Characterization of an Acinetobacter baumannii Monofunctional Phosphomethylpyrimidine Kinase That Is Inhibited by Pyridoxal Phosphate.

Thiamin and its phosphate derivatives are ubiquitous molecules involved as essential cofactors in many cellular processes. The de novo biosynthesis of thiamin employs the parallel synthesis of 4-methyl-5-(2-hydroxyethyl)thiazole (THZ-P) and 4-amino-2-methyl-5(diphosphooxymethyl) pyrimidine (HMP) pyrophosphate (HMP-PP), which are coupled to generate thiamin phosphate. Most organisms that can biosynthesize thiamin employ a kinase (HMPK or ThiD) to generate HMP-PP. In nearly all cases, this enzyme is bifunctional and can also salvage free HMP, producing HMP-P, the monophosphate precursor of HMP-PP. Here we present high-resolution crystal structures of an HMPK from Acinetobacter baumannii (AbHMPK), both unliganded and with pyridoxal 5-phosphate (PLP) noncovalently bound. Despite the similarity between HMPK and pyridoxal kinase enzymes, our kinetics analysis indicates that AbHMPK accepts HMP exclusively as a substrate and cannot turn over pyridoxal, pyridoxamine, or pyridoxine nor does it display phosphatase activity. PLP does, however, act as a weak inhibitor of AbHMPK with an IC50 of 768 µM. Surprisingly, unlike other HMPKs, AbHMPK catalyzes only the phosphorylation of HMP and does not generate the diphosphate HMP-PP. This suggests that an additional kinase is present in A. baumannii, or an alternative mechanism is in operation to complete the biosynthesis of thiamin.

Competency based medical education as an accelerator to end tuberculosis (End TB) in India.

Tuberculosis is a major public health challenge in India and has been targeted for elimination. The National Tuberculosis Elimination Program (NTEP), in its all-previous forms has been one of the leading national health programs with the institutionalized engagement of medical colleges. This article outlines the mechanisms for medical college engagement in NTEP and discusses how the recent adoption of competency based medical education (CBME) for graduate medical education provides an opportunity for strengthening medical college participation in NTEP. The authors propose that for an accelerated progress towards 'End TB' in India, there is need for scaling up faculty development programs, focusing upon operational and implementation research, adopting a practical approach in designing curriculum for graduate medical teaching and creation of online repository of training material as well as the data bank of post-graduate theses, and other published and unpublished research work. Alongside, these efforts need to be supplemented by the professional associations of medical specialties and the governments through organizing annual national scientific and policy forum; and the capacity building of postgraduate students and faculty members in operational research, amongst others. The adoption of CBME has-arguably- created an opportunity for innovations at medical college level to support End TB. The learnings could also be utilized for enhanced engagement of medical colleges in other national health programs. India's experience on medical college engagement in tuberculosis elimination could serve as a 'good practice' for TB endemic countries in other parts of the world.

Metabolic syndrome burden, determinants and treatment status in an urban slum resettlement colony in Delhi, India.

BACKGROUND: Metabolic syndrome (MetS) in low-resource settings contributes to accentuated risk of cardiovascular disease, including stroke. The study objective was to estimate the prevalence, determinants and treatment status of MetS in an urban slum resettlement population in Delhi, India. METHODS: This study was conducted from February to May 2023. Multiphase sampling was conducted with 1910 individuals screened for abdominal obesity (AO), with 996 detected as having AO, of which, 400 were selected by simple random sampling and further evaluated for triglycerides (TGs), high-density lipoprotein (HDL) and fasting glucose levels. RESULTS: Among the 400 participants detected as having AO, 211 had evidence of MetS (52.75% [95% confidence interval 47.83 to 57.62]). The most prevalent combination of MetS clustering was for all five components (AO, diabetes mellitus [DM], hypertension [HTN], low HDL and high TGs; 14.69%), followed by AO, DM and HTN (12.32%). On adjusted analysis, the odds of having MetS was found to be independently associated with increasing age (≥40 y) but not sex. CONCLUSIONS: A high burden of MetS and suboptimal treatment status is prevalent in urban slum populations. Screening of individuals with AO, especially in those >40 y of age, can be an effective programmatic strategy for early diagnosis and management of MetS and its underlying components.

How can TB Mukt Panchayat initiative contribute towards ending tuberculosis in India?

Community Engagement (CE) for disease control and health has been tested for a long time across the globe for various health programmes. Realizing the need for true multisectoral action and CE and ownership for ending TB on an accelerated timeline, the Government of India launched a nationwide campaign for 'TB Mukt Panchayat' (meaning 'TB free village council' in Hindi language) on 24 March 2023, banking on the system of local self-governments in the country. Though it is an initiative with huge potential to contribute to India's efforts to end the TB epidemic, it is not without a few shortcomings. We critically analyse the TB Mukt Panchayat initiative and suggest a few recommendations for the way forward.

Unraveling the Relationship Between Osteoporosis, Treatment Modalities, and Oral Health: A Comprehensive Review.

This review delves into the intricate interplay between osteoporosis, its treatment approaches, and oral health. The examination underscores the substantial impact of osteoporosis, characterized by reduced bone density, on various oral health parameters such as periodontal health, tooth loss, and jawbone density. While pharmacological interventions, including bisphosphonates and hormone replacement therapy, play a crucial role in managing osteoporosis, they necessitate careful consideration, particularly about the risk of osteonecrosis of the jaw. A comprehensive approach involving collaboration between dentists and healthcare providers is imperative for holistic patient care. Implementing screening protocols for osteoporosis in dental settings and meticulously planning dental procedures for patients undergoing osteoporosis treatments are vital aspects of clinical practice. This review also sheds light on emerging trends in osteoporosis research, such as the influence of genetic factors and the microbiome, emphasizing the necessity for innovative treatment modalities. In conclusion, the review provides valuable insights into the nuanced connections between osteoporosis and oral health, thereby laying a foundation for informed clinical practices and guiding future research initiatives. Furthermore, it highlights the importance of optimizing dental procedures and assessing long-term oral health outcomes as critical avenues for future research endeavors.