A physico-chemical rationale for the varied catalytic efficiency in RNase J paralogues.

Paralogues of the bifunctional nuclease, Ribonuclease J (RNase J) demonstrate varied catalytic efficiencies despite extensive sequence and structural similarity. Of the two S. aureus RNase J paralogues, RNase J1 is substantially more active than RNase J2.

Nucleophilic Ring Opening of Donor-Acceptor Cyclopropanes through Umpolung Reactivity of Organochlorophosphines: Phosphine Oxide-Functionalized Boron-Pendanted Compounds.

We present a novel set of frustrated Lewis pair (FLP) systems that exhibit a remarkable ability to promote the ring opening of donor-acceptor cyclopropanes (DACs). This FLP-promoted protocol offers umpolung reactivity of RRPCl/CN (R, R = aryl, alkyl) toward DACs via nucleophilic ring-opening reactions to provide phosphinated boron-pendanted diester compounds. This novel approach exhibits the dual role of BF·OEt as an activator and a reactant.

Costs and cost-effectiveness of the Kerala pilot screening programme for diabetic retinopathy in the public health system.

Background/objectives: The Government of Kerala initiated a pilot screening programme for diabetic retinopathy in 16 Family Health Centres in Thiruvananthapuram district in 2019 in collaboration with the ORNATE India project. The evaluation of this pilot included a study of its costs and cost-effectiveness to inform decisions about extending the programme throughout Kerala.

Subjects/methods: The participants comprise all 5307 people who were screened for diabetic retinopathy under the pilot programme for whom data could be collected.

Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA).

Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication.

Methods: The intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use.

Training in Cultural Competence for Mental Health Care: A Mixed-Methods Study of Students, Faculty, and Practitioners from India and USA.

Although the need to train clinicians to provide effective mental health care to individuals from diverse backgrounds has been recognized worldwide, a bulk of what we know about training in cultural competence (CC) is based on research conducted in the United States. Research on CC in mental health training from different world populations is needed due to the context-dependent nature of CC. Focusing on India and USA, two diverse countries that provide complementary contexts to examine CC, we explored graduate students', practicing clinicians', and faculty members' perspectives regarding CC training they received/provided and future training needs using mixed-methods.

Disposition Outcomes Following Prehospital Use of Naloxone in a Large Metropolitan City in the United States.

Objectives: During a drug overdose, research suggests individuals may not call 9-1-1 out of fear of criminal justice concerns. Of those that call, research is inconclusive about the disposition of the emergency transport. We evaluated transport outcomes for adults with opioid-related overdose in the Emergency Medical Services (EMS) of a large metropolitan city in the United States.

Generalized Arterial Calcification of Infancy Mimicking Coarctation of Aorta in a Neonate.

Generalized arterial calcification of infancy (GACI) is a rare genetic condition with varied clinical presentation. Consequently, diagnosis is frequently delayed or missed. GACI has a poor prognosis, with more than half of patients dying before the age of 6 months.

Self-driving autonomous machines to engineer novel enzymes.

Can one design and automate a computational and experimental platform such that each platform iteratively guides and drives the other to achieve a pre-determined goal? Rapp and colleagues (2024) describe just this possibility in a paper that details a prototype of a self-driven laboratory that can navigate autonomously to yield an engineered enzyme with a desired attribute. This laboratory, rather, the automated protocol, is referred to by an acronym - SAMPLE. This refers to Self-driving Autonomous Machines for Protein Landscape Exploration.

Design of a tunable bacterial gene expression system using engineered σ factors.

Unlabelled: Extracytoplasmic function (ECF) σ factors selectively upregulate expression of specific genes in bacteria. These σ factors, belonging to the σ family, are much smaller than the primary, housekeeping σ factor with two helical domains that interact with the Pribnow box and the -35 element of the promoter DNA. Structural studies reveal that promoter specificity in a σ factor is determined by the interactions between a loop (L3) and the Pribnow box element.

Development and Effect of a Coordinated Community Health Worker Intervention Model for the Stroke Survivors in Kerala, South India.

Introduction: Structured models for secondary prevention of stroke in community settings are scarce. We aimed to develop and evaluate a model for improving medication adherence and enhanced risk factor monitoring.

Methods: We developed a multimodal coordinated community health worker (CHW) intervention (C-CHW-I) model for stroke survivors.

Stroke awareness among community health workers from rural health blocks of Thiruvananthapuram, India.

Objectives: Secondary prevention of stroke largely depends on risk factor control and lifestyle modification. Optimal secondary prevention strategies are limited in rural settings due to the shortage of primary care physicians and neurologists. Awareness of community health workers (CHWs) regarding stroke and its management remains largely unexplored.

Characterization of RNase J.

RNase J is involved in RNA maturation as well as degradation of RNA to the level of mononucleotides. This enzyme plays a vital role in maintaining intracellular RNA levels and governs different steps of the cellular metabolism in bacteria. RNase J is the first ribonuclease that was shown to have both endonuclease and 5'-3' exonuclease activity.

Helping Frontline Workers in Texas-A Framework for Resource Development.

First responders disproportionately experience occupational stress when compared to the general population, and COVID-19 has exacerbated this stress. The nature of their duties as law enforcement officers, firefighters, and medics exposes them to repeated trauma, increasing their risk of developing a broad array of mental health issues, including post-traumatic stress disorder (PTSD), substance use disorder (SUD), and compassion fatigue. This paper describes the need for resources for frontline workers and provides a framework for creating and implementing resources.

Impostor Phenomenon Among Family Medicine Residency Program Directors: A CERA Study.

Background And Objectives: Impostor phenomenon (IP) can be described as feelings of inadequacy that exist despite apparent success. Although IP may be related to multiple important outcomes in physicians, it has not been examined among residency program directors (PDs).

Methods: The seven-item Leary Impostorism Scale (LIS) was added to the 2021 Council of Academic Family Medicine Educational Research Alliance (CERA) PD survey.

Crystal structures of non-uracil ring fragments in complex with Mycobacterium tuberculosis uracil DNA glycosylase (MtUng) as a starting point for novel inhibitor design: A case study with the barbituric acid fragment.

Uracil DNA glycosylase (UDG or Ung) is a key enzyme involved in uracil excision from the DNA as a repair mechanism. Designing Ung inhibitors is thus a promising strategy to treat different cancers and infectious diseases. The uracil ring and its derivatives have been shown to inhibit Mycobacterium tuberculosis Ung (MtUng), resulting from specific and strong binding with the uracil-binding pocket (UBP).

Allosteric Determinants in High Temperature Requirement A Enzymes Are Conserved and Regulate the Population of Active Conformations.

High temperature requirement A (HtrA) are allosterically regulated enzymes wherein effector binding to the PDZ domain triggers proteolytic activity. Yet, it remains unclear if the inter-residue network governing allostery is conserved across HtrA enzymes. Here, we investigated and identified the inter-residue interaction networks by molecular dynamics simulations on representative HtrA proteases, DegS and PepD, in effector-bound and free forms.

Mutational and structural analyses of UdgX: insights into the active site pocket architecture and its evolution.

UdgX excises uracil from uracil-containing DNA to concurrently form a covalent bond with the resulting AP-DNA. Structurally, UdgX is highly similar to family-4 UDGs (F4-UDGs). However, UdgX is unique in possessing a flexible R-loop (105KRRIH109).

The unique N-terminal region of Mycobacterium tuberculosis sigma factor A plays a dominant role in the essential function of this protein.

SigA (σ) is an essential protein and the primary sigma factor in Mycobacterium tuberculosis (Mtb). However, due to the absence of genetic tools, our understanding of the role and regulation of σ activity and its molecular attributes that help modulate Mtb survival is scant. Here, we generated a conditional gene replacement of σ in Mtb and showed that its depletion results in a severe survival defect in vitro, ex vivo, and in vivo in a murine infection model.