Highly efficient synthesis of isoxazolones and pyrazolones using g-C3N4·OH nanocomposite with their in silico molecular docking, pharmacokinetics and simulation studies.

An environmentally friendly, versatile multicomponent reaction for synthesizing isoxazol-5-one and pyrazol-3-one derivatives has been developed, utilizing a freshly prepared g-C3N4·OH nanocomposite as a highly efficient catalyst at room temperature in aqueous environment. This innovative approach yielded all the desired products with exceptionally high yields and concise reaction durations. The catalyst was well characterized by FT-IR, XRD, SEM, EDAX, and TGA/DTA studies. Notably, the catalyst demonstrated outstanding recyclability, maintaining its catalytic efficacy over six consecutive cycles without any loss. The sustainability of this methodology was assessed through various eco-friendly parameters, including E-factor and eco-score, confirming its viability as a green synthetic route in organic chemistry. Additionally, the gram-scale synthesis verifies its potential for industrial applications. The ten synthesized compounds were also analyzed via a PASS online tool to check their several pharmacological activities. The study is complemented by in silico molecular docking, pharmacokinetics, and molecular dynamics simulation studies. These studies discover 5D as a potential candidate for drug development, supported by its favorable drug-like properties, ADMET studies, docking interaction, and stable behavior in the protein binding cavity.

Predictors of Resolution of Meningitis Symptoms in Tuberculous Meningitis: A Clinical, Magnetic Resonance Imaging, and Biomarker Study.

In tuberculous meningitis (TBM), the meningeal symptoms and their resolution after treatment may be dependent on clinical-radiological severity, cerebrospinal fluid (CSF), and proinflammatory cytokines, and these findings may be associated with outcome. There is a paucity of studies on the resolution of meningitis symptoms in TBM. We report on associations of clinical, magnetic resonance imaging (MRI), laboratory, and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 6 (IL-6)] findings with the resolution of meningitis symptoms (RMS), and the impact of RMS duration on the outcome in TBM. Seventy-one patients with TBM were included, and their clinical, laboratory, and MRI findings at baseline were recorded. mRNA profiling of TNF-α and IL-6 was done by reverse transcriptase polymerase chain reaction. The day of RMS (fever, headache, and vomiting) after treatment was noted. Predictors of long duration of RMS (>3 weeks) were evaluated by univariate followed by multivariate analysis. The impact of RMS on 6-month mortality and outcome was analyzed. Patients' median age was 25 years, and 45 (63.4%) were males. After antitubercular treatment, meningeal symptoms resolved in 35 (50.70%) by 21 days and in 90% of patients by 49 days. Longer time of RMS was associated with TBM stage, pretreatment duration, seizure, and hydrocephalus but not with TNF-α and IL-6. Seven (9.8%) patients died at 6 months, and duration of RMS predicted death (hazard ratio = 25.55, 95% CI: 1.108-589.40; P = 0.04).

Oral cancer in India.

OBJECTIVES: To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of care and monitoring. METHODS: Two national estimates of incidence and mortality were cited, one for 2016 by the Global Burden of Disease India Study and one based on projections for 2020 by GLOBOCAN. The National Cancer Registry Project provided local and regional incidence and trends using data from 2012-2016. Scientific literature, reports of the NCRP, the IARC and government press releases were also consulted. RESULTS: Tobacco and areca nut habits are the major risk factors for OC in India. In the 1980s, intervention studies on oral screening, awareness generation and habit cessation in rural areas reduced tobacco use and oral leukoplakia. Lately, adoption of the tobacco control law and mass media communications have resulted in decreased tobacco use. However, the increasing popularity of highly carcinogenic tobacco products containing areca nut, with evasion of their bans, is increasing OC incidence. CONCLUSION: Despite advances in care, there is growing incidence of OC, persisting poor awareness about the need to quit tobacco/areca nut/alcohol use and go for screening. Major efforts are needed to implement preventive activities.

"The ban is there, but it is not there": perceptions of cigarette users and tobacco vendors regarding ban on the sale of loose cigarettes in India.

Introduction: Banning the sales of loose cigarettes is recommended by Article 16 of the World Health Organization - Framework Convention on Tobacco Control. This study aims to understand the perceptions of cigarette users and tobacco vendors regarding such a ban. Methods: Using a systematic recruitment and interview protocol, we interviewed cigarette users (n = 28) and tobacco vendors (n = 28) from two Indian cities where sales of loose cigarettes were banned (Mumbai) or not banned (Delhi). Separate semi-structured interview guides were used for users and vendors. Interview questions focused on reasons for purchasing loose cigarettes, preference for buying and selling loose vs. packs, thoughts on the necessity of banning loose cigarettes, and the perceived impact of the policy ban for vendors and cigarette users. We performed thematic analysis and used NVivo for organizing transcript coding. Results: The main reasons users cited for purchasing loose cigarettes were financial constraints, social restrictions (fear of getting caught), and limiting cigarette consumption. In Mumbai, awareness of the existing ban was poor among both users and vendors. Those who were aware did not think the policy had been implemented. Users thought that loose cigarettes promoted smoking initiation and prevented them from quitting. Both users and vendors reported that a ban on loose cigarettes would reduce cigarette consumption and promote quit attempts as it would not be possible for everyone to purchase packs because of financial and social reasons. Conclusion: Users in both cities reported easy access to and widespread availability of loose cigarettes. Low awareness of the ban in Mumbai suggested inadequate enforcement. A country-wide ban on the sale of loose cigarettes could be highly effective in preventing smoking initiation and promoting quitting.

Propeller vs. free fasciocutaneous flap in reconstruction of complex lower limb defects-A prospective study.

BACKGROUND: Of all body regions, lower extremity wounds have been and remain the greatest challenge. Free flaps have been accepted as a reasonable option to solve this dilemma, but they require the complexity of microsurgery. This study aimed to compare the postoperative and clinical outcomes of propeller flap and fasciocutaneous free flap in the reconstruction of complex lower limb defects. MATERIALS AND METHODS: This randomized controlled trial was conducted from July 2021 to June 2023. Selected patients were randomized into two groups: the propeller flap group and fasciocutaneous free flap group. Demographic data, preoperative parameters, and postoperative parameter, including esthetic analysis, scar assessment, neurosensory analysis, psychosocial analysis, and lower extremity function, were estimated and statistically significant compared between the two study groups. RESULTS: Road traffic accident (73.3%) was the most common etiology for lower limb defects in both groups. The foot and lower third of the leg were the most common site of defect, constituting 79.99%. The duration of surgery was significantly shorter in propeller flap as compared to fasciocutaneous free flaps. Flap size was smaller, with better neurosensory improvements in propeller flap group. Esthetic analysis, scar assessment, psychosocial analysis, and lower extremity functional analysis yielded similar results in both study groups. CONCLUSION: Propeller flap has better outcomes compared to free flap in terms of smaller size of flap, shorter duration of surgery, and reduced length of hospital stay. Comparable results were obtained with respect to esthetic score, scar assessment score, psychosocial analysis, and neurosensory recovery and lower extremity functional score.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Constructing the scale to measure entrepreneurial traits by using the modified delphi method.

Higher entrepreneurial traits significantly increase the likelihood of graduate students venturing into entrepreneurship. This study intended to develop a scale for assessing the entrepreneurial traits of graduate students, recognizing a gap in existing literature and measurement tools predominantly developed for countries with conducive entrepreneurial climates. Aligned with Ajzen's theory of planned behavior, the study employed a modified Delphi method, including prototype development, two Delphi surveys, and subsequent statistical analyses. The robustness of the final items and scale in effectively capturing the entrepreneurial traits of graduate students is supported by descriptive statistical analyses (SD ≤ 1.5, Interquartile Range ≤1, and Level of Agreement ≥70%), content validity analysis (I-CVI≥ 0.8, S-CVI/Ave = 0.92; S-CVI/UA = 0.4), and Kendall's Coefficient of Concordance analysis (X2 (37, N = 30) = 700.504, W = 0.631, p < 0.01). Ultimately, the scale comprises 38 items organized into three overarching thematic areas: life philosophy, creating and utilizing mindset, and supportive and motivating environment. Consistent with existing literature, entrepreneurial traits are intricately linked to individuals' life perspectives, often characterized by a desire for self-autonomy. Additionally, the ability to create or leverage available resources and the presence of a conducive external environment emerge as pivotal dimensions in entrepreneurial traits. Notably, the study highlights the critical influence of a country's environment and policies, mainly through university courses and short-term programs, in shaping the development of entrepreneurial traits.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Prevalence, Reach of Anti-smokeless Tobacco Messages and Quit Attempts by Product Type: A Secondary Data Analysis from the Global Adult Tobacco Survey (GATS - 2016-17).

OBJECTIVE: India has the highest number of smokeless tobacco (SLT) products available in different forms, consumed in various ways. The current study aimed to understand the pattern of daily SLT use according to different product categories and whether Quit intention and Quit attempts vary by SLT type and exposure to media messages. METHODS: Data from Global Adult Tobacco Surveys (GATS), 2016-17, was used to find access to media messages and warning labels by SLT type. Quit attempt and Quit intention were calculated for each of the SLT types. Logistic regression analyses were employed to identify whether access to media messages, warning labels influenced, quit intention and attempts vary by SLT type. RESULTS: Khaini or tobacco lime mixture was the most common SLT type consumed by 37% of SLT users, whereas SLT users consuming more than one product accounted for 23% of SLT users. Exposure to media messages and warning labels was high among Gutkha/ paan masala tobacco users (74.7% and 81.2%) and low among oral tobacco (Mishri, Gul, Gudakhu) users (56.1% and 60.0%). Quit attempts and quit intention were high among Gutkha/ paan masala tobacco users (38.3% and 22.3%) and low among oral tobacco (Mishri, Gul, Gudakhu) users (25.3% and 13.6%). Users of Oral tobacco and khaini or tobacco-lime mixture were significantly less likely to attempt quitting (AOR 0.806(95%CI: 0.676-0.962), 0.839(95%CI: 0.736-0.956), and have quit intention (AOR 0.681(95%CI: 0.702-0.976), 0.733(95%CI: 0.627-0.857) compared to Gutkha/ paan masala with tobacco users. CONCLUSION: The reach of media messages and warning labels varies by SLT type. Quit intention and attempts vary by SLT type and access to media messages and warning labels. There is a need to re-strategise the tobacco control Information, Education and Communication (IEC) to reach out with effective messaging to the most unreached.

Myositis in H1N1 Infection Compounds to Myasthenic Crisis.

ABSTRACT: Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We report two myasthenia gravis (MG) patients with H1N1 infection, and highlight the reasons for deterioration. Two patients with MG had H1N1 infection. The diagnosis of MG was confirmed by neostigmine, repetitive nerve stimulation, and anti-acetylcholine receptor antibody tests. H1N1 was confirmed by nucleic acid detection study, and myositis by creatinine kinase. The patient with pneumonia and myositis had MC needing mechanical ventilation for 10 days, and the other patient without myositis did not have MC. They were treated with oseltamivir 75 mg twice daily for 5 days, and the patients with MC received ceftriaxone intravenously. Both the patients were on prednisolone and azathioprine, and none received prior H1N1 vaccination. The lady with MC with myositis was discharged on day 27 in wheelchair bound state, and the other one patient without myositis or MC was discharged on 6th day with full recovery. These patients highlight the need for evaluation for myositis along with pneumonia in the MG patients with H1N1 infection. Vaccination in MG patients on immunosuppression may be useful.

MANEC TUMOR OF RECTUM. A RARE CASE SERIES OF 3 PATIENTS AND A LITERATURE REVIEW.

The term Mixed Adeno-Neuro-Endocrine Carcinoma (MANEC) was introduced in 2010 by the WHO Classification of Tumors of the Digestive System. It refers to a neoplasm with dual epithelial and neuroendocrine differentiation, each component representing at least 30% of the tumor. It is an uncommon tumor accounting for < 3% of all colon and rectum malignancies. We report three cases of this extremely rare MANEC of the rectum. All three cases presented with hematochezia, variable constipation, and abdominal pain. They were diagnosed and staged appropriately with colonoscopy, biopsy with immunohistochemistry, and imaging. They underwent an anterior resection with circular stapled anastomoses. Because of the low incidence of this histotype, we reviewed the clinical presentation, diagnostic characteristics, and treatment of MANEC of the colon and rectum.

Evaluation of the effectiveness of the Indian government's policies to strengthen health warning labels on smokeless tobacco products: findings from the 2010-2019 Tobacco Control Project India Surveys.

BACKGROUND: Smokeless tobacco (SLT) packaging in India had a single symbolic (a scorpion) health warning label (HWL) in 2009 covering 40% of the front surface. In 2011, it was replaced with four pictorial images. In 2016, HWLs were enlarged to 85% on the front and back. This study aimed to assess the effectiveness of the old (symbolic and smaller images) and larger HWLs. METHODS: Data were from the Tobacco Control Project India Survey and included respondents who used SLT in Wave 1 (2010-2011, n=5911), Wave 2 (2012-2013, n=5613) and Wave 3 (2018-2019, n=5636). Using a repeated-measures design, weighted logistic regression models assessed whether there were changes in seven HWL effectiveness measures within the domains of awareness, salience, cognitive and behavioural responses. A cohort design was employed to test whether HWL effectiveness in Waves 1 and 2 was associated with quitting SLT in Waves 2 and 3, respectively. RESULTS: The 2011 HWL revision did not result in any significant changes in HWL effectiveness. There was no significant change in HWL awareness and salience after larger HWLs were introduced in 2016, but respondents were more likely to consider SLT health risks (Wave 2=17.9%, Wave 3=33.6%, p<0.001) and quitting SLT (Wave 2=18.9%, Wave 3=36.5, p<0.001). There was no change in HWLs stopping SLT use (Wave 2=36.6%, Wave 3=35.2%, p=0.829); however, respondents were more likely to avoid looking at HWLs (Wave 2=10.1%, Wave 3=40.2%, p<0.001). Effectiveness of older, symbolic and smaller pictorial HWLs was not associated with quitting SLT. DISCUSSION: There was no significant change in HWL effectiveness following the revision from a symbolic to a pictorial image, but enlarging pictorial images resulted in some improved cognitive and behavioural effects. Results suggested wear-out of HWL salience and that the effectiveness of warnings depends on both their design and time since implementation.

Antimony precipitation and removal by antimony hyper resistant strain Achromobacter sp. 25-M.

Microbes have been confirmed to play key role in biogeochemistry of antimony. However, the impact of indigenous bacteria (from active mines) on the behavior of dissolved antimony remained poorly understood. In current study, the hyper antimony-resistant strain, Achromobacter sp. 25-M, isolated from the world largest antimony deposit, Xikuangshan antimony deposit, was evaluated for its role in dissolved Sb(V) and Sb(III) precipitation and removal. Despite of the high resistance to Sb(III) (up to 50 mM), the facultative alkaliphile, 25-M was not capable of Sb(III) oxidation. Meanwhile 25-M can produce high amount of exopolymeric substance (EPS) with the presence of Sb, which prompted us to investigate the potential role of EPS in the precipitation and removal of Sb. To this end, 2 mM of Sb(III) and Sb(V) were added into the experimental systems with and without 25-M to discern the interaction mechanism between microbe and antimony. After 96 hrs' incubation, 88% [1.73 mM (210 mg/L)] of dissolved Sb(V) and 80% [1.57 mM (190 mg/L)] of dissolved Sb(III) were removed. X-ray diffraction and energy dispersive spectroscopy analysis confirmed the formation of valentinite (Sb2O3) in Sb(III) amended system and a solitary Sb(V) mineral mopungite [NaSb(OH)6] in Sb(V) amended group with microbes. Conversely, no precipitate was detected in abiotic systems. Morphologically valentinite was bowtie and mopungite was pseudo-cubic as indicated by scanning electronic microscopy. EPS was subjected to fourier transform infrared (FT-IR) analysis. FT-IR analysis suggested that -OH and -COO groups were responsible for the complexation and ligand exchange with Sb(III) and Sb(V), respectively. Additionally, the C-H group and N-H group could be involved in π-π interaction and chelation with Sb species. All these interactions between Sb and functional groups in EPS may subsequently favore the formation of valentinite and mopungite. Collectively, current results suggested that EPS play fundamental role in bioprecipitation of Sb, which offered a new strategy in Sb bioremediation.

mRNA profiling of cytokines to understand paradoxical response in HIV-uninfected tuberculous meningitis.

Paradoxical reaction (PR) in tuberculous meningitis (TBM) is a major management issue. We report mRNA profiling of cytokines to understand PR in HIV-uninfected TBM patients. 72 patients with TBM were included, and their clinical, MRI, and mRNA profiling of tumor necrosis factor (TNF) α, interleukin (IL) 6, IL10 and interferon (IFN) γ genes in the peripheral blood mononuclear cells were done at admission and 6 weeks of antitubercular treatment. Cytokine profiling was done using reverse transcriptase polymerase chain reaction. PR was defined if repeat MRI at 6 weeks revealed new or increase in exudates, tuberculoma, hydrocephalus or infarctions. Outcome was defined at 6 months using modified Rankin Scale (mRS), and categorized as death, poor and good. 44 (61.1 %) patients had PR, and 28 (38.9 %) had paradoxical tuberculoma (PT). The expression of IL6 and TNFα genes were higher in PR and PT groups. Stage of meningitis and hydrocephalus at admission predicted PR. Patients with PR and PT had more frequently poor outcome. About three-fifth HIV-uninfected TBM patients have PR and two-fifth have PT. Paradoxical reaction is associated with higher expression of IL6 and TNFα. Patients with severe meningitis with hydrocephalus develop PR more frequently.

An Ergonomic Approach For Designing A Seat For Fish Processing Workers

The present study aimed to design a sitting stool for fish processing worker to reduce the postural stress during work. The study was conducted on 74 male and female fish processing workers selected randomly. The Musculoskeletal Disorder (MSD) of the subjects was assessed by the modified Nordic Questionnaire method. The body joint angles were measured by a digital goniometer. The results revealed that MSD was highly prevalent in lower back region in both male (78.57%) and female (93.47%) workers. The results of body joint angles suggested a high degree of forward bending during work. Efforts were made to design a sitting stool considering the human factors of the users to reduce the postural problems. The stool was designed by considering 5th and 95th percentile values of different anthropometric dimensions of the male and female workers. Paired comparison tests were employed to determine optimum dimensions of the stool for ensuring the compatibility of the physical characteristics of the stool with human body. From the results of paired comparison test and anthropometric characteristics of the users, physical dimensions of the sitting stool were settled for final designing. From the results, the height of the stool was determined separately for male and female workers. In the suggested design the height of the seat was 25cm for male and 20cm for female where the length and depth of the seat were 40cm and 32cm respectively for both sexes.A mechanical system was incorporated in the design so that the same stool could be used by the male and female workers. Subjective evaluation indicated that most of the subjects (>75%) rated the seat as good or very good. The joint angle study with suggested seat showed improved working posture.