A streamlined CRISPR-based test for tuberculosis detection directly from sputum.

() is a major threat to global health, and there is an urgent need for affordable, simple tuberculosis (TB) diagnosis in underresourced areas. Here, we combine recombinase polymerase amplification with Cas13a and Cas12a detection to create two parallelized one-pot assays that detect two conserved elements of ( and ) and a human DNA internal control. These assays are compatible with lateral flow and can be readily lyophilized.

Clinicopathological Spectrum of Myxoid Soft Tissue Tumours with Emphasis on Diagnostic Differentials.

Objectives: Myxoid soft tissue tumours (MSTTs) represent a complex group of mesenchymal neoplasms characterised by the production of an extracellular myxoid matrix, which often poses diagnostic challenges. This study aimed to identify the relative frequency, distribution and morphological spectrum of MSTT as well as to illustrate commonly encountered diagnostic difficulties.

Methods: This retrospective study of the clinicopathological profiles of MSTT cases at Sri Aurobindo Medical College & Post Graduate Institute, Indore, India, was conducted from January 2020 to December 2023.

Differential Expression of TLE1 in Small Round Cell Tumors: A Proposed Solution for Challenging Differentials Impacting Treatment Strategies.

Small round cell tumors (SRCTs) represent a heterogeneous group of neoplasms with overlapping histological features but varying origins, prognoses, and treatments. TLE1 is a well-established marker for synovial sarcoma (SS). However, TLE1's diagnostic utility is limited by its expression in a broad range of tumor types, reducing its specificity for SS.

Prominence of Mycobacterium tuberculosis biomarkers among sputum culture-negative clinic attendees, independent of Ultra status.

Background: Highly-sensitive molecular tests like GeneXpert MTB/RIF Ultra improve detection of paucibacillary pulmonary tuberculosis (TB) but occasionally detect Mycobacterium tuberculosis (Mtb) DNA in sputum from culture-negative individuals, with unclear significance. We hypothesized that Ultra may be detecting culture-negative TB, and manifest in a higher prevalence of TB biomarkers compared to Ultra-negative/culture-negative ('sputum-negative') individuals.

Methods: From 1200 symptomatic African adults undergoing evaluation for TB, we identified 66 with discordant results (Ultra-positive, culture-negative), and matched 52 sputum-negative (Ultra-negative, culture-negative) and 30 sputum-positive (Ultra-positive, culture-positive) participants.

Simplified Co-extraction of total Nucleic Acids from Respiratory Samples for detection of and SARS-CoV-2 optimized for compatibility across Diagnostic Platforms.

Tuberculosis (TB) and COVID-19 are leading infectious diseases with high mortality, caused by and , respectively. Co-infection is common but is often undiagnosed as it is challenging to process both pathogens from a single sample. In this study, we present a simple and efficient method for co-extracting nucleic acids (NA) from these two distinct respiratory pathogens for downstream diagnostic testing.

Engineering Protein-Polyelectrolyte Interactions for Cellular Applications.

Protein-polyelectrolyte interactions are fundamental interactions in biology that occur at every length scale, from protein-DNA complexes to phase-separated organelles. They drive processes ranging from gene transcription and DNA synthesis to viral assembly. Protein engineering is a powerful way to modulate these interactions, both to probe endogenous function and to engineer novel interactions between species.

The phases of transition from fluoroscopy to ultrasound-guided pain medicine interventions.

Ultrasonography (USG)-guided interventions have transformed pain medicine by enhancing precision, efficacy, and safety through real-time anatomical visualization. Despite these advantages, mastering USG techniques presents a steep learning curve, especially for practitioners transitioning from fluoroscopy-guided methods. Adapting the Transtheoretical Model of Behavior Change, this commentary outlines a five-phase framework for transitioning to USG-guided pain medicine interventions: overcoming initial reluctance, addressing sonoanatomy challenges, improving probe stabilization, needle visualization, and achieving expertise.

A Streamlined Point-of-Care CRISPR Test for Tuberculosis Detection Directly from Sputum.

() is a major threat to global health and is responsible for over one million deaths each year. To stem the tide of cases and maximize opportunities for early interventions, there is an urgent need for affordable and simple means of tuberculosis diagnosis in under-resourced areas. We sought to develop a CRISPR-based isothermal assay coupled with a compatible, straightforward sample processing technique for point-of-care use.

Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine.

Tuberculosis (TB) remains one of the leading global causes of mortality. Several methods have been established to detect anti-TB agents in human plasma and serum. However, there is a notable absence of studies analyzing TB drugs in urine.

Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled.

New approach to rifampicin stability and first-line anti-tubercular drug pharmacokinetics by UPLC-MS/MS.

Successful tuberculosis (TB) therapy requires achieving sufficient exposure to multiple drugs. Limited stability of several first-line anti-TB drugs might compromise reliable therapeutic drug monitoring (TDM). We developed and validated a sensitive and selective UPLC-MS/MS method for simultaneous quantification of isoniazid (INH), pyrazinamide (PZA), rifampicin (RIF), its metabolite 25-desacetylrifampicin and degradation products: rifampicin quinone and 3-formyl-rifampicin.

Designing negative feedback loops in enzymatic coacervate droplets.

Membraneless organelles within the living cell use phase separation of biomolecules coupled with enzymatic reactions to regulate cellular processes. The diverse functions of these biomolecular condensates motivate the pursuit of simpler models that exhibit primitive forms of self-regulation based on internal feedback mechanisms. Here, we investigate one such model based on complex coacervation of the enzyme catalase with an oppositely charge polyelectrolyte DEAE-dextran to form pH-responsive catalytic droplets.

Alternative Methods for Therapeutic Drug Monitoring and Dose Adjustment of Tuberculosis Treatment in Clinical Settings: A Systematic Review.

Background And Objective: Quantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or toxicity due to individual variability in pharmacokinetics. Traditionally, serum or plasma samples have been used for drug monitoring, which only poses collection and logistical challenges in high-tuberculosis burden/low-resourced areas. Less invasive and lower cost tests using alternative biomatrices other than serum or plasma may improve the feasibility of therapeutic drug monitoring.

An unusual case of paediatric plasmablastic lymphoma presenting with malignant effusion and the challenges in its diagnosis.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma occurring commonly in the oral mucosa and jaw of human immunodeficiency virus (HIV) positive adult males. PBL is not a common occurrence in children and a presentation with malignant effusion is rarely reported. Herein, we share our experience in the challenges confronted in the diagnosis of PBL in a 6-year-old, HIV positive boy presenting with malignant pleural and peritoneal effusions along with gum hypertrophy, lymphadenopathy and paranasal sinus mass.