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.

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.

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.

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.

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.

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.

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.

Role of calcium &/or vitamin D supplementation in preventing osteoporotic fracture in the elderly: A systematic review & meta-analysis.

Background & objectives: Calcium and vitamin D, separately or in combination are usually prescribed to prevent fragility fractures in elderly population. However, there are conflicting results regarding the ideal dosage and overall efficacy obtained from randomized controlled trials (RCTs) conducted in the past. The objective of this study was to assess the fracture risk with the administration of calcium or vitamin D alone or in combination in elderly population (>60 yr). Methods: PubMed, Cochrane and Embase databases were searched to identify the studies from inception to February 2021 with keywords, 'vitamin D', 'calcium' and 'fracture' to identify RCTs. The trials with comparing vitamin D, calcium or combination with either no medication or placebo were included for final analyses. The data were extracted and the study quality was assessed by two reviewers. The principal outcome measure was fractures around hip joint and secondary outcomes assessed were vertebral and any other fracture. Results: Eighteen RCTs were considered for the final analysis. Neither calcium nor vitamin D supplementation was associated with risk of fractures around hip joint [risk ratio (RR) 1.56; 95% confidence interval (CI), 0.91 to 2.69, I[2]=28%; P=0.11]. In addition, the combined administration of calcium and vitamin D was also not associated with fractures around the hip joint in comparison to either no treatment or placebo. The incidence of vertebral (RR 0.95; 95% CI, 0.82 to 1.10, I[2]=0%; P=0.49) or any other fracture (RR 0.83; 95% CI 0.65 to 1.06, I[2]=0%; P=0.14) was not significantly associated with the administration of calcium and vitamin D either individually or in combination. Further subgroup analysis of the results did not vary with the dosage of calcium or vitamin D, dietary calcium intake sex, or serum 25-hydroxyvitamin D levels. Interpretation & conclusions: The present meta-analysis of RCTs on calcium, vitamin D or a combination of the two in comparison to no treatment or placebo did not support the routine administration protocol of calcium and vitamin D either alone or in combination to lower the risk of fractures in elderly population.

Impact of thiotepa dose-intensity in primary diffuse large B-cell lymphoma of the central nervous system undergoing autologous hematopoietic cell transplant with thiotepa/carmustine conditioning.

Thiotepa/carmustine (TT-BCNU) is a commonly used autologous transplant (ASCT) conditioning regimen for primary DLBCL of the CNS (PCNSL). The total thiotepa dose varies among TT-BCNU recipients, with some centers administering a total dose of 20 mg/kg, while others using 10 mg/kg. We retrospectively assessed the impact of thiotepa dose intensity on ASCT outcomes in 218 adult PCNSL patients who underwent a first ASCT with TT-BCNU conditioning and received either a total thiotepa dose of 10 mg/kg (TT-10 group; N = 90), or 20 mg/kg (TT-20 group; N = 128). The median follow-up of survivors was 22 months. The cumulative incidence of 1-year non-relapse mortality (NRM) for TT-10 and TT-20 cohorts were 6% (95%CI = 2-12%) vs. 4% (95%CI = 1-8%), respectively (p = 0.66). The 3-year cumulative incidence of relapse (15% vs. 13%; p = 0.67), progression-free survival (PFS) (71% vs. 80%; p = 0.25) and overall survival (OS) (79% vs. 83%; p = 0.56) were similar in the TT-10 and TT-20 groups, respectively. On multivariate analysis compared to TT-10, the TT-20 cohort was not associated with significantly different risk of NRM (Hazard ration [HR] = 0.77; p = 0.64), relapse/progression (HR = 0.87; p = 0.74), PFS (HR = 0.80; p = 0.48) or OS (HR = 1.10; p = 0.80). In conclusion thiotepa dose-intensity in TT-BCNU conditioning does not impact ASCT outcomes of PCNSL patients.

Evaluation of EuroQol Valuation Technology (EQ-VT) Designs to Generate National Value Sets: Learnings from the Development of an EQ-5D Value Set for India Using an Extended Design (DEVINE) Study.

INTRODUCTION: Countries develop their EQ-5D-5L value sets using the EuroQol Valuation Technology (EQ-VT) protocol. This study aims to assess if extension in the conventional EQ-VT design can lead to development of value sets with improved precision. METHODS: A cross-sectional survey was undertaken in a representative sample of 3,548 adult respondents, selected from 5 different states of India using a multistage stratified random sampling technique. A novel extended EQ-VT design was created that included 18 blocks of 10 health states, comprising 150 unique health states and 135 observations per health state. In addition to the standard EQ-VT design, which is based on 86 health states and 100 observations per health state, 3 extended designs were assessed for their predictive performance. The extended designs were created by 1) increasing the number of observations per health state in the design, 2) increasing the number of health states in the design, and 3) implementing both 1) and 2) at the same time. Subsamples of the data set were created for separate designs. The root mean squared error (RMSE) and mean absolute error (MAE) were used to measure the predictive accuracy of the conventional and extended designs. RESULTS: The average RMSE and MAE for the standard EQ-VT design were 0.055 and 0.041, respectively, for the 150 health states. All 3 types of design extensions showed lower RMSE and MAE values as compared with the standard design and hence yielded better predictive performance. RMSE and MAE were lowest (0.051 and 0.039, respectively) for the designs that use a greater number of health states. Extending the design with inclusion of more health states was shown to improve the predictive performance even when the sample size was fixed at 1,000. CONCLUSION: Although the standard EQ-VT design performs well, its prediction accuracy can be further improved by extending its design. The addition of more health states in EQ-VT is more beneficial than increasing the number of observations per health state. HIGHLIGHTS: The EQ-5D-5L value sets are developed using the standardized EuroQol Valuation Technology (EQ-VT) protocol. This is the first study to empirically assess how much can be gained from extending the standard EQ-VT design in terms of sample size and/or health states. It not only presents useful insights into the performance of the standard design of the EQ-VT but also tests the potential extensions in the standard EQ-VT design in terms of increasing the health states to be directly valued as well as the number of observations recorded to predict the utility value of each of these health states.The study demonstrates that the standard EQ-VT design performs good, and an extension in the design of the standard EQ-VT can lead to further improvement in its performance. The addition of more health states in EQ-VT is more beneficial than increasing the number of observations per health state. Extending the design with inclusion of more health states marginally improves the predictive performance even when the sample size was fixed at 1,000.The findings of the study will streamline the systematic process for generating precise EQ-5D-5L value sets, thus facilitating the conduct of credible, transparent, and robust outcome valuation in health technology assessments.

Heterotopic sites of pleomorphic adenoma.

The majority of the tumours occurring in minor salivary glands are malignant with only 18% being benign. Among the benign tumours, pleomorphic adenoma is the most common. Although it presents more commonly in the parotid and submandibular glands, it can occur at any site where salivary glands reside. Only 6.4% of cases of pleomorphic adenoma occur in minor salivary glands, e.g. palate, cheeks, lips, para-pharyngeal space, etc. It occurs in females in the fourth or fifth decade. It presents as an asymptomatic and slow-growing mass. The treatment of choice is wide local excision due to the high rate of recurrence and malignant potential. We present rare case reports of two patients. The first case is of a young 18 years female presenting with recurrent neck (anterior triangle) swelling and the second case is of a 46-year-old female presenting with lower lip swelling. In both cases, it was a slow-growing mass and asymptomatic. Cytological examination of the lesion revealed the diagnosis of pleomorphic adenoma. It was completely excised with no post-operative complication. Pleomorphic adenoma, although a common benign neoplasm of major salivary glands, should always be kept as a possibility at the locations of minor salivary glands. As pleomorphic adenoma can transform into a malignant counterpart, therefore early diagnosis and treatment of the lesion can prevent further complications. The prognosis of pleomorphic adenoma is excellent. However, a close follow-up of the patient is required due to the high rate of recurrence.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

A cross-sectional study on COVID-19 vaccine hesitancy at peri-urban areas in Kanpur, Uttar Pradesh, India.

Vaccination is a potential public health solution for the prevention of infection. It reduces the severity of symptoms in case of COVID-19. Despite the availability of vaccines, some people are hesitant to be vaccinated. The objectives of the study were to measure the proportion of vaccine hesitancy among the peri-urban population and identify its determinants. An adult population of 303 from two peri-urban areas in the field practice area of Urban Health Training Centre, Rama Medical College were interviewed from 22nd February 2021 to 25th March 2021. Epicollect 5 was used for collecting data and STATA 16 was used for analysis. Multivariable logistic regression was applied to compute the adjusted odd ratio (95% confidence interval) to find out the determinants of vaccine hesitancy. Three Cs model guided tools of data collection and analyses. More than one fourth (28%) of the participants were vaccine-hesitant whereas 34.6% of participants had no confidence in the vaccine. Other reasons were complacency (40.6%) and convenience (35.9%). Vaccine hesitancy was significantly associated with gender [AOR = 2.40 (1.12-5.16)] and trust in government [AOR = 0.18 (0.08-0.45)] but no association with age group, political affiliation and source of information about the vaccine.  It is important to build the trust of people in vaccines, make it convenient and resolve the issues that are making them complacent. The health system needs to involve non-governmental organisations to reach out to those for whom there are issues of availability and approach.

Minerals and chelated-based manganese fertilization influences the productivity, uptake, and mobilization of manganese in wheat (Triticum aestivum L.) in sandy loam soils.

Manganese (Mn) is an essential micronutrient in plants, and it is necessary for hydrolysis in photosystem II, chlorophyll biosynthesis, and also chloroplast breakdown. Limited Mn availability in light soil resulted in interveinal chlorosis, poor root development, and the development of fewer tillers, particularly staple cereals including wheat, while foliar Mn fertilizers were found efficient in improving crop yield as well as Mn use efficiency. In the above context, a study was conducted in consecutive two wheat growing seasons for screening of the most effective and economical Mn treatment for improving the yield and Mn uptake in wheat and to compare the relative effectiveness of MnCO3 against the recommended dose of MnSO4 for wheat. To fulfill the aims of the study, three manganese products, namely, 1) manganese carbonate MnCO3 (26% Mn w/w and 3.3% N w/w), 2) 0.5% MnSO4·H2O (30.5% Mn), and 3) Mn-EDTA solution (12% Mn), were used as experimental treatments. Treatments and their combinations were as follows: two levels of MnCO3 (26% Mn) @ 750 and 1,250 ml ha-1 were applied at the two stages (i.e., 25-30 and 35-40 days after sowing) of wheat, and three sprays each of 0.5% MnSO4 (30.5% Mn) and Mn-EDTA (12% Mn) solution were applied in other plots. The 2-year study showed that Mn application significantly increased the plant height, productive tillers plant-1, and 1,000 grain weight irrespective of fertilizer source. The results of MnSO4 for grain yield wheat as well as uptake of Mn were statistically at par with both levels (750 and 1,250 ml ha-1) of MnCO3 with two sprays at two stages of wheat. However, the application of Mn in the form of 0.5% MnSO4·H2O (30.5% Mn) was found more economical than MnCO3, while the mobilization efficiency index (1.56) was found maximum when Mn was applied in MnCO3 with two sprays (750 and 1,250 ml ha-1) in the two stages of wheat. Thus, the present study revealed that MnCO3 can be used as an alternative to MnSO4 to enhance the yield and Mn uptake of wheat.

Theory-guided process evaluation of a multicomponent, technology-based 'SMART Eating' trial among Indian adults: an embedded mixed-methods study.

We report process evaluation findings from the 'SMART Eating' intervention trial, which significantly improved fat, sugar and salt (FSS), and fruits and vegetables (FVs) intake among adults. Intervention used information technology [short message service (SMS), WhatsApp and website] and interpersonal communication (distribution of SMART Eating kit) and pamphlet for comparison group. Guided by UK Medical Research Council's framework, using embedded mixed-methods design, continuous process evaluation documented fidelity, dose, reach, acceptability and mechanisms. Intervention was implemented as intended, with high reach (91%) in both groups: 'comparison group' (n = 366): inadequate use of pamphlets (46%); 'intervention group' (n = 366): with timely remedial measures to remove implementation/usage barriers, dose of SMS (93%), WhatsApp (89%) and 'SMART Eating' kit (100%) was adequate, but website usage was low (50%); compliance was evident from participants' interactions with the implementor and observations on kit usage. All these might have improved attitude, social influence, self-efficacy and household behaviours, which, in turn, mediated intervention's effect on improving FSS and FV intake. Among poor performers, lack of effect on FV intake was perceived to be related to high cost/pesticides use and FSS intake was related to lack of family support. Low website usage, challenges with WhatsApp messaging and contextual factors (cost, pesticides abuse and family support) need to be considered while designing similar future interventions.

Impact of Community Based Nutrition Intervention in the Prevention and Control of Anaemia Among Reproductive Aged Women of India.

INTRODUCTION: Maternal and child under-nutrition is particularly widespread in low and middle-income nations, increasing the overall disease burden due to poor nutritional status. The aim of this study was to develop nutrition intervention for the prevention and control of anaemia among women of reproductive age. METHODS: Community-based intervention study was conducted among 443 women of reproductive age group (15-49 years) to determine the effectiveness of a 6-month nutrition intervention package. The nutrition intervention was developed by using Precede-Proceed model and the trans-theoretical model of behavior change. Multi-channel communication approach was adopted and nutrition intervention package was provided. Assessment of haemoglobin, red blood cells, platelet, ferritin, folate, vitamin B12, haematocrit test, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width and total leucocyte count was compared at the baseline and endline after the intervention among the participants. The chi-square test of independence and t-test were performed. RESULTS: The only mean ferritin level shows significant improvement (p < 0.001). A significant decrease (~ 15%, p = 0.027) in anaemia was observed after the intervention. CONCLUSIONS: Improvement in anaemic status of women was observed. National schemes and programs require a more robust strategical implementation like food fortification/bio fortification and behaviour change communication at village level to enhance the availability and accessibility of fortified food.