Structural and kinetic studies of bifunctional and monofunctional proline catabolic enzymes

Title from PDF of title page (University of Missouri--Columbia, viewed on December 4, 2015).PutAs, Proline dehydrogenase and P5C dehydrogenase are involved in the oxidation of proline to glutamate. Mutations in proline dehydrogenase and P5C dehydrogenase cause a disease condition known as hyperprolinemia. In this work I have solved the crystal structure of bifunctional PutA and P5C dehydrogenase. The structure of P5C dehydrogenase sheds light on the structural basis of hyperprolinemia. I have also used kinetic and thermodynamic methods to understand the molecular mechanism of hyperprolinemia

Prevalence and knowledge of hypertension among students of medical college of central Uttar Pradesh, India

Background: Hypertension is one of the biggest health challenges, which is continuously increasing among young adults, especially students. The aim of the present study was to find out the prevalence, associated factors and knowledge of hypertension among undergraduate students of a medical college of a rural area in central Uttar Pradesh, India. Methodology:  A cross-sectional study was conducted in one of the medical college of central Uttar Pradesh, India. Data were collected on socio-demographic and behavioral factors, and anthropometric assessments were carried out using standard equipment and procedures. Results: The present research involved 147 undergraduate medical students with a mean age of 21.9±2.2 years. Knowledge about hypertension was poor, average and good among19.7% (n=29), 76.8% (n=113) and 3.4% (n=5) students, respectively. Mean systolic blood pressure (mean SBP) was 127.07 ± 10.109 mm of Hg with a range 110 to 154mm of Hg, and mean diastolic blood pressure (mean DBP) was 80.5 ± 6.587 mm Hg with a range 68 to 94 mm of Hg. Conclusions: Smoking, alcoholism, non-vegetarian diet, body weight over 60 kgs and waist-hip ratio over 0.9 were recognized as risk factors of hypertension. Hence it needs a powerful surveillance program to find the exact problem

Prevalence of complications of Type 2 Diabetes Mellitus and its association with different risk factors in Urban Etawah, Uttar Pradesh

Background- India is experiencing a rapid health transition, with large and rising burdens of chronic diseases, which were estimated to account for 53% of all deaths in 2005. Earlier estimates projected that the number of deaths attributable to chronic diseases would rise from 3·78 million in 1990 (40·4% of all deaths) to 7·63 million in 2020 (66·7% of all deaths). Aims and Objectives- To find out the prevalence of Complications of Type 2 Diabetes Mellitus and its association with different risk factors in Urban Etawah (U.P.) including tobacco, alcohol, fatty meals and physical activity. Material and Methods- The present study is a community-based study performed among 400 participants using cluster sampling technique in the field practice area of Urban health training centre, Department of Community Medicine, UPUMS, Saifai, Etawah. The participants were interviewed using a pre-tested questionnaire using Diabetes Complication Index.  Results- Among the diabetics, the prevalence of coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular accidents (CVA), cataract, neuropathy and foot problems were 24%, 24%, 7%, 15.4%, 38%, 26% and 2% respectively. A statistically significant association was seen with fatty meals and complications. Conclusion - All the diabetic complications observed need to be addressed in prevention and control strategies in the study area. Heath screening camps will be organized for the people for awareness

Prevalence of Diabetic Peripheral Neuropathy among Type 2 Diabetes Mellitus patients and its associated risk factors

Background: Diabetic peripheral neuropathy (DPN) is a common and one of the severe complications of diabetes mellitus. It affects almost half the diabetic population and worsens quality of life of the patient. The present study was aimed to determine the prevalence of peripheral neuropathy and associated risk factors. Aims and Objectives: To assess the Prevalence of Diabetic Peripheral Neuropathy (DPN) among Type 2 DM patients and its associated risk factors. Material and Methods: A community based survey was conducted over a period of one and a half year. Cluster sampling technique was used to collect the study sample in urban Etawah. Study participants aged ? 30 years residing in urban Etawah with known history of Type 2 Diabetes Mellitus of ? 5 years were included in the study. Diabetic Peripheral Neuropathy (DPN) was diagnosed using 10 g monofilament test. Results: A total of 400 DM patients were enrolled in the study. Out of which 28% (n = 112) patients were diagnosed with DPN using Semmes-Weinstein (SW) 10-g monofilament test. Statistically significant association was also noted with Family history of DM, BMI, Systolic and Diastolic blood pressure, Family history of HTN and History of Smoking. Conclusion: The current study found a high prevalence of DPN (28%) and it was found to be significantly associated with advancing age, duration of diabetes and history of smoking

Impact of health education on knowledge and attitude of self-breast examination among female nursing students

Background: Breast cancer is the most common cancer among women and a leading cause of death worldwide, including in India. Breast cancer usually shows a slow development rate, and when it is recognized in the early stages, successful treatment results can be achieved. Breast self-examination is a screening option for young women. Health awareness programs on screening and early detection are the cornerstones for reducing the morbidity and mortality resulting from breast cancer. Objective: To assess the impact of health education on knowledge and attitude of self-breast examination among nursing students. Study Design: The present interventional study was conducted between September and October 2019. Setting: This study was done among 79 nursing students of a tertiary care hospital situated in a central district of Uttar Pradesh. Main Outcome Measures: The self-reported pre-designed and structured questionnaire was used. It included three sections: 1. Sociodemographic profile 2. Knowledge regarding self-breast examination (SBE) 3. Attitude regarding self-breast examination (SBE). Knowledge and attitude scores were calculated and divided into the poor, average, and good categories. Results: There were 87.3% of girls had prior knowledge of the self-breast examination, while 12.7% of girls were not aware of the self-breast examination. Post-intervention, there was a significant increase (p<0.05) in their knowledge about self-breast examination. Conclusion and Relevance: Planned teaching intervention had a significant impact on the knowledge and attitude of self-breast examination. The knowledge and attitude were poor at the early stages, but it had increased significantly after the health education intervention

Structure of the Proline Utilization A Proline Dehydrogenase Domain Inactivated by \u3ci\u3eN\u3c/i\u3e-propargylglycine Provides Insight into Conformational Changes Induced by Substrate Binding and Flavin Reduction

Proline utilization A (PutA) from Escherichia coli is a flavoprotein that has mutually exclusive roles as a transcriptional repressor of the put regulon and a membrane-associated enzyme that catalyzes the oxidation of proline to glutamate. Previous studies have shown that the binding of proline in the proline dehydrogenase (PRODH) active site and subsequent reduction of the FAD trigger global conformational changes that enhance PutA-membrane affinity. These events cause PutA to switch from its repressor to enzymatic role, but the mechanism by which this signal is propagated from the active site to the distal membrane-binding domain is largely unknown. Here, it is shown that N-propargylglycine irreversibly inactivates PutA by covalently linking the flavin N(5) atom to the ε-amino of Lys329. Furthermore, inactivation locks PutA into a conformation that may mimic the proline reduced, membrane-associated form. The 2.15 Å resolution structure of the inactivated PRODH domain suggests that the initial events involved in broadcasting the reduced flavin state to the distal membrane binding domain include major reorganization of the flavin ribityl chain, severe (35 degree) butterfly bending of the isoalloxazine ring, and disruption of an electrostatic network involving the flavin N(5), Arg431, and Asp370. The structure also provides information about conformational changes associated with substrate binding. This analysis suggests that the active site is incompletely assembled in the absence of the substrate, and the binding of proline draws together conserved residues in helix 8 and the β1-αl loop to complete the active site

Target and inhibitors for sars-cov-2 with its treatment opportunities: A theoretical study

The SARS-CoV-2 coronavirus is a new coronavirus that has sparked a worldwide pandemic with high rates of morbidity and mortality. The virus's rapid spread has highlighted the urgent need for potent treatments to stop COVID-19. A thorough analysis of these in silico methodologies is necessary to comprehend drug development for COVID-19 since computational methods have been essential in finding possible therapeutic targets and inhibitors for SARS-CoV-2. This article offers a thorough summary of the in-silico methods used to find prospective SARS-CoV-2 therapeutic targets and inhibitors. First, we discuss the mechanisms by which SARS-CoV-2 penetrates human cells as well as potential targets and receptors for the virus. The FDAapproved inhibitors and additional possible inhibitors that have been found through in silico investigations are then briefly discussed. Hydroxychloroquine, Remdesivir, Ribavirin, Tocilizumab, Galidesivir, Sofosbuvir, and Tenofovir are only a few of the inhibitors in this group. We also discuss the computational methods that have been applied to identify potential targets and inhibitors, including molecular dynamics simulations, virtual screening, docking investigations, and QSAR modelling. The findings of several in silico research on putative SARS-CoV-2 drugs and targets are also included in this study. This research includes analyses of the RNA-dependent RNA polymerase (RdRp), the spike glycoprotein (S), and proteases including the Mpro and 3-chymotrypsin-like protease. The results of several computational techniques used to research possible inhibitors, such as Hydroxychloroquine and Remdesivir, are also presented. Our analysis highlights the crucial part that computational techniques play in the hunt for SARS-CoV-2 drugs and offers suggestions for further study in this area. We also talk about the drawbacks of computational research and the requirement for further experimental verification of in silico findings. Overall, this evaluation is a crucial tool for scientists looking to develop COVID-19 treatments and find new drugs

Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer

Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions after a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes

Acute-on-Chronic Liver Failure (ACLF): The ‘Kyoto Consensus’-Steps From Asia

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the APASL ACLF Research Consortium (AARC) was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the \u27Golden Therapeutic Window\u27, the \u27transplant window\u27, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The \u27Kyoto APASL Consensus\u27 presented below carries the final recommendations along with the relevant background information and areas requiring future studies

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe