more artifacts while composite and gutta-percha did not produce enough artifacts to be reduced by the MAR algorithm. Large window width and high window level would be beneficial to reduce the metal artifact.

Genetic and epigenetic alterations in MGMT gene and correlation with concomitant chemoradiotherapy (CRT) in cervical cancer.

PURPOSE: The MGMT (O6-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer. METHODS: A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0. RESULTS: Individuals with GG genotype, G allele of rs2308327, and haplotype 'TA' of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25 months significant in comparison to methylated MGMT promoter. CONCLUSION: Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.

Single Nucleotide Polymorphisms in Cytokine Genes are Associated with the Susceptibility to Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of cancer among men in the Indian subcontinent. Cytokines regulate inflammation and angiogenesis in a variety of cancers. Genetic variability in the cytokine genes can potentially influence the predisposition to oral carcinogenesis. The aim of the current study was to investigate the associations of SNPs in cytokine genes with the susceptibility of oral squamous cell carcinoma. In the present study, we have analyzed the allelic frequency of 32 single nucleotide polymorphisms (SNPs) using MassArray-based iPLEX assay in 16 cytokine genes in 166 OSCC patients and 151 healthy subjects from central India. Out of 32 SNPs analyzed, five SNPs were significantly associated with the risk of OSCC. AA and GG genotypes of IL-1ß +3953 were associated with an increased and decreased risk of OSCC, respectively. In several genetic models, GG genotype and G allele in IL-12A 3'UTR G>A were found to be associated with an increased risk of OSCC. Similarly, the GG genotype of IL-12B +1188 T>G was associated with increased susceptibility to OSCC. We conclude that SNPs in the genes coding for IL-1ß, IL-12A and IL-12B are associated with increased genetic susceptibility to OSCC in the central Indian population.

A prospective randomized comparative study to evaluate the effect of palliative hypo-fractionated radiotherapy with concurrent chemotherapy versus hypo-fractionated radiotherapy alone in advanced and unresectable head and neck cancer with no metastasis.

Introduction: A short duration, palliative radiotherapy schedule for locally advanced and unresectable head and neck cancer (LAUHNC) was evaluated in terms of palliation of cancer-related symptoms and acute toxicities. Aims and objectives: The aim of the study was to compare the role and feasibility of hypo-fractionated radiotherapy with concurrent chemotherapy and hypo-fractionated radiotherapy in LAUHNC. Materials and methods: All the patients included in this study of LAUHNC were not fit for curative treatment. These patients are assessed on the basis of quality of life (QOL), tumour response, toxicities, and relief in symptoms. QOL was assessed on the basis of University of Washington QOL questionnaire version 4 before and after treatment. Patients are divided into two arms, Arm A patients received 40 Gy in ten fractions concurrent cisplatin 50 mg/m2 with weekly and Arm B patients received 40 Gy in ten fractions. To assess the tumour response response evaluation criteria in solid tumours criteria were used. Results: A total of 40 patients were enrolled in this study, with 20 patents in both arms. Three patients defaulted during treatment and one patient died during treatment. A total of 36 patients completed treatment. Before treatment common complaints was distressing pain in primary site, and difficulty in chewing and swallowing. After treatment there was reduction of pain and improvement in swallowing in both arms. Overall QOL improvement in Arm A (28.89 ± 18.44 to 46.67 ± 15.34) and in Arm B (31.11 ± 15.68 to 43.33 ± 15.72). Neither of the arms experienced grade IV mucositis and skin reaction. Conclusion: Toxicity in the form of mucositis and dermatitis was higher in the concurrent hypo-fractioned arm compared to the only hypo-fractionated radiotherapy arm during the treatment and in follow up period. The QOL in both individual arms showed statistically significant results, however when the QOL of both the arms was compared, the results were not statistically significant.

Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

OBJECTIVE: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders. METHODS: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA. Regulatory, academic, and industry stakeholders, as well as patient representatives, participated in the workshop, which consisted of 4 sessions, including panel discussions. RESULTS: The workshop facilitated broad public discussion of challenges facing the development of pJIA therapeutics, highlighting areas of need and outlining opportunities to expedite development, while underscoring the necessity of close collaboration between all stakeholders, including patients and families. CONCLUSION: This report summarizes key aspects of the workshop, including the appropriate application of innovative approaches to the development of pJIA therapeutics, including extrapolation, to address current challenges and provide timely access to newer safe and effective treatments. Long-term safety assessment is of pressing concern to stakeholders and cannot be fully extrapolated from adult studies but requires consistent postmarketing long-term follow-up.

Priming COVID-19's consequences can increase support for investments in public health.

Can messaging that emphasizes the costs of COVID-19 increase popular support for more proactive public health policies? People who experience disasters often become more supportive of policies to address their underlying causes, and the pandemic may have similar spillover effects for public opinion. To test this idea, the study implements a survey experiment in Italy, Germany, and the United States in which half of the respondents were randomly assigned to a prime about the impact of the pandemic prior to answering questions about their support for public health policies. The results show that respondents who received the prime became more favorable toward increased government spending on domestic and foreign public health programs alike. These treatment effects were consistent across countries, across two different surveys in the United States conducted at different points in time, and across partisan subgroups. However, the treatment did not consistently increase support for more active and intrusive government policies to address specific public health challenges like smoking or HIV/AIDS. The results suggest that public health advocates may benefit from messaging that connects COVID-19 to the need for public health funding beyond the context of the pandemic.

Reducing options of ammonia volatilization and improving nitrogen use efficiency via organic and inorganic amendments in wheat (Triticum aestivum L.).

Background: This study investigates the effect of organic and inorganic supplements on the reduction of ammonia (NH3) volatilization, improvement in nitrogen use efficiency (NUE), and wheat yield. Methods: A field experiment was conducted following a randomized block design with 10 treatments i.e., T1-without nitrogen (control), T2-recommended dose of nitrogen (RDN), T3-(N-(n-butyl) thiophosphoric triamide) (NBPT @ 0.5% w/w of RDN), T4-hydroquinone (HQ @ 0.3% w/w of RDN), T5-calcium carbide (CaC2 @ 1% w/w of RDN), T6-vesicular arbuscular mycorrhiza (VAM @ 10 kg ha-1), T7-(azotobacter @ 50 g kg-1 seeds), T8-(garlic powder @ 0.8% w/w of RDN), T9-(linseed oil @ 0.06% w/w of RDN), T10-(pongamia oil @ 0.06% w/w of RDN). Results: The highest NH3 volatilization losses were observed in T2 at about 20.4 kg ha-1 per season. Significant reduction in NH3 volatilization losses were observed in T3 by 40%, T4 by 27%, and T8 by 17% when compared to the control treatment. Soil urease activity was found to be decreased in plots receiving amendments, T3, T4, and T5. The highest grain yield was observed in the T7 treated plot with 5.09 t ha-1, and straw yield of 9.44 t ha-1 in T4. Conclusion: The shifting towards organic amendments is a feasible option to reduce NH3 volatilization from wheat cultivation and improves NUE.