Chaperone-mediated heterotypic phase separation regulates liquid-to-solid phase transitions of tau into amyloid fibrils.

Biomolecular condensates formed via phase separation of proteins, and nucleic acids regulate crucial cellular processes. However, such liquid-like membraneless bodies can undergo aberrant liquid-to-solid transitions into amyloid-like pathological species, which necessitates their efficient clearance by the cellular protein quality control machinery comprising molecular chaperones. We present a unique case to demonstrate that a heat shock protein 40 (Ydj1) promotes the heterotypic phase separation of intrinsically disordered tau via a multitude of interactions.

Profile of monogenic diabetes: a Pan-India study.

Aim: To evaluate the frequency of monogenic diabetes mutations among individuals clinically suspected to have monogenic diabetes in India.

Methods: Participants (n = 774) were recruited from 65 diabetes centres across India (http://monogenicdiabetes.in/Collaborators.

Advancing tuberculosis elimination in India: A qualitative review of current strategies and areas for improvement in tuberculosis preventive treatment.

Tuberculosis (TB), caused by , remains a global health challenge, despite being preventable and curable. The global goal to end TB by 2030, with India targeting a 90% reduction in TB incidence by 2025, demands comprehensive interventions in prevention, early detection, treatment, and capacity building. This study analyzes the 2023 Global TB Reports, published articles, guidelines, and data to explore India's current TB landscape.

Chaperone-Mediated Heterotypic Phase Separation Prevents the Amyloid Formation of the Pathological Y145Stop Prion Protein Variant.

Biomolecular condensates formed via phase separation of proteins and nucleic acids are crucial for the spatiotemporal regulation of a diverse array of essential cellular functions and the maintenance of cellular homeostasis. However, aberrant liquid-to-solid phase transitions of such condensates are associated with several fatal human diseases. Such dynamic membraneless compartments can contain a range of molecular chaperones that can regulate the phase behavior of proteins involved in the formation of these biological condensates.

Successful Endoscopic Management of Complete Tracheal Occlusion in a Child.

Prolonged mechanical ventilation following cardiopulmonary and neurological events oftentimes necessitates a tracheostomy and tracheal granulation is one of its most common late complications. The literature recommends that large granulation be managed through surgical excision or endoluminal techniques. A 6-year-old boy presented with high-grade tracheal stenosis secondary to endotracheal cuff-related injury and prolonged tracheostomy.

Hydrogen-Bonded Network of Water in Phase-Separated Biomolecular Condensates.

Biomolecular condensates formed via phase separation of intrinsically disordered proteins/regions (IDPs/IDRs) and nucleic acids are associated with cell physiology and disease. Water makes up for ∼60-70% of the condensate volume and is thought to influence the complex interplay of chain-chain and chain-solvent interactions, modulating the mesoscale properties of condensates. The behavior of water in condensates and the key roles of protein hydration water in driving the phase separation remain elusive.

Predictors for Concurrent Diabetes in Tuberculosis Patients. Perspectives from Two Mining Districts of Eastern Tribal State Jharkhand, in India.

Background: Tuberculosis and diabetes both diseases are present in large numbers in the country and we are major contributors to both globally. With the objective to understand the various traits of patients having both tuberculosis and diabetes and to ascertain various possible predictors for such occurrence based on the public health database we carried out this study. We seek answers to questions like they have any effects? Are they having any additive role to play?

Methods: One-year data from the NIKSHAY portal of both districts were analyzed to look for possible associations and other variable traits.

Masquerading fungal bowel mass in an adolescent: a clinicopathological challenge.

Abdominal masses clubbed with weight loss in the paediatric age group can raise hairs, especially since malignancy is a differential. We present the case of an early adolescent male who presented with abdominal pain and was found to have a mass mimicking a malignancy. The resected surgical specimen revealed entomophthoromycosis of the jejunum and he made a complete recovery following surgery and adjuvant itraconazole.

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10-colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity.

Introduction: Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing.

Materials And Methods: Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3.

Bridging the Gap: A Strategic Approach to Upscale Knowledge Among Diverse Healthcare Providers for Effective Tuberculosis Management in Gujarat, India.

Introduction: Tuberculosis (TB) remains a global health challenge, particularly in low- and middle-income countries. Knowledge gaps among healthcare providers (HCPs) significantly impact TB management, hindering timely care-seeking and effective interventions.

Objective: The primary objective was to assess knowledge gaps among 3086 HCPs engaged in the National Tuberculosis Elimination Program (NTEP) implementation in Gujarat, India.

Obstructing urethral membrane in a girl: a rare cause of female bladder outlet obstruction.

Bladder outlet obstruction is known to produce back pressure changes on the urinary tract with devastating sequelae more often than not. Among the causes, posterior urethral valve, which is the most common, is documented to occur exclusively in males. Female posterior urethral valves have been reported in the past in less than 25 cases in existing literature.

Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation.

Biomolecular condensates formed via phase separation of proteins and nucleic acids are thought to be associated with a wide range of cellular functions and dysfunctions. We dissect critical molecular events associated with phase separation of an intrinsically disordered prion-like low-complexity domain of Fused in Sarcoma by performing single-molecule studies permitting us to access the wealth of molecular information that is skewed in conventional ensemble experiments. Our single-molecule FRET experiments reveal the coexistence of two conformationally distinct subpopulations in the monomeric form.

Development and user acceptability testing of healthy heart mobile application - a tool for cardiovascular risk modification among patients with type 2 diabetes mellitus.

Objectives: Cardiovascular disease (CVD) remains the primary cause of mortality in individuals with type 2 diabetes mellitus. Digital health has quickly emerged as a technology with the ability to bridge the gap in cardiovascular disease self-management and revolutionize the way healthcare has traditionally been delivered. However, there is little data on the application of mobile technologies for cardiovascular risk reduction among diabetic patients.

Understanding Childhood Constipation through the Prism of the Caretaker.

Aims: Childhood constipation is presenting with increasing frequency at pediatric surgical clinics. The caregiver's role in prevention and management is pivotal. This study aimed at determining mothers' knowledge, attitudes, and practices with regard to childhood constipation and the association of these with demographic variables.

Acute myeloid leukemia with RAM immunophenotype: A new underdiagnosed entity.

Introduction: Acute myeloid leukemia (AML) with RAM immunophenotype is a distinct subtype of AML, as described by the Children's Oncology Group (COG), with characteristic morphological and immunophenotypic properties. It is characterized by strong CD56 expression with dim to negative CD45, HLA-DR, and CD38 expression. It is an aggressive leukemia with a poor response to induction chemotherapy and/or frequent relapses.

Heterotypic electrostatic interactions control complex phase separation of tau and prion into multiphasic condensates and co-aggregates.

Biomolecular condensates formed via phase separation of proteins and nucleic acids are thought to perform a wide range of critical cellular functions by maintaining spatiotemporal regulation and organizing intracellular biochemistry. However, aberrant phase transitions are implicated in a multitude of human diseases. Here, we demonstrate that two neuronal proteins, namely tau and prion, undergo complex coacervation driven by domain-specific electrostatic interactions to yield highly dynamic, mesoscopic liquid-like droplets.

Integrated single-cell transcriptome analysis of CD34 + enriched leukemic stem cells revealed intra- and inter-patient transcriptional heterogeneity in pediatric acute myeloid leukemia.

To gain insights into the idiosyncrasies of CD34 + enriched leukemic stem cells, we investigated the nature and extent of transcriptional heterogeneity by single-cell sequencing in pediatric AML. Whole transcriptome analysis of 28,029 AML single cells was performed using the nanowell cartridge-based barcoding technology. Integrated transcriptional analysis identified unique leukemic stem cell clusters of each patient and intra-patient heterogeneity was revealed by multiple LSC-enriched clusters differing in their cell cycle processes and BCL2 expression.

CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations.

Introduction: CD34 and HLA-DR negativity is often used as a characteristic immunophenotypic feature of acute promyelocytic leukaemia (APL) that differentiates APL from other subtypes of acute myeloid leukaemia (AML). However, other subtypes of AML, without expression of CD34 and HLA-DR antigens, have also been reported.

Methods: We analysed the HLA-DR negative de novo non-APL AML cases by dividing HLA-DR negative non-APL group into 2 sub-groups based on CD34 expression and compared the characteristics of CD34 negative HLA-DR negative with CD34 positive HLA-DR negative non-APL AML cases with respect to morphologic, immunophenotypic, molecular and clinical parameters.

Hypocellular AML versus MDS-diagnostic challenge case report with review of literature.

Hypocellular AML being a rare entity with considerable overlapping features and characteristics with various other entities brings a need to have a better and clear understanding of hypocellular AML to differentiate in the decision-making process for therapeutic patient management. With some degree of dysplasia inherently associated with AML it is challenging to differentiate hypocellular AML from Myelodysplastic syndromes. We present a case report where the diagnostic dilemma in an elderly male patient who presented with fever, pallor, weight loss and fatiguability.

Utility of CD229 as novel marker in measurable residual disease assessment in multiple myeloma-An evidence-based approach.

Introduction: CD229 has been found to be a useful plasma cell (PC) gating marker in multiple myeloma (MM). This study analyses the expression profile of CD229 on various bone marrow compartments namely, PC, non-PC and hematogones (HGs) using Multiparameter flow cytometry (MFC). Furthermore, it evaluates the ability of CD229 to delineate normal PC (NPC) from aberrant PC (APC) in measurable residual disease assessment (MRD) in MM.

The Syringe Technique for Ultrasound-Guided Hydrostatic Intussusception Reduction.

Background: Ultrasound-guided hydrostatic reduction (UGHR) is a well accepted and widely used method of paediatric intussusception reduction, with the saline drip technique being the most commonly employed.

Aims And Objectives: In this study we aimed to assess the outcomes of a novel technique of UGHR.

Materials And Methods: Data was obtained from a 15 year retrospective chart review of paediatric intussusceptions.

Relevance of polyclonal plasma cells and post-therapy immunomodulation in measurable residual disease assessment in multiple myeloma.

Background: Immunophenotypic profile and post-therapy alteration in antigenic expression were evaluated in normal, reactive, and aberrant plasma cells (NPC, RPC, and APC) for impact on measurable residual disease (MRD) assessment in multiple myeloma (MM).

Methods: Samples from non-MM staging marrow (n = 30), Hodgkin's lymphoma (n = 30) and MM (n = 724) were prospectively evaluated for expression profiles of NPC, RPC, and APC using antigens recommended in consensus guidelines.

Results: Polyclonal NPC-RPC demonstrated aberrations for all antigens evaluated with a higher frequency of aberrancies in post-therapy samples compared to treatment naïve samples (p < 0.