PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

IgLON5-IgG: Innocent Bystander or Perpetrator?

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau () H1/H1 genotype as seen in other sporadic tauopathies.

Atypical brain MRI findings in a patient with treatment responsive anti-IgLON5 disease.

Anti-IgLON5 disease is a rare autoimmune neurological condition which was relatively recently described in the literature. This syndrome encompasses a range of clinical manifestations with most cases showing unremarkable findings on brain magnetic resonance imaging (MRI). Here, we report a case of a 61-year-old female patient with unique brain MRI features that, to the best of our knowledge, has not been reported in the literature before.

Analysis of the limited accessory genome reveals potential pitfalls of pan-genome analysis approaches.

Pan-genome analysis is a fundamental tool for studying bacterial genome evolution; however, the variety of methods used to define and measure the pan-genome poses challenges to the interpretation and reliability of results. To quantify sources of bias and error related to common pan-genome analysis approaches, we evaluated different approaches applied to curated collection of 151 ( ) isolates. is characterized by its clonal evolution, absence of horizontal gene transfer, and limited accessory genome, making it an ideal test case for this study.

Statistical Evaluation of ERG Responses: A New Method to Validate Cycle-by-Cycle Recordings in Advanced Retinal Degenerations.

Purpose: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses.

Methods: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data.

Establishing Fully-Automated Fundus-Controlled Dark Adaptometry: A Validation and Retest-Reliability Study.

Purpose: The purpose of this study was to establish and validate a novel fundus-controlled dark-adaptometry method.

Methods: We developed a custom dark-adaptometry software for the S-MAIA device using the open-perimetry-interface. In the validation-substudy, participants underwent dark-adaptometry testing with a comparator device (MonCvONE, 59% rhodopsin bleach, cyan and red stimuli centered at 2 degrees, 4 degrees, and 6 degrees eccentricity).

Lineage classification and antitubercular drug resistance surveillance of by whole-genome sequencing in Southern India.

Studies mapping genetic heterogeneity of clinical isolates of for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of in Southern India. We report several genetic variations in that may confer resistance to antitubercular drugs.

Genotype-Phenotype Association in ABCA4-Associated Retinopathy.

Stargardt disease (STGD1) is the most common inherited retina degeneration. It is caused by biallelic ABCA4 variants, and no treatment is available to date. STGD1 shows marked phenotypic variability, especially regarding the age of onset.

LOW-DOSE SUPPLEMENTATION WITH RETINOL IMPROVES RETINAL FUNCTION IN EYES WITH AGE-RELATED MACULAR DEGENERATION BUT WITHOUT RETICULAR PSEUDODRUSEN.

Purpose: The aim of this study was to determine the functional impact of oral vitamin A supplementation in patients with intermediate age-related macular degeneration with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation.

Methods: Five patients with intermediate age-related macular degeneration and without RPD (AMD group; mean ± SD age 78.0 ± 4.

Natural History of Visual Dysfunction in ABCA4 Retinopathy and Its Genetic Correlates.

Purpose: To systematically assess the ability to detect change and retest reliability for a panel of visual function assessments in ABCA4 retinopathy.

Design: Prospective natural history study (NCT01736293).

Methods: Patients with at least 1 documented pathogenic ABCA4 variant and a clinical phenotype consistent with ABCA4 retinopathy were recruited from a tertiary referral center.

Self-Hybridization in Leishmania major.

Genetic exchange between different strains in the sand fly vector has been experimentally demonstrated and is supported by population genetic studies. In nature, opportunities for interstrain mating are restricted to flies biting multiply infected hosts or through multiple bites of different hosts. In contrast, self-mating could occur in any infected sand fly.

Deep Learning-Based Modeling of the Dark Adaptation Curve for Robust Parameter Estimation.

Purpose: This study investigates deep-learning (DL) sequence modeling techniques to reliably fit dark adaptation (DA) curves and estimate their key parameters in patients with age-related macular degeneration (AMD) to improve robustness and curve predictions.

Methods: A long-short-term memory autoencoder was used as the DL method to model the DA curve. The performance was compared against the classical nonlinear regression method using goodness-of-fit and repeatability metrics.

Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics.

Choroideremia is an X-linked, blinding retinal degeneration with progressive loss of photoreceptors, retinal pigment epithelial (RPE) cells, and choriocapillaris. To study the extent to which these layers are disrupted in affected males and female carriers, we performed multimodal adaptive optics imaging to better visualize the in vivo pathogenesis of choroideremia in the living human eye. We demonstrate the presence of subclinical, widespread enlarged RPE cells present in all subjects imaged.

Genomic surveillance of Salmonella spp. in the Philippines during 2013-2014.

Background: Increasing antimicrobial resistance (AMR) in Salmonella has been observed in the Philippines. We aimed to characterise the population and AMR mechanisms of Salmonella with whole genome sequencing (WGS) and compare it with laboratory surveillance methods.

Methods: The serotype, multilocus sequence type, AMR genes and relatedness between isolates were determined from the genomes of 148 Salmonella Typhi (S.

Photoreceptor and Retinal Pigment Epithelium Relationships in Eyes With Vitelliform Macular Dystrophy Revealed by Multimodal Adaptive Optics Imaging.

Purpose: To assess the structure of cone photoreceptors and retinal pigment epithelial (RPE) cells in vitelliform macular dystrophy (VMD) arising from various genetic etiologies.

Methods: Multimodal adaptive optics (AO) imaging was performed in 11 patients with VMD using a custom-assembled instrument. Non-confocal split detection and AO-enhanced indocyanine green were used to visualize the cone photoreceptor and RPE mosaics, respectively.

Scotopic Contour Deformation Detection Reveals Early Rod Dysfunction in Age-Related Macular Degeneration With and Without Reticular Pseudodrusen.

Purpose: The purpose of this study was to investigate scotopic contour deformation detection (sCDD), and its structural determinants, in participants with intermediate age-related macular degeneration (iAMD) with or without reticular pseudodrusen (RPD).

Methods: Forty-one participants (aged 58-89 years), including 9 with iAMD and RPD, 16 with iAMD only, and 16 controls, underwent functional testing. The sCDD was evaluated with radial frequency arcs presented at 4 loci: ±4 degrees and 8 degrees vertical eccentricity.

Clinical Phenotypes of -Associated Retinal Dystrophies.

The retinal dystrophy phenotype associated with retinopathy is clinically heterogenous. In this study, we describe the clinical and molecular findings of a retinal dystrophy cohort (10 patients) attributed to autosomal recessive and report novel variants in populations not previously identified with -related retinopathy. Seven patients had evaluations covering at least a three-year period.

ISCEV Standard for full-field clinical electroretinography (2022 update).

The full-field electroretinogram (ERG) is a mass electrophysiological response to diffuse flashes of light and is used widely to assess generalized retinal function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical ERG testing. Minimum protocols for basic ERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis, monitoring and inter-laboratory comparisons, while also responding to evolving clinical practices and technology.

Efficacy and Safety of a Krabbe Disease Gene Therapy.

Krabbe disease is a lysosomal storage disease caused by mutations in the gene that encodes galactosylceramidase, in which galactosylsphingosine (psychosine) accumulation drives demyelination in the central and peripheral nervous systems, ultimately progressing to death in early childhood. Gene therapy, alone or in combination with transplant, has been developed for almost two decades in mouse models, with increasing therapeutic benefit paralleling the improvement of next-generation adeno-associated virus (AAV) vectors. This effort has recently shown remarkable efficacy in the canine model of the disease by two different groups that used either systemic or cerebrospinal fluid (CSF) administration of AAVrh10 or AAV9.

Dark Adaptation and Its Role in Age-Related Macular Degeneration.

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD).

Genomic surveillance of in the Philippines, 2013-2014.

Objective: is an opportunistic nosocomial pathogen that has increasingly become resistant to carbapenems worldwide. In the Philippines, rates of carbapenem resistance and multidrug resistance are above 50%. We undertook a genomic study of carbapenem-resistant in the Philippines to characterize the population diversity and antimicrobial resistance mechanisms.

In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells.

T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction and are crucial for the generation of robust, long-lived antibody responses, but how the GC microenvironment affects Tfh cells is not well understood. Here we develop an in vivo T cell-intrinsic CRISPR-knockout screen to evaluate Tfh and Th1 cells in an acute viral infection model to identify regulators of Tfh cells in their physiological setting. Using a screen of druggable-targets, alongside genetic, transcriptomic and cellular analyses, we identify a function of HIF-1α in suppressing mTORC1-mediated and Myc-related pathways, and provide evidence that VHL-mediated degradation of HIF-1α is required for Tfh development; an expanded in vivo CRISPR screen reveals multiple components of these pathways that regulate Tfh versus Th1 cells, including signaling molecules, cell-cycle regulators, nutrient transporters, metabolic enzymes and autophagy mediators.

Patterns of genomic interrelatedness of publicly available samples in the TB portals database.

The TB Portals program is an international collaboration for the collection and dissemination of tuberculosis data from patient cases focused on drug resistance. The central database is a patient-oriented resource containing both patient and pathogen clinical and genomic information. Herein we provide a summary of the pathogen genomic data available through the TB Portals and show one potential application by examining patterns of genomic pairwise distances.