Deucravacitinib: moderate-to-severe plaque psoriasis preventable?

Psoriasis is a persistent, inflammatory, and autoimmune condition that is difficult to treat. Estimates of the prevalence of psoriasis in people range from 0.27 % (95 % confidence interval 0.17 to 0.36) to 11.4 %, depending on factors such as age, sex, geography, ethnicity, genetics, and environmental factors. While systemic treatments are typically required for patients with moderate-to-severe instances of psoriasis, topical therapies are frequently effective for treating minor forms. In fact, phototherapy is frequently constrained by logistical considerations, and conventional systemic therapies are frequently avoided due to contraindications or the danger of adverse outcomes. In order to better serve the patient and achieve a greater level of quality of life, especially in order to sustain long-term efficacy, there is still a need for innovative therapies, which are always welcomed. Deucravacitinib is a first-in-class oral tyrosine kinase 2 (TYK2) inhibitor that is extremely selective. Through an allosteric mechanism, it stabilises an inhibitory connection between the regulatory and catalytic domains of TYK2's pseudokinase regulatory domain, which is catalytically inactive. This can be used to treat a variety of immune-mediated conditions, such as inflammatory bowel disease, lupus, psoriatic arthritis, and psoriasis. US-FDA has approved this drug on 9 September 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article aims to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis.

Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).

Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.

Safety monitoring of precautionary third dose of COVID-19 vaccines in a district in Northern India.

Background: The World Health Organization (WHO) declared Coronavirus disease-19 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) a pandemic on March 11, 2020. On 16th January 2021, India began its vaccination programme using two COVID-19 vaccines (Covishield and Covaxin). Precautionary dose (booster shots) was administered to health and front-line workers in the beginning and then to all eligible populations. Material and Methods: This was a descriptive observational study conducted in the COVID-19 vaccination centres of Karnal district and the ADR monitoring centre, KCGMC, Karnal. During the visits to vaccination centres, all beneficiaries of the precautionary third dose of COVID-19 vaccines as well as healthcare workers were sensitized to report in case of any adverse event following vaccination as part of the policy of the vaccination programme run by the government and Pharmacovigilance Programme of India. The data were collected in suspected adverse drug reaction (ADR) reporting form version 1.4, and causality assessment was done as per the WHO-UMC scale. The data were analysed as simple proportions and percentages. Results: The booster dose was administered to 72,853 individuals, while the 1st dose and 2nd dose were given to 13,30,042 and 10,73,050, respectively. Only three ADRs were reported with the booster dose in 34 vaccination centres in the Karnal district. These three ADRs were classified as unlikely on causality assessment and hence not included in the analysis. Conclusion: The booster dose administered for the prevention of COVID-19 has been found to be reasonably safe. The population who received COVID-19 booster doses was significantly less than the populations who received the first and second doses, which suggests a low acceptance rate.

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission.

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Current Trends and Outcomes in Cellular Therapy Activity in the United States, Including Prospective Patient-Reported Outcomes Data Collection in the Center for International Blood and Marrow Transplant Research Registry.

The Center for International Blood and Marrow Transplant Research (CIBMTR) prepares an annual set of summary slides to summarize the trends in transplantation and cellular therapies. For the first time in the 2023 summary slides, the CIBMTR incorporated data for patients receiving chimeric antigen receptor T cell (CAR-T) infusions. In addition, data on patient-reported outcomes (PROs) are included. This report aims to update the annual trends in US hematopoietic cell transplantation (HCT) activity and incorporate data on the use of CAR-T therapies. A second aim is to present and describe the development, implementation, and current status of PRO data collection. In August 2020, the CIBMTR launched the Protocol for Collection of Patient-Reported Outcomes Data (CIBMTR PRO Protocol). The CIBMTR PRO Protocol operates under a centralized infrastructure to reduce the burden to centers. Specifically, PRO data are collected from a prospective convenience sample of adult HCT and CAR-T recipients who received treatment at contributing centers and consented for research. Data are merged and stored with the clinical data and used under the governance of the CIBMTR Research Database Protocol. Participants answer a series of surveys developed by the Patient Reported Outcomes Measurement Information System (PROMIS) focusing on physical, social and emotional, and other measures assessing financial well-being, occupational functioning, and social determinants of health. To complement traditionally measured clinical outcomes, the surveys are administered at the same time points at which clinical data are routinely collected. As of September 2023, PRO data have been collected from 993 patients across 25 different centers. With the goal of incorporating these important patient perspectives into standard clinical care, the CIBMTR has added the PRO data to Data Back to Centers (DBtC). Through expanding the data types represented in the registry, the CIBMTR aims to support holistic research accounting for the patients' perspective in improving patient outcomes. CIBMTR PRO data aim to provide a foundation for future large-scale, population-level evaluations to identify areas for improvement, emerging disparities in access and health outcomes (eg, by age, race, and ethnicity), and new therapies that may impact current treatment guidelines. Continuing to collect and grow the PRO data is critical for understanding these changes and identifying methods for improving patients' quality of life.

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis.

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4-52.8) and the probability of overall survival was 63.8% (95% CI 54.4-72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5-15.4) and 47.3% (95% CI 38.2-56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.

Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival.

PURPOSE: Prognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004). METHODS: Four hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10-5 to 10-6. The primary objective was to assess MRD-negative (MRDneg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS). RESULTS: Similar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRDneg at all three time points was associated with significantly improved PFS, and MRDneg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRDneg patients at BL, PM, and Y1 of 1.55 (P = .0074), 1.83 (P = .0007), and 3.61 (P < .0001), respectively. Corresponding HRs for OS were 1.19 (P = .48), 0.88 (P = .68), and 3.36 (P < .001). Patients with sustained MRDneg or who converted to MRDneg by Y1 had similar PFS/OS. CONCLUSION: To our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRDneg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS.

Advances in long-read single-cell transcriptomics.

Long-read single-cell transcriptomics (scRNA-Seq) is revolutionizing the way we profile heterogeneity in disease. Traditional short-read scRNA-Seq methods are limited in their ability to provide complete transcript coverage, resolve isoforms, and identify novel transcripts. The scRNA-Seq protocols developed for long-read sequencing platforms overcome these limitations by enabling the characterization of full-length transcripts. Long-read scRNA-Seq techniques initially suffered from comparatively poor accuracy compared to short read scRNA-Seq. However, with improvements in accuracy, accessibility, and cost efficiency, long-reads are gaining popularity in the field of scRNA-Seq. This review details the advances in long-read scRNA-Seq, with an emphasis on library preparation protocols and downstream bioinformatics analysis tools.

Adverse events following Covaxin administration among adolescents (15-18 years) - A pharmacovigilance study in a district in Northern India.

Introduction: The study was undertaken to observe the adverse event following immunization (AEFI) to the Covaxin vaccine in young adolescents in the age group of 15-18 years in a district in Northern India. The study was conducted to assess the safety profile of the COVAXIN vaccine. Methodology: This was a prospective observational study conducted at rural and urban health centers of a district in Northern India. We included the beneficiaries of the COVAXIN between the age of 15 and 18 years. The administration of the COVAXIN occurred in our district from January 2022. Periodic visits were conducted to the urban and rural health centers of the city to record any suspected adverse drug reaction following immunization in the defined population. The study was conducted for a period of 1 year (January 2022 to December 2022). Results: A total of 72,771 adolescents (15-18 years) received the first dose of Covaxin and 49,046 received the second dose. No adverse drug event following immunization was reported during the study. Conclusion: Thus, it can be concluded that Covaxin was found to be safe in adolescents (15-18 years).

Pozelimab, a human monoclonal immunoglobulin for the treatment of CHAPLE disease.

The complement is a crucial factor of the innate immune system. However, its activation can lead to various diseases, so it needs to be controlled. In mammals, surface-bound complement regulatory proteins safeguard cells from uncontrolled complement-mediated lysis. One of the human complement regulators is CD55, also known as the decay-accelerating factor (DAF), a single-chain, type I cell surface protein anchored to glycosylphosphatidylinositol (GPI). The genetic loss of the complement regulatory protein CD55 leads to a fatal illness known as CHAPLE disease. The complement and innate immunity become hyperactive in this disease, causing angiopathic thrombosis and protein-losing enteropathy. Patients with CHAPLE disease experience abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and swelling. This genetic condition has no known cure, and managing its symptoms can be challenging. Pozelimab, a human monoclonal immunoglobulin IgG4 antibody, is a drug that targets the terminal complement protein C5. The drug has a high affinity for both wild-type and variant human C5. Pozelimab has received designations such as fast track, orphan drug, and rare pediatric disease, making it a significant medical breakthrough. It is currently the only available treatment for this disease. In this review, we have summarized the preclinical and clinical data on pozelimab.

Non-lesional epilepsy does not necessarily convey poor outcomes after invasive monitoring followed by resection or thermal ablation.

OBJECTIVE: We aimed to compare outcomes including seizure-free status at the last follow-up in adult patients with medically refractory focal epilepsy identified as lesional vs. non-lesional based on their magnetic resonance imaging (MRI) findings who underwent invasive evaluation followed by subsequent resection or thermal ablation (LiTT). METHODS: We identified 88 adult patients who underwent intracranial monitoring between 2014 and 2021. Of those, 40 received resection or LiTT, and they were dichotomized based on MRI findings, as lesional (N = 28) and non-lesional (N = 12). Patient demographics, seizure characteristics, non-invasive interventions, intracranial monitoring, and surgical variables were compared between the groups. Postsurgical seizure outcome at the last follow-up was rated according to the Engel classification, and postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Statistical analyses employed Fisher's exact test to compare categorical variables, while a t-test was used for continuous variables. RESULTS: There were no differences in baseline characteristics between groups except for more often noted PET abnormality in the lesional group (p = 0.0003). 64% of the lesional group and 57% of the non-lesional group received surgical resection or LiTT (p = 0.78). At the last follow-up, 78.5% of the patients with lesional MRI findings achieved Engel I outcomes compared to 66.7% of non-lesional patients (p = 0.45). Kaplan-Meier curves did not show a significant difference in seizure-free duration between both groups after surgical intervention (p = 0.49). SIGNIFICANCE: In our sample, the absence of lesion on brain MRI was not associated with worse seizure outcomes in adult patients who underwent invasive intracranial monitoring followed by resection or thermal ablation.

Effectiveness of interpersonal psychotherapy in comparison to other psychological and pharmacological interventions for reducing depressive symptoms in women diagnosed with postpartum depression in low- and middle-income countries: A systematic review.

Background: Postpartum depression (PPD) is a condition that can affect any woman regardless of ethnicity, age, party, marital status, income, and type of delivery. This condition is highly prevalent worldwide. PPD, if not treated timely, can affect the maternal-child bond and can have a detrimental impact on the future cognitive, emotional, and behavioral development of the child. Interpersonal psychotherapy (IPT) has been reported as an effective treatment of PPD in previous studies as this focuses on relationship and social support issues. Previous reviews conducted in developed nations have reported the superior efficacy of IPT in comparison to other treatment options. There is no systematic review conducted in low to middle-income countries on the efficacy of IPT on PPD. Therefore it was necessary to undertake a systematic review to assess the effectiveness of IPT in reducing the depression among postpartum women in low and middle-income countries (LMICs). Objectives: The main aim of this systematic review was to assess the effectiveness of IPT alone or in conjunction with pharmacological therapy and/or other psychological and psychosocial interventions, in reducing depressive symptoms among women diagnosed with PPD residing in LMICs. Search Methods: The systematic search encompassed several prominent databases and grey literature. Furthermore, experts specializing in the field of IPT were consulted to identify any relevant studies conducted in LMICs that fulfilled the predetermined eligibility criteria. The most recent search update was performed in July 2022. Selection Criteria: The PICOS criteria were meticulously defined for this review as described. Participants: Postpartum women diagnosed with PPD in LMICs were included. Intervention: IPT either as a standalone treatment or in conjunction with pharmacological therapy was included. Comparison: any form of psychological therapy or pharmacological therapy, whether administered individually or in combination, was considered for comparison. Study designs: experimental and quasi-experimental, factorial designs, and quantitative components (experimental, quasi-experimental, factorial designs) of mixed methods designs were eligible to be included. Studies with single-group study designs and qualitative studies were excluded from the review. Data Collection and Analysis: Two reviewers from our team conducted a rigorous screening process to determine the eligibility of articles for inclusion. This involved an initial evaluation of titles and abstracts, followed by a comprehensive assessment of the full text of selected articles. In instances where discrepancies arose between the two reviewers, resolution was achieved through discussion or consultation with a third author to establish a consensus. Following the screening process, two team members independently extracted pertinent information and data from the studies that met the inclusion criteria. The treatment effect of the intervention, in comparison to the control group, was subsequently analyzed utilizing the fixed effects model taking into account the small number of studies. Main Results: A total of 17,588 studies were identified from various databases, and 6493 duplicate studies were removed. Subsequently, 9380 studies underwent independent title and abstract screening resulting in the exclusion of 9040 studies. 345 full texts were thoroughly assessed leading to the exclusion of 341 studies, finally including 4 studies for review. The four included trials were randomized trials and comprised a total sample size of 188 women diagnosed with PPD residing in LMICs. Among these studies, three compared IPT with usual treatment, while one study compared IPT with antidepressant medications (ADMs). In terms of the providers of IPT, in one study, IPT was administered by nurses, while psychologists delivered IPT in another study. In one study, community health workers were responsible for providing IPT. However, in one study, information regarding the specific providers of IPT was not available or reported. The primary outcome measure reported in all four studies was depression, assessed using the Edinburgh Postnatal Depression Scale (EPDS). The geographical distribution of the studies included; one conducted in Zambia, one in Kenya, one in Pakistan, and one in Iran. Out of the four studies, three were included in the meta-analysis, as missing data from one study could not be obtained. Based on the overall treatment effect, it was found that depression scores decreased significantly more in the IPT group compared to other interventions (usual treatment or ADMs) (standardized mean difference [SMD] -0.62, 95% confidence interval [CI] (-1.01, -0.23), Z = 3.13 (p = 0.002), χ 2 = 49.49; df = 2; p < 0.00001; I 2 = 96%; 3 studies, n = 136). Out of the three studies, two studies compared the effectiveness of IPT in reducing depression scores specifically when compared to the usual treatment, and in both studies, depression scores were reduced significantly in the IPT group as compared to the usual treatment group. Only one study directly compared the effectiveness of IPT with ADM, reporting that IPT was more effective than ADM in reducing depression scores among postpartum women. Regarding adverse outcomes, only one study reported suicidal ideation with one participant in the IPT group and two in the ADM group (RR 0.50, 95% CI (0.05, 5.30), p = 0.56, n = 78). The same study reported seven participants in the ADM group had adverse drug reactions as compared to none in the IPT group (RR 15.0, 95% CI (0.89, 254), p = 0.06, n = 78). Authors' Conclusions: Our comprehensive search yielded a limited number of four studies conducted in such settings. Despite the scarcity of available evidence, the findings collectively suggest that IPT is indeed an effective treatment for reducing PPD when compared to usual treatment and pharmacological therapy. However given the low certainty of evidence, there is a need for further research in the form of well-designed randomized controlled trials with larger sample sizes and a reduced risk of bias. Such studies would greatly contribute to enhancing the strength and reliability of the evidence base regarding the effectiveness of IPT in the context of PPD in LMICs. The knowledge generated from future research endeavors would be highly valuable in guiding the development of more affordable and cost-effective treatment approaches for PPD in resource-limited settings.

Purification, kinetic characterization of thermostable multicopper oxidase from the oyster mushroom and its versatility for greener agro-pulp bio bleaching in the paper industry.

Production of a thermostable laccase from Pleurotus florida was reported for the first time, both in submerged and solid-state fermentation using agro-industrial residues. This enzyme was purified using ammonium sulphate precipitation (60-90%), Sephadex G-100 and DEAE column ion exchange chromatography, respectively. The laccase was purified to 21.49 fold with an apparent molecular weight of 66 kDa and had an optimal pH of 5 with temperature stability at 60°C. Metal ions such as Cu2+ (91.26 µmole/mL/min), Mg2+ (68.15 µmole/mL/min), and Fe2+ (1.73 µmole/mL/min) enhanced the laccase activity, but Fe2+ (1.73µmole/mL/min) inhibited the enzyme activity. The purified laccase had Km and Vmax of 16.68 mM and 26.73 µmole/mL/min for guaiacol as a substrate. The isolated enzyme was characterized by FT-IR which revealed bands at 3655.0 cm-1, 2894.7 cm-1, and 1151.7 cm-1 corresponding to primary amines, C-H stretch, and amide -III, respectively. The enzymatic bio bleaching of paddy straw pulp was found to be most effective which resulted in a lowering of kappa number and yellowness by 19.47% & 17.84% whereas an increase in brightness and whiteness by 41.92%. & -19.61%. Thus, this might be stated that the crude laccase from P. florida can be exploited to reduce the toxic waste load for managing environmental pollution and helps in enhancing the yield and quality of the paper.

A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.

BACKGROUND: Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health. CURRENT EVIDENCE: Currently under development, multi-receptor agonist drugs may offer a promising solution to meet this unmet medical need. Retatrutide is a novel triple receptor agonist peptide that targets the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). This novel drug has the potential to treat metabolic abnormalities associated with obesity as well as diseases resulting from it due to its distinct mechanism of action. The Phase III trial of this pipeline drug for treating type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity started on August 28, 2023. The results of a Phase II clinical trial have demonstrated significant weight reduction in overweight and obese adults. Specifically, the trial reported an average weight loss of 17.5% and 24.4% at 24 and 48 weeks, respectively. CONCLUSIONS: These findings hold promise for the development of effective weight loss interventions in this population group. There is a need for more phase III studies to provide sufficient clinical evidence for the effectiveness of retatrutide, as current evidence is limited to phase II studies and has yet to prove its worth in a larger population. Here, we aimed to provide an overview of retatrutide's safety and effectiveness in treating obesity.

Renal Cell Carcinoma Metastasis to the Small Bowel: A Rare Finding 10 Years After Nephrectomy.

Renal cell carcinoma (RCC) most commonly metastasizes to the lung, lymph nodes, bone, and liver. RCC metastasizing to the small bowel is exceedingly rare (0.7%), and the ileum is the least likely site. We discuss the case of a 63-year-old male patient who presented with melena and a 10-kg unintentional weight loss in the preceding month 10 years after undergoing curative nephrectomy for RCC; he was found to have an ileal mass on CT imaging. He subsequently underwent a diagnostic gastroscopy and laparoscopy, later converted to a laparotomy, with bowel resection and anastomosis. The immunohistochemistry was consistent with RCC. This case report highlights the need for awareness about this rare but potential site of metastasis, which may present with gastrointestinal bleeding.

Effectiveness of a school-based behavioural change intervention in reducing chronic disease risk factors in Chandigarh, India: a cluster-randomised controlled trial.

Background: Early behavioural risk factors such as unbalanced diets, physical inactivity and tobacco and alcohol consumption lead to chronic diseases in later life. We conducted a cluster-randomised controlled trial to measure the effect of a school-based health-promotion intervention in reducing the behavioural risk factors of chronic diseases. Methods: Twelve public schools in the Chandigarh, India were randomised to the intervention and control arm. Adolescents studying in eighth grade (n = 453), their parents (n = 395) and teachers (n = 94) were recruited for the current study. The Precede-Proceed Model was followed for intervention development. Intervention in each cluster comprised of one classroom session, four physical activity (PA) sessions every week for adolescents and four separate sessions for parents and teachers. Primary outcomes were eight binary or continuous measures of behavioural risk factors among adolescents (n = 359). Physical Activity Questionnaire-Adolescents (PAQ-A) scores were used to estimate physical activity. The ANCOVA based on cluster proportions or means was used to estimate the intervention effect accounting for baseline data. Findings: Among adolescents, the intervention reduced salt intake by 0.5 g/d (95% CI: -0.9, -0.1), proportion of current alcohol users by 5% (95% CI: -9, -0.007), and increased fruit consumption by 18 g/d (95% CI: 5, 30) and PA by 0.2 PAQ-A score (95% CI: 0.07, 0.3). However, the intervention had no effect on the sugar and vegetable intake and on smokers and tobacco chewers. Exploratory analysis revealed that among parents, PA increased by 205 metabolic equivalents task (MET) units (95% CI: 74.5, 336), fruits intake by 20 g/d (95% CI: 6, 34), and vegetable intake by 117 g/d (95% CI: 50.5, 183). Whereas salt consumption decreased by 0.5 g/d (95% CI: 0.15, 0.9) and the proportion of current alcohol users declined by 5% (95% CI: 9, -1) among parents. Vegetable consumption increased by 149 g/d (95% CI: 12, 286) among teachers. Interpretation: The intervention package implemented among adolescents by involving parents and teachers is an effective model for school-based behaviour-change interventions. Funding: MK received partial funding from the George Institute for Global Health, Hyderabad, India for the salt-reduction component of the study.

Understanding the diabetes self-care behaviour in rural areas: Perspective of patients with type 2 diabetes mellitus and healthcare professionals.

BACKGROUND: Diabetes self-care behaviour plays a crucial role in managing the diabetes effectively and preventing complications. Patients with type 2 diabetes mellitus (T2DM) and health care professionals (HCPs) of rural areas often face unique challenges when it comes to diabetes self-care practices (SCPs). Therefore, this study aim to explore the perspectives of patients with T2DM and HCPs on diabetes SCPs. METHODS: Eight focus group discussions (FGDs) among individuals with T2DM and In-depth interviews (IDIs) with 15 HCPs were conducted in rural areas of Punjab, North India. Capability, Opportunity, Motivation, and Behaviour model (COM-B) was employed for thematic framework analyses. RESULTS: The study participants perceived that a limited understanding of diabetes mellitus (DM), beliefs in alternative therapies, drug side effects, attitudes towards DM (psychological capability), comorbidities (physical capability), family support (social opportunity), financial and time constraints, and weather conditions (physical opportunity) contributed to lack of DM SCPs. Physicians' guidance and support were motivating them to adhere to SCPs, especially when aligned with their sense of self-efficacy (reflective motivation). HCPs constraints in providing patient-centred care are due to training limitations (psychological capability) and a lack of essential resources (physical opportunities). Participants expressed need for comprehensive diabetes care (automatic motivation) through structured diabetes education intervention to improve diabetes SCPs. CONCLUSIONS: The study findings indicate that various factors influence diabetes SCPs from the perspectives of both patients with T2DM and HCPs and emphasizes the need for a multi-faceted approach to improve diabetes SCPs in rural areas. Implementing a structured diabetes self-care intervention strategy in rural areas may help for preventing and mitigating the impact of diabetes-related complications in rural areas.

Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals.

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively. These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.

Effect of health promotion interventions on small portion size consumption behavior among college students.

Background: Large food portion size is contributing toward overweight and obesity rates and has been found directly proportional to increase in portion size. Objectives: The study was done to see the effect of health promotion intervention on small portion size consumption behavior using multitheory model (MTM). Materials and Methods: A quasi-experimental study was conducted among students of age groups 18 - 21 years in two different colleges from North India between 2019 to 2020. About 150 participants in the intervention group as well as control group were selected and health promotion intervention in the form of motivational group counseling, one-to-one counseling, Power Point presentations, lectures, and messages were given to participants in intervention group. Difference in difference of proportions for meal consumption behavior and the difference in the difference of means for body mass index, waist-hip ratio and for constructs of MTM for portion size consumption behavior were calculated. Paired t-test was used to test the significance between the continuous variables. Results: There was a significant reduction (46% vs. 11%, P < 0.001) in proportion of participants consuming large portion-sized meals in the intervention group as compared to the control group. The mean change in constructs (participatory dialogues,behavioral confidence, change in physical environment, emotional transformation and practice for change) for portion size consumption behavior of participants in the intervention and control groups at base line and end line was found statistically significant. Conclusion: MTM is a useful tool for health promotion and health education to predict the initiation and sustenance of health behavior change.

Impact of manures and fertilizers on yield and soil properties in a rice-wheat cropping system.

The use of chemical fertilizers under a rice-wheat cropping system (RWCS) has led to the emergence of micronutrient deficiency and decreased crop productivity. Thus, the experiment was conducted with the aim that the use of organic amendments would sustain productivity and improve the soil nutrient status under RWCS. A three-year experiment was conducted with different organic manures i.e. no manure (M0), farmyard manure @ 15 t ha-1 (M1), poultry manure @ 6 t ha-1(M2), press mud @ 15 t ha-1(M3), rice straw compost @ 6 t ha-1(M4) along with different levels of the recommended dose of fertilizer (RDF) i.e. 0% (F1), 75% (F2 and 100% (F3 in a split-plot design with three replications and plot size of 6 m x 1.2 m. Laboratory-based analysis of different soil as well as plant parameters was done using standard methodologies. The use of manures considerably improved the crop yield, macronutrients viz. nitrogen, phosphorus, potassium and micronutrients such as zinc, iron, manganese and copper, uptake in both the crops because of nutrient release from decomposed organic matter. Additionally, the increase in fertilizer dose increased these parameters. The system productivity was maximum recorded under F3M1 (13,052 kg ha-1) and results were statistically identical with F3M2 and F3M3. The significant upsurge of macro and micro-nutrients in soil and its correlation with yield outcomes was also observed through the combined use of manures as well as fertilizers. This study concluded that the use of 100% RDF integrated with organic manures, particularly farmyard manure would be a beneficial resource for increased crop yield, soil nutrient status and system productivity in RWCS in different regions of India.