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Background: Coronavirus disease 19 (COVID-19) has become a global pandemic; its unparalleled speed of spread has left us all in a worldwide alarming situation. Aims: The aim was to study the prevalence of COVID-19 infection in asymptomatic antenatal patients at term and its maternal and fetal outcomes and neonates being followed up till 18 months for developmental assessment. This was a prospective observational study carried out from September 1, 2020, to March 31, 2023. Materials and Methods: This prospective observational study was conducted on 250 pregnant women attending the antenatal care outpatient department in a Zonal Hospital in Northeastern India expected to undergo delivery in the next 5 days, and all suspected COVID-19 pregnant women were included in the study. Asymptomatic pregnant women not expecting delivery in the next 5 days were excluded. All neonates born to these 250 mothers were followed till 18 months of age and were then assessed for the impact of COVID-19 on the developmental milestones. The prevalence of COVID-19 was calculated in the study population. The Chi-square test was used to compare categorical variables in COVID-19-positive and -negative groups. P

Background: During the surge of COVID-19 pandemic, the mechanism of reporting and documentation of deaths was inadequate. It is crucial to establish the mechanism for measuring the actual events of COVID-19 and associated mortalities as well during this pandemic situation. This is the first instance of application of different rapid methods for death estimation during the pandemic situation. If found to be valid, these methods may be useful for other countries with limited resources and less developed death registration system. Objective: To find out the feasibility, acceptability of different rapid method for estimating the cause of deaths among the general population & healthcare workers and also to estimate the number of deaths among allopathic doctors. Methodology: The study was conducted from September 2022 to October 2023. Target population being adult deceased person between 1st April 2020 to 30th November 2022 among general population, health care worker and allopathic doctor. For the general population, the study was conducted in one urban municipal area and two sub-centres of Habra Block I under North 24 Parganas district with WHO Verbal Autopsy (VA) tool for adult. Complete enumeration with snowballing, compartmental and capture-recapture method was adopted for general population, health care worker and allopathic doctor respectively. Results: Overall, 300 VA could be performed (121 urban & 179 rural) among general population. There were challenges related to both feasibility & acceptability in terms of data access, permission and cooperation. Research team employed a combination of persistence, local collaboration, and strategic decision-making to successfully collect data. Acceptability was more in rural area. Total number of deceased doctors was estimated to be 246 from two different lists. Conclusion: Rapid methods may be employed as a part of response systems during pandemic or any future disasters if adequate governmental support and assistance is obtained along with aid from the local people.

Background: Soul of India lives in its villages with >65% population living in rural settings. Saturation of all services especially Health services is at core of “leave no one behind” in line with principle of ‘Antyodaya’ reaching out at all. To build momentum with Pradhan Mantri Jan Arogya Yojana Ayushman Health Camps were organised by IGMC Shimla at secondary level facilities under flagship campaign Ayushman Bhavah Objective: Evaluation of health care services delivered by IGMC Shimla in Ayushmann Health Melas at secondary level facilities of 03 districts of Himachal Pradesh. Methodology: Ayushman Melas organised by IGMC Shimla at secondary level facilities from September 2023 to December 2023 in 03 districts Shimla (25); Solan (12) and Bilaspur (13) for providing clinical services to beneficiaries. Real time portal based reporting and analysis of same alongwith specialitywise footfallbifurcation is core. Results: As per Real time-based portal report analysis a footfall of 10379 registered out of which 9055 (87.24%) availed specialists services and 1324(12.74%) general physician services. A net of 2672 (29.5%) beneficiaries availed internal medicine specialist services, 458 (5.05%) surgical, 1619 (17.87%) orthopaedics, 772 (8.52%) obstetrics and gynaecology, 1460 (16.12%) Opthalmology, 698 (7.7%) Otorhinolaryngology, 152 (1.67%) psychiatry, 493 (5.44%) dermatology and 731 (8.07%) paediatric services respectively. 1012(9.75%) new diagnosed Hypertensives and 945 (9.10%) new diagnosed Diabetics, 1492 14.37%) beneficiaries screened for Oral Cancers, 804 (7.75%) for breast cancers and 468 (4.5%) for cervical Cancers. 299 (2.88%) new diagnosed cataract cases. 10379 beneficiaries were tested for 11102 tests (106.96%). Conclusion: Comprehensive health care service delivery by camps to unreachable for screening, diagnosis, one stop multi-speciality consultancy, referral and digitalisation of health vitals.

Background: Statin therapy is commonly used on the long term in hypertensive patients with dyslipidemia and can interfere with vitamin D metabolism. Overweight/obesity and type 2 diabetes mellitus (DM) are frequently associated with hypertension.

In a number of malignancies, new immuno-oncology therapies that focus on the programmed cell death 1 (PD-1) have improvised the patient condition along with a positive aftereffect. Monoclonal antibodies (mAbs) directed against PD-1 and its ligand (PD-L1), have been widely used to treat a variety of malignancies, including melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Dostarlimab, a therapeutic anti-PD-1 antibody, was authorised by the United States Food and Drug Administration (FDA) in April 2021 under the trade name JEMPERLI. It is a humanised contrary PD-1 immunoglobulin G 4 (IgG4) mAb, which successfully blocks interaction with PD-L1 and PD-L2 by binding tightly to the PD-1 receptor. This article summarizes the different aspects associated with the dostarlimab, including currently available anti-PD-1/PD-L1 antibodies, pharmacokinetics (PK), pharmacodynamics, adverse reaction, and mechanism of action of dostarlimab, as well as various reported clinical trials.

The term 'Honour Killing' is conventionally used to denote a specific category of extralegal killings where the act of murder is seen to have been motivated by pre-modern affiliations/sentiments of some sort. Acts of violence committed against people for marrying outside of caste/religion/ethnicity or other similar infringements where they are seen by their actions to have besmirched the honour of the family and the larger community come under the broad rubric of honour crime. Implicit in using the term are assumptions that mark it as different from other crimes. Honour is defined in terms of women assigned sexual and familial roles as dictated by traditional family ideology. Thus, adultery, premarital relationships (which may or may not include sexual relations), rape, and falling in love with an "inappropriate" person may constitute violations of family honour. 'Crimes of honour' as a form of violence against women does not imply that men also are not subjected to such crimes. In cases of forced marriage or interference with the right of choice and whom to marry, pressure from older family members over younger members will apply to men as well as to women. However, women remain the victims and survivors of 'crimes of honour' and have fewer available remedies.

This study emphasizes the development of a flexible inventory system considering rework requirements on imperfect and defective items. This work has considered defective items could be sold at a lower price in the market as compared to the perfect items. The developed model has considered Weibull deterioration and inflation to balance the same amount in the future due to its potential earning capacity. And demand's function depends on price as well as inventory level because a large pile of goods and their price strategy attracts more customers to generate higher demand. The work also supports managerial decision-making by focusing on the volume flexibility system for smooth production runs. The mathematical formulation of the developed inventory system tries to optimize the inventory cost function under a realistic scenario. A solution procedure has been illustrated and assisted with a numerical example. Later, a validation test is also performed to check the robustness of the proposed mathematical model. The findings of the study will support policymakers, strategists, and firms to implement flexible inventory systems under realistic conditions.

Glucagon-like peptide 1 (GLP-1) receptor agonists have acquired importance in Type 2 diabetes (T2D) treatment due to their glycemic advantages, cardiorenal effects, and favorable body weight. Despite this, the continuous discovery of higher effectiveness treatments is critical to addressing ongoing difficulties in the accomplishment of metabolic targets in many T2D patients. Tirzepatide is a unimolecular dual GLP-1 and Glucose-dependent insulinotropic polypeptide (GIP) receptor agonist that is being developed for the treatment of T2D. Tirzepatide was approved in May 13, 2022 by the United State Food and Drug Administration (USFDA) with the brand name Mounjaro as the first and the only GLP-1 and GIP receptor agonist to treat T2D. This review outlines essential features of tirzepatide including chemistry, synthesis, pharmacology and mechanism of action of tirzepatide as well as pharmacodynamics, pharmacokinetic and reported clinical trials.

Industrial organisations must now develop and implement novel approaches to operations and production if they are to compete effectively on a global scale. Changes in product development practises and the use of new technologies have occurred. Businesses encounter problems and difficulties as a direct result of the rapid pace of market change. Organisational priorities focus on minimising waste while simultaneously improving quality and cutting costs. Lean manufacturing is an established approach that should be included into every strategic company strategy. Lean manufacturing concept is a revolutionary that aims to increase resource use while minimising waste. Lean manufacturing has been shown to increase plant efficiency and decrease processing times in major manufacturing operations. In the end, industries depend greatly on their capacity to systematically and consistently cope with obstacles in order to increase product value. Therefore, a value-adding framework must be implemented; the adoption of a lean manufacturing system becomes crucial for any kind of business if it is to achieve this level of perfection. This article gives a overview of lean manufacturing their concepts, tools with application and artificial intelligence in lean manufacturing.

The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure–activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

This work presents the results from the characterization of a Position-Sensitive Planar Germanium (PSPGe) detector. The PSPGe detector is a double-sided orthogonal strip detector consisting of 10x10 electrical segmentation along the horizontal and vertical directions. The characterization was performed using the coincidence setup between the PSPGe detector and the well-characterized scanning system employing the positron annihilation correlation principle. The scanning system consists of a Position Sensitive Detector (PSD) and 22Na positron source. The main objective of this study is to deploy PSPGe detector for future decay experiments at the Facility for Antiproton and Ion Research (FAIR), Germany. The measurements have been performed to find the depth of gamma-ray interaction in the planar segmented detector. The 2-Dimensional image obtained from the PSD has been used to find the depth of gamma-ray interaction in the planar strip detector using pulse shape analysis. In addition, the sensitivity of PSPGe detector has been investigated by calculating the rise-time from pulse shapes for the front and back strips of the detector.

This study discusses the dispersion equation for SH waves in a non-homogeneous monoclinic layer over a semi-infinite isotropic medium. The wave velocity equation has been obtained. In the isotropic case, when the non-homogeneity is absent, the dispersion equation reduces to a standard SH wave equation. The dispersion curves are depicted by means of graphs for different values of non-homogeneity parameters for the layer and semi-infinite medium.

The loads in rustic area are preeminent pump sets used for various applications i.e. lift irrigation system. Minimal power factor and minimal load factor is found in loads. Further, being a factordissemination of loads, load density is found low. The present distribution system dwell of three-phase 11KV/433Volts distribution transformer with extended L.T Lines. In this system, voltage profile and reliability are poor. In this paper, HVDS is unveiled with smallcapacity distribution transformers. A simple load flow technique is used for solving distribution networks before and after implementation of HVDS. The advantages of implementing HVDS against LVDS system are discussed.

Background: India is a significant contributor to the world′s total burden of deafness. Out of all causes, almost 50% of the causes of decreased hearing are preventable. With the launch of the National Programme for Prevention and Control of Deafness, the need for an effective information, education and communication (IEC) campaign was felt. There is negligible information available about the status of awareness levels of the community about the various aspects of hearing loss. We carried out this research with the objective of getting to know the existing awareness related to hearing loss in the community to generate an evidence base for formulating various messages to be incorporated in IEC materials for dissemination in the community. We also asked the participants about their suggestions for the various information resources so that an IEC campaign could be designed accordingly. Materials and Methods: We carried out 10 focus group discussions among various groups of population and analyzed the discussion. Results: A descriptive analysis of the observations regarding the awareness about deafness in the community and prevalent myths and suggested information resources is presented. Conclusion: We highlight the lacunae in the existing awareness of various causes of deafness and the preventive measures that could be taken to prevent hearing loss. The evidence generated was used to formulate relevant messages for the various target groups, which were then incorporated in development of the IEC materials for the dissemination in the community.

Abstract Background At least two million Canadian children meet established criteria for weight management. Due to the adverse health consequences of obesity, most pediatric weight management research has examined the efficacy and effectiveness of interventions to improve lifestyle behaviors, reduce co-morbidities, and enable weight management. However, little information is available on families’ decisions to initiate, continue, and terminate weight management care. This is an important knowledge gap since a substantial number of families fail to initiate care after being referred for weight management while many families who initiate care discontinue it after a brief period of time. This research aims to understand the interplay between individual, family, environmental, and systemic factors that influence families’ decisions regarding the management of pediatric obesity. Methods/Design Individual interviews will be conducted with children and youth with obesity (n = 100) and their parents (n = 100) for a total number of 200 interviews with 100 families. Families will be recruited from four Canadian multi-disciplinary pediatric weight management centers in Vancouver, Edmonton, Hamilton, and Montreal. Participants will be purposefully-sampled into the following groups: (i) Non-Initiators (5 families/site): referred for weight management within the past 6 months and did not follow-up the referral; (ii) Initiators (10 families/site): referred for weight management within the past 6 months and did follow-up the referral with at least one clinic appointment; and (iii) Continuers (10 families/site): participated in a formal weight management intervention within the past 12 months and did continue with follow-up care for at least 6 months. Interviews will be digitally recorded and analyzed using an ecological framework, which will enable a multi-level evaluation of proximal and distal factors that underlie families’ decisions regarding initiation, continuation, and termination of care. Demographic and anthropometric/clinical data will also be collected. Discussion A better understanding of family involvement in pediatric weight management care will help to improve existing health services in this area. Study data will be used in future research to develop a validated survey that clinicians working in pediatric obesity management can use to understand and enhance their own health services delivery.

Abstract Background Bariatric surgery is the most effective current treatment for severe obesity. Capacity to perform surgery within Canada’s public health system is limited and potential candidates face protracted wait times. A better understanding of the gaps between demand for surgery and the capacity to provide it is required. The purpose of this study was to quantify and characterize the bariatric surgery-eligible population in Canada in comparison to surgery-ineligible subjects and surgical recipients. Methods Data from adult (age > 20) respondents of the 2007–09 nationally representative Canadian Health Measures Survey (CHMS) were analyzed to estimate the prevalence and characteristics of the surgery-eligible and ineligible populations. Federally mandated administrative healthcare data (2007–08) were used to characterize surgical recipients. Results In 2007–09, an estimated 1.5 million obese Canadian adults met eligibility criteria for bariatric surgery. 19.2 million were surgery-ineligible (3.4 million obese and 15.8 million non-obese). Surgery-eligible Canadians had a mean BMI of 40.1 kg/m2 (95% CI 39.3 to 40.9 kg/m2) and, compared to the surgery-ineligible obese population, were more likely to be female (62 vs. 44%), 40–59 years old (55 vs. 48%), less educated (43 vs. 35%), in the lowest socioeconomic tertile (41 vs. 34%), and inactive (73 vs. 59%). Self-rated mental health and quality of life were lower and comorbidity was higher in surgery-eligible respondents compared with the ineligible populations. The annual proportion of Canadians eligible for surgery that actually underwent a publicly funded bariatric surgery between 2007–09 was 0.1%. Surgical recipients (n = 847) had a mean age of 43.6 years (SD 11.1) and 82% were female. With the exception of type 2 diabetes, obesity-related comorbidity prevalence was much lower in surgical recipients compared to those eligible for surgery. Conclusions The proportion of bariatric surgery-eligible Canadians that undergo publicly funded bariatric surgery is very low. There are notable differences in sociodemographic profiles and prevalence of comorbidities between surgery-eligible subjects and surgical recipients.

Abstract Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend group-based sessions on a weekly basis. Anthropometry, cardiometabolic risk factors, lifestyle behaviours, and psychosocial health of children and parents are assessed at pre-intervention, post-intervention, 6-, and 12-months follow-up. Discussion This study is designed to extend findings from earlier efficacy studies and provide data on the effect of a CBT-based PAC intervention for managing pediatric obesity in a real-world, outpatient clinical setting. Trial Registration ClinicalTrials.gov identifier: NCT01267097

Abstract Background Protracted, multi-year wait times exist for bariatric care in Canada. Our objective was to examine wait-listed patients’ health status and perceptions regarding the consequences of prolonged wait times using a cross-sectional study design nested within a prospective cohort. Methods 150 consecutive consenting subjects wait-listed for multi-disciplinary bariatric assessment in a population-based medical/surgical bariatric program were surveyed. Health status was measured using a visual analogue scale (VAS). A Waiting List Impact Questionnaire (WLIQ) examined employment, physical stress, social support, frustration, quality of life, and satisfaction with care. Multivariable linear regression analysis adjusted for age, sex and BMI identified independent predictors of lower VAS scores. Results 136 (91%) subjects were women, mean age was 43 years (SD 9), mean BMI was 49.4 (SD 8.3) kg/m2 and average time wait-listed was 64 days (SD 76). The mean VAS score was 53/100 (SD 22). According to the WLIQ, 47% of subjects agreed/strongly agreed that waiting affected their quality of life, 65% described wait times as ‘concerning’ and 81% as ‘frustrating’. 86% reported worsening of physical symptoms over time. Nevertheless, only 31% were dissatisfied/very dissatisfied with their overall medical care. Independent predictors of lower VAS scores were higher BMI (beta coefficient 0.42; p = 0.03), unemployment (13.7; p = 0.01) and depression (10.3; p = 0.003). Conclusions Patients wait-listed for bariatric care self-reported very impaired health status and other adverse consequences, attributing these to protracted waits. These data may help benchmark the level of health impairment in this population, understand the physical and mental toll of waiting, and assist with wait list management. Trial registration Clinicaltrials.gov NCT00850356

Abstract Background Targeted interventions (TIs) have been a major strategy for HIV prevention in India. We evaluated the impact of TIs on HIV prevalence in high HIV prevalence southern states (Tamil Nadu, Karnataka, Andhra Pradesh and Maharashtra). Methods A quasi-experimental approach was used to retrospectively compare changes in HIV prevalence according to the intensity of targeted intervention implementation. Condom gap (number of condoms required minus condoms supplied by TIs) was used as an indicator of TI intensity. Annual average number of commercial sex acts per female sex worker (FSW) reported in Behavioral Surveillance Survey was multiplied by the estimated number of FSWs in each district to calculate annual requirement of condoms in the district. Data of condoms supplied by TIs from 1995 to 2008 was obtained from program records. Districts in each state were ranked into quartiles based on the TI intensity. Primary data of HIV Sentinel Surveillance was analyzed to calculate HIV prevalence reductions in each successive year taking 2001 as reference year according to the quartiles of TI intensity districts using generalized linear model with logit link and binomial distribution after adjusting for age, education, and place of residence (urban or rural). Results In the high HIV prevalence southern states, the number of TI projects for FSWs increased from 5 to 310 between 1995 and 2008. In high TI intensity quartile districts (n = 30), 186 condoms per FSW/year were distributed through TIs as compared to 45 condoms/FSW/year in the low TI intensity districts (n = 29). Behavioral surveillance indicated significant rise in condom use from 2001 to 2009. Among FSWs consistent condom use with last paying clients increased from 58.6% to 83.7% (p < 0.001), and among men of reproductive age, the condom use during sex with non-regular partner increased from 51.7% to 68.6% (p < 0.001). A significant decline in HIV and syphilis prevalence has occurred in high prevalence southern states among FSWs and young antenatal women. Among young (15-24 years) antenatal clinic attendees significant decline was observed in HIV prevalence from 2001 to 2008 (OR = 0.42, 95% CI 0.28-0.62) in high TI intensity districts whereas in low TI intensity districts the change was not significant (OR = 1.01, 95% CI 0.67-1.5). Conclusion Targeted interventions are associated with HIV prevalence decline.

Abstract Background Extreme obesity affects nearly 8% of Canadians, and is debilitating, costly and ultimately lethal. Bariatric surgery is currently the most effective treatment available; is associated with reductions in morbidity/mortality, improvements in quality of life; and appears cost-effective. However, current demand for surgery in Canada outstrips capacity by at least 1000-fold, causing exponential increases in already protracted, multi-year wait-times. The objectives and hypotheses of this study were as follows: 1. To serially assess the clinical, economic and humanistic outcomes in patients wait-listed for bariatric care over a 2-year period. We hypothesize deterioration in these outcomes over time; 2. To determine the clinical effectiveness and changes in quality of life associated with modern bariatric procedures compared with medically treated and wait-listed controls over 2 years. We hypothesize that surgery will markedly reduce weight, decrease the need for unplanned medical care, and increase quality of life; 3. To conduct a 3-year (1 year retrospective and 2 year prospective) economic assessment of bariatric surgery compared to medical and wait-listed controls from the societal, public payor, and health-care payor perspectives. We hypothesize that lower indirect, out of pocket and productivity costs will offset increased direct health-care costs resulting in lower total costs for bariatric surgery. Methods/design Population-based prospective cohort study of 500 consecutive, consenting adults, including 150 surgically treated patients, 200 medically treated patients and 150 wait-listed patients. Subjects will be enrolled from the Edmonton Weight Wise Regional Obesity Program (Edmonton, Alberta, Canada), with prospective bi-annual follow-up for 2 years. Mixed methods data collection, linking primary data to provincial administrative databases will be employed. Major outcomes include generic, obesity-specific and preference-based quality of life assessment, patient satisfaction, patient utilities, anthropometric indices, cardiovascular risk factors, health care utilization and direct and indirect costs. Discussion The results will identify the spectrum of potential risks associated with protracted wait times for bariatric care and will quantify the economic, humanistic and clinical impact of surgery from the Canadian perspective. Such information is urgently needed by health-service providers and policy makers to better allocate use of finite resources. Furthermore, our findings should be widely-applicable to other publically-funded jurisdictions providing similar care to the extremely obese. Trial Registration Clinicaltrials.gov NCT00850356

Abstract Background Diminished expression or activity of prostate apoptosis response protein 4 (Par-4) has been demonstrated in a number of cancers, although reports on Par-4 expression during colon cancer progression are lacking. An understanding of the molecular events in conjunction with the genetic networks affected by Par-4 is warranted. Results Colon cancer specimens derived from patients have significantly diminished expression of Par-4 mRNA relative to paired normal colon. Hence, the functional consequences of reintroducing Par-4 into HT29 colon cancer cells were assessed. Overexpression augmented the interaction of Par-4 with NFκB in the cytosol but not nucleus, and facilitated apoptosis in the presence of 5-fluorouracil (5-FU). Analogous findings were obtained when AKT1 pro-survival signaling was inhibited. Transcriptome profiling identified ~700 genes differentially regulated by Par-4 overexpression in HT29 cells. Nearly all Par-4-regulated genes were shown by promoter analysis to contain cis-binding sequences for NFκB, and meta-analysis of patient expression data revealed that one-third of these genes exist as a recurrent co-regulated network in colon cancer specimens. Sets of genes involved in programmed cell death, cell cycle regulation and interestingly the microRNA pathway were found overrepresented in the network. Noteworthy, Par-4 overexpression decreased NFκB occupancy at the promoter of one particular network gene DROSHA, encoding a microRNA processing enzyme. The resulting down-regulation of DROSHA was associated with expression changes in a cohort of microRNAs. Many of these microRNAs are predicted to target mRNAs encoding proteins with apoptosis-related functions. Western and functional analyses were employed to validate several predictions. For instance, miR-34a up-regulation corresponded with a down-regulation of BCL2 protein. Treating Par-4-overexpressing HT29 cells with a miR-34a antagomir functionally reversed both BCL2 down-regulation and apoptosis by 5-FU. Conversely, bypassing Par-4 overexpression by direct knockdown of DROSHA expression in native HT29 cells increased miR-34a expression and 5-FU sensitivity. Conclusion Our findings suggest that the initiation of apoptotic sensitivity in colon cancer cells can be mediated by Par-4 binding to NFκB in the cytoplasm with consequential changes in the expression of microRNA pathway components.

Abstract Background Obesity, type 2 diabetes mellitus (T2D) and unhealthy blood lipid profile are strongly associated with the risk of developing cardiovascular disease (CVD). We examined whether blood lipid changes with short term administration of the weight lowering drug, sibutramine and lifestyle modification in obese and overweight high-risk patients was associated with T2D status at screening. Methods The Sibutramine Cardiovascular OUTcomes (SCOUT) trial included obese and overweight patients at increased risk of cardiovascular events. All patients received guidance on diet and exercise plus once-daily 10 mg sibutramine during the 6-week, single blind lead-in period. Multivariable regression models were used to investigate factors associated with changes in lipid levels during the first four weeks of treatment. Results A total of 10 742 patients received at least one dose of sibutramine during the 6-week lead-in period of SCOUT. After four weeks, patients experienced mean reductions in low density lipoprotein (LDL-C) 0.19 mmol/L, high density lipoprotein (HDL-C) 0.019 mmol/L, very low density lipoprotein (VLDL-C) 0.08 mmol/L, total cholesterol (TC) 0.31 mmol/L and triglycerides 0.24 mmol/L (p < 0.0001 for each). Four week changes in LDL-C, HDL-C and total cholesterol for patients without vs. with T2D were: LDL-C:-0.25 mmol/L vs. -0.18 mmol/L, P = 0.0004; HDL-C: -0.03 mmol/L vs. -0.02 mmol/L, P = 0.0014; total cholesterol: -0.37 mmol/l vs. -0.29 mmol/l, P = 0.0009. Multivariable regression analysis showed that similar decreases in body mass index (BMI) affected lipid changes differently according to diabetes status. A 1 kg/m2 decrease in BMI in patients with T2D was associated with -0.09 mmol/L in LDL-C (P < 0.0001) and -0.01 mmol/L in HDL-C (P = 0.0001) but larger changes of -0.16 mmol/L LDL-C and -0.03 mmol/L in HDL-C (P < 0.0001 for both) in patients without T2D. Conclusion Short term weight management with sibutramine therapy in obese or overweight high-risk patients induced significant mean reductions for all lipids. Those without T2D benefited most. Patients with hyperlipidaemia and the less obese patients also had greater falls in LDL-C and TC during weight loss. The trial is registered at ClinicalTrial.gov number: NCT00234832.

Abstract Background and aims Elevated levels of serum uric acid are associated with an increased risk of cardiovascular morbidity and mortality. The response of uric acid to weight loss therapy (lifestyle plus sibutramine) in an overweight and obese cardiovascular high risk population was studied. Methods and results Data from a four week single-blind lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) study were analyzed. 2584 patients (24%) had diabetes mellitus (DM) only, 1748 (16%) had cardiovascular disease (CVD) only and 6397 (60%) had both DM + CVD. Uric acid concentrations (mean ± standard deviation) at screening were significantly higher among patients with CVD compared to patients without CVD (p < 0.0001): 369 ± 86 μmol/L, 374 ± 98 μmol/L and 342 ± 87 μmol/L in CVD only, CVD+DM and DM only groups, respectively. During treatment uric acid decreased significantly more in patients without DM (p < 0.0001): -15.0 μmol/L (95% confidence interval -17.7;-12.4), -4.6 μmol/L (-6.2;-3.0), and -6.6 μmol/L (-8.7;-4.5) in CVD only, CVD+DM, and DM only groups, respectively. In patients who failed to lose weight, sibutramine induced lower uric acid levels, but greater weight loss and diabetes were associated with smaller falls in blood uric acid levels; decreasing fasting and urinary glucose concentrations in diabetes were associated with increases in uric acid levels. Conclusion A four week daily intake of sibutramine and life style changes was associated with significant reductions in mean uric acid levels. Changes in renal glucose load in diabetes seem to counteract a potential uricosuric effect of sibutramine. Trial Registration The trial is registered at ClinicalTrial.gov number: NCT00234832.

Abstract Background Hormones are signaling molecules that play vital roles in various life processes, like growth and differentiation, physiology, and reproduction. These molecules are mostly secreted by endocrine glands, and transported to target organs through the bloodstream. Deficient, or excessive, levels of hormones are associated with several diseases such as cancer, osteoporosis, diabetes etc. Thus, it is important to collect and compile information about hormones and their receptors. Description This manuscript describes a database called Hmrbase which has been developed for managing information about hormones and their receptors. It is a highly curated database for which information has been collected from the literature and the public databases. The current version of Hmrbase contains comprehensive information about ~2000 hormones, e.g., about their function, source organism, receptors, mature sequences, structures etc. Hmrbase also contains information about ~3000 hormone receptors, in terms of amino acid sequences, subcellular localizations, ligands, and post-translational modifications etc. One of the major features of this database is that it provides data about ~4100 hormone-receptor pairs. A number of online tools have been integrated into the database, to provide the facilities like keyword search, structure-based search, mapping of a given peptide(s) on the hormone/receptor sequence, sequence similarity search. This database also provides a number of external links to other resources/databases in order to help in the retrieving of further related information. Conclusion Owing to the high impact of endocrine research in the biomedical sciences, the Hmrbase could become a leading data portal for researchers. The salient features of Hmrbase are hormone-receptor pair-related information, mapping of peptide stretches on the protein sequences of hormones and receptors, Pfam domain annotations, categorical browsing options, online data submission, DrugPedia linkage etc. Hmrbase is available online for public from http://crdd.osdd.net/raghava/hmrbase/.

Abstract Background Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic) speaking populations originated in India or derive from a relatively recent migration from further East. Results Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1), is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari) of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between genetic variation and geography, rather than between genes and languages. Conclusion Our high-resolution phylogeographic study, involving diverse linguistic groups in India, suggests that the high frequency of mtDNA haplogroup R7 among Munda speaking populations of India can be explained best by gene flow from linguistically different populations of Indian subcontinent. The conclusion is based on the observation that among Indo-Europeans, and particularly in Dravidians, the haplogroup is, despite its lower frequency, phylogenetically more divergent, while among the Munda speakers only one sub-clade of R7, i.e. R7a1, can be observed. It is noteworthy that though R7 is autochthonous to India, and arises from the root of hg R, its distribution and phylogeography in India is not uniform. This suggests the more ancient establishment of an autochthonous matrilineal genetic structure, and that isolation in the Pleistocene, lineage loss through drift, and endogamy of prehistoric and historic groups have greatly inhibited genetic homogenization and geographical uniformity.

Abstract Background Obesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss current epidemiological data on the prevalence of obesity in European countries. Methods We identified relevant published studies by means of a MEDLINE search (1990–2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each country's overall population. Results In Europe, the prevalence of obesity (body mass index ≥ 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe. Conclusion In Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.

Abstract Background The diverse physiological and pathological role of nitric oxide in innate immune defenses against many intra and extracellular pathogens, have led to the development of various methods for determining nitric oxide (NO) synthesis. NO metabolites, nitrite (NO2-) and nitrate (NO3-) are produced by the action of an inducible Anopheles culicifacies NO synthase (AcNOS) in mosquito mid-guts and may be central to anti-parasitic arsenal of these mosquitoes. Method While exploring a plausible mechanism of refractoriness based on nitric oxide synthase physiology among the sibling species of An. culicifacies, a sensitive, specific and cost effective high performance liquid chromatography (HPLC) method was developed, which is not influenced by the presence of biogenic amines, for the determination of NO2- and NO3- from mosquito mid-guts and haemolymph. Results This method is based on extraction, efficiency, assay reproducibility and contaminant minimization. It entails de-proteinization by centrifugal ultra filtration through ultracel 3 K filter and analysis by high performance anion exchange liquid chromatography (Sphereclone, 5 μ SAX column) with UV detection at 214 nm. The lower detection limit of the assay procedure is 50 pmoles in all midgut and haemolymph samples. Retention times for NO2- and NO3- in standards and in mid-gut samples were 3.42 and 4.53 min. respectively. Assay linearity for standards ranged between 50 nM and 1 mM. Recoveries of NO2- and NO3- from spiked samples (1–100 μM) and from the extracted standards (1–100 μM) were calculated to be 100%. Intra-assay and inter assay variations and relative standard deviations (RSDs) for NO2- and NO3- in spiked and un-spiked midgut samples were 5.7% or less. Increased levels NO2- and NO3- in midguts and haemolymph of An. culicifacies sibling species B in comparison to species A reflect towards a mechanism of refractoriness based on AcNOS physiology. Conclusion HPLC is a sensitive and accurate technique for identification and quantifying pmole levels of NO metabolites in mosquito midguts and haemolymph samples that can be useful for clinical investigations of NO biochemistry, physiology and pharmacology in various biological samples.

Abstract Background Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. Methods We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. Results UCP1 A-3826G was associated with AIRg in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). Conclusion This study suggests a functional variant of UCP1 contributes to the variance of AIRg in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets.

The diagnosis, treatment, and management of dementia provide significant challenges due to its chronic cognitive impairment. The complexity of this condition is further highlighted by the impact of gene-environment interactions. A recent strategy combines advanced genomics and precision medicine methods to explore the complex genetic foundations of dementia. Utilizing the most recent research in the field of neurogenetics, the importance of precise genetic data in explaining the variation seen in dementia patients can be investigated. Gene-environment interactions are important because they influence genetic susceptibilities and aid in the development and progression of dementia. Modified to each patient's genetic profile, precision medicine has the potential to detect groups at risk and make previously unheard-of predictions about the course of diseases. Precision medicine techniques have the potential to completely transform treatment and diagnosis methods. Targeted medications that target genetic abnormalities will probably appear, providing the possibility for more efficient and customized medical interventions. Investigating the relationship between genes and the environment may lead to preventive measures that would enable people to change their surroundings and minimize the risk of dementia, leading to the improved lifestyle of affected people. This paper provides a comprehensive overview of the genomic insights into dementia, emphasizing the pivotal role of precision medicine, and gene-environment interactions.

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic premalignant lesions frequently detected incidentally. Choosing between surgery and surveillance for IPMNs is rooted in uncertainty. We characterized patient preferences in IPMN management, and examined associations with patients' uncertainty profiles (risk perception, risk attitude, and uncertainty tolerance)., Methods: We conducted a cross-sectional survey drawn from a national opt-in panel. We simulated an encounter following an incidental computed tomography scan finding of an IPMN with a 5% cancer risk. We elicited participants' preferred treatment (surgery versus surveillance). Participant cancer risk perception, risk attitude (risk seeking versus risk averse), and uncertainty tolerance (comfort with the unknown) were determined using validated measures. Multivariate regression models assessed for independent predictors of treatment preference and risk perception., Results: The sample included 520 participants, ages 40-70, racially representative of the US population. Participants preferred surveillance (n = 331, 64%) over surgery (n = 189, 36%). Patients were significantly more likely to prefer surgery as their cancer risk perception increased (absolute difference = 12% from 1.0 standard deviation below to 1.0 standard deviation above the mean, 95% CI 3.5-20.2). Treatment preference was not significantly associated with risk attitude (P = 0.068) or uncertainty tolerance (P = 0.755). However, initial cancer risk perception was significantly associated with both uncertainty tolerance (P = 0.013) and baseline cancer anxiety (risk perception 16.4% versus 65%, not worried at all versus extremely worried, P < 0.001)., Conclusions: Patient preference varies widely for IPMN and is significantly associated with cancer risk perception, which is, in turn, significantly associated with uncertainty tolerance and cancer anxiety. These findings argue for the preference-sensitive nature of IPMN treatment decisions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aging process is associated with the development of a wide range of degenerative disorders in mammals. These diseases are characterized by a progressive decline in function at multiple levels, including the molecular, cellular, tissue, and organismal. Furthermore, it is responsible for various healthcare costs in developing and developed countries. Sarcopenia is the deterioration in the quality and functionality of muscles, which is extremely concerning as it manages many functions in the human body. This article reviews the molecular crosstalk involved in sarcopenia and the specific roles of many mediator molecules in establishing cross-talk between muscles, bone, and fatty tissues, eventually leading to sarcopenia. Besides, the involvement of various etiological factors, such as neurology, endocrinology, lifestyle, etc., makes it exceedingly difficult for clinicians to develop a coherent hypothesis that may lead to the well-organized management system required to battle this debilitating disease. The several hallmarks contributing to the progression of the disease is a vital question that needs to be addressed to ensure an efficient treatment for sarcopenia patients. Also, the intricate molecular mechanism involved in developing this disease requires more studies. The direct relationship of cellular senescence with aging is one of the pivotal issues contributing to disease pathophysiology. Some patented treatment strategies have been discussed, including drugs undergoing clinical trials and emerging options like miRNA and protein-enclosed extracellular vesicles. A clear understanding of the secretome, including the signaling pathways involved between muscles, bone, and fatty tissues, is extremely beneficial for developing novel therapeutics for curing sarcopenia.

Quercetin (QC), a naturally occurring bioflavonoid found in various fruits and vegetables, possesses many potential health benefits, primarily attributed to its robust antioxidant properties. The generation of oxidative stress in bone cells is a key modulator of their physiological behavior. Moreover, oxidative stress status influences the pathophysiology of mineralized tissues. Increasing scientific evidence demonstrates that manipulating the redox balance in bone cells might be an effective technique for developing bone disease therapies. The QC antioxidant abilities in skeletal muscle significantly enhance muscle regeneration and reduce muscle atrophy. In addition, QC has been shown to have protective effects against oxidative stress, inflammation, apoptosis, and matrix degradation in tendons, helping to maintain the structural integrity and functionality of tendons. Thus, the antioxidant properties of QC might be crucial for addressing age-related musculoskeletal disorders like osteoporosis, sarcopenia, and tendon-related inflammatory conditions. Understanding how QC influences redox signaling pathways involved in musculoskeletal disorders, including their effect on bone, muscle, and tendon differentiation, might provide insights into the diverse advantages of QC in promoting tissue regeneration and preventing cellular damage. Therefore, this study reviewed the intricate relationship among oxidative stress, inflammation, and tissue repair, affected by the antioxidative abilities of QC, in age-related musculoskeletal tissues to improve the overall health of bones, muscles, and tendons of the skeletal system. Also, reviewing the ongoing clinical trials of QC for musculoskeletal systems is encouraging. Given the positive effect of QC on musculoskeletal health, further scientific investigations and controlled human intervention studies are necessary to explore the therapeutic potential to its optimum strength.

Periodontitis, a prevalent chronic inflammatory condition affecting the supporting structures of teeth, is closely associated with oxidative stress, characterized by an imbalance between reactive oxygen species generation and antioxidant defense mechanisms. Antioxidants have garnered significant attention as potential therapeutic agents in periodontal management due to their ability to counteract oxidative damage and inflammation. This brief review provides an overview of the role of antioxidants in periodontitis, highlighting recent developments. Key topics covered include the mechanisms of action of antioxidants, recent preclinical and clinical studies evaluating their efficacy, challenges, and future directions in antioxidant-based periodontal therapy. Recent advancements in antioxidant research offer promising avenues for improving periodontal treatment outcomes and patient care., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Successful kidney transplant corrects mineral and bone disorderto a large extent; however, disorders can persistin up to 80% ofrecipients.We describe a case of persistent hyperparathyroidism with graft dysfunction and metastatic calcification in graft biopsy. A 48-yearold renal transplant recipient developed graft dysfunction 3 weeks after kidney transplant. During pretransplant workup, the recipient was found to have severe secondary hyperparathyroidism (intact parathyroid hormone level of 2000 pg/mL), which was managed and well controlled before transplant. Graft dysfunction was evaluated using algorithmic approach. Prerenal causes, tacrolimus toxicity, and infections were ruled out. Graft biopsy revealed several foci of tubular and parenchyma calcific deposits (microcalcinosis) with tubular injury. The patient was restarted on medical management of hyperparathyroidism, and he showed improvement over 6 weeks, along with creatinine level returning to nadir value. Vascular and graft calcification is an independent predictor of long-term graftfunction and overall mortality. This report describes the challenges that we faced in diagnosis and management of persistent hyperparathyroidism, as no randomized controlled trials and guidelines are available.

Objective: The association between eating disorders (EDs) and harmful substance use (substance use that causes psychosocial impairment) is well recognized in the literature, and military veterans may be at heightened risk for both issues due to deployment-related stressors. However, little is known about which ED-related symptoms are associated with harmful substance use in veterans, and whether gender plays a differential role in this relationship. Our aims were to: (1) examine gender differences in ED-related symptoms; and (2) examine whether ED-related symptoms differentially predict harmful substance use in US veteran men and women who had recently separated from service., Method: This study was based on a nationally representative four-wave longitudinal sample of post-9/11 veterans (N = 835; 61.2% female). Longitudinal mixed modeling was used to test whether specific ED-related behaviors at baseline predicted harmful substance use at follow-ups., Results: We replicated gendered patterns of ED-related symptoms observed in civilian populations, wherein men had higher weight-and-body-related concerns (including excessive exercise and muscle building) and negative attitude toward obesity, and women had higher bulimic and restricting symptoms. For women, alcohol, drug, and marijuana problems were predicted by higher bulimic symptoms, whereas for men, these problems were predicted by higher restricting symptoms., Conclusion: Gender played a differential role in the relationship between EDs and harmful substance use. Bulimic symptoms were the most robust predictor for harmful substance use among veteran women, whereas restricting was the most robust predictor for harmful substance use among veteran men., Public Significance: The current study found that veteran women had higher bulimic symptoms (characterized by binge eating and purging) and restricting than veteran men. In women, bulimic symptoms predicted future harmful use of alcohol, marijuana, and other drugs. In contrast, veteran men had higher weight-and-body-related concerns (characterized by excessive exercise and muscle building) than veteran women. In men, restricting symptoms predicted future harmful use of alcohol, marijuana, and other drugs., (© 2024 Wiley Periodicals LLC.)

Background: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs., Results: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice., Conclusion: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications., (© 2024. The Author(s).)

Objective: We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs)., Summary Background Data: The complexity of IPMN management provides an opportunity to align treatment with individual preference., Methods: We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression., Results: The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively)., Conclusions: Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Amid growing concerns about diminishing river sand resources and escalating environmental apprehensions related to toxic landfill waste, this study explores the potential of Toxic Foundry Sand (TFS) as a substitute for Standard Fine Aggregate (SFA) in concrete production. The investigation into various TFS replacement ratios in M20 concrete focuses on their impact on workability and compressive strength. Although TFS exhibits properties similar to fine aggregate, making it a promising candidate for partial replacement, differences in bulk density and fineness modulus compared to river sand suggest that TFS should be utilized as a partial replacement only. The study proposes an optimal replacement ratio of 30 % TFS and 70 % SFA to achieve satisfactory compressive strength in M20 concrete. The workability of fresh concrete remains unaffected in both nominal and 70:30 mixes, ensuring ease of mixing on the job site. As an innovative aspect, the study includes testing the water exposed to TFS-infused concrete for portability. Prolonged exposure to water on TFS-infused concrete (70:30 mix) raises concerns, as certain parameters such as chloride and hardness exceed acceptable limits. Therefore, careful control and treatment of Toxic Foundry Sand Contact Water (TFSCW) are deemed crucial on job sites to address potential water quality issues and ensure overall environmental safety., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The development of efficient therapies for Alzheimer''s disease is essential since it is a serious public health problem. This investigation sought to ascertain any potential synergistic benefits of treating Alzheimer's disease with IRL-1620 monotherapy in addition to Donepezil. Additionally, the effect of IRL-1620 was evaluated using different doses (5 μg/kg,7 μg/kg, and 9 μg/kg). The study further assessed neurobehavioral, biochemical, molecular, and histopathological parameters to evaluate the efficacy of both IRL1620 by its own and in association with Donepezil. Fifty-eight adult male Wistar rats were allocated to eight experimental groups. A dose-ranging study of IRL-1620 was conducted using different doses administered via intravenous injection. Alzheimer's disease was induced by Aβ administration, and treatment arms included disease Control (Sham), Donepezil monotherapy, and combination treatment with IRL-1620 5 μg/kg (Dose selected from the dose-ranging study). The treatment using IRL-1620 (9 μg/kg) intravenously and Donepezil (1 mg/kg orally) both on its own and in addition substantially enhanced memory in comparison with the control group (p < 0.05). Dose of IRL-1620 (9 μg/kg) intravenously, escape latency decreased and the time spent in the target quadrant was considerably increased, and they further benefited from combination therapy. Moreover, IRL-1620 (9 μg/kg) intravenously and combination treatment reduced lipid peroxidation and acetylcholinesterase levels while increasing antioxidant enzyme levels. Immunohistochemistry and molecular analysis revealed enhanced expression of neurotrophic factors with combination treatment. The combination of IRL-1620 and Donepezil showed significant improvements in memory and neurobehavioral parameters (p < 0.05). Alzheimer's disease in male Wistar rats. These results indicate to the probable therapeutic advantages of IRL-1620 and Donepezil in the management of Alzheimer's disease. The combination treatment exhibited enhanced effects compared to monotherapy, highlighting its potential promising therapeutic approach. Additional research is required to understand the mechanisms behind these synergistic benefits and to establish the ideal dosage and duration of therapy for therapeutic applications., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)