Whole-genome sequencing drug susceptibility testing is associated with positive MDR-TB treatment response.

Until recently, multidrug-resistant TB (MDR-TB) was treated with lengthy and toxic regimens. New three-drug anti-TB regimens raise the question of whether they are sufficiently active for MDR-TB in Central Asia, an MDR-TB hotspot region.In a cohort of rifampicin-resistant (RR) and MDR-TB patients in the Kyrgyz Republic, we investigated the impact of the number of drugs that were tested susceptible by whole-genome sequencing (WGS) and conventional drug susceptibility testing (DST) and used for treatment on the treatment response, defined as 'matches'.

Temperature stability and enhanced transport properties by surface modifications of silica nanoparticle tracers for geo-reservoir exploration.

Tracer tests are an important tool for characterizing and monitoring subsurface reservoir properties. However, they are limited both because of the tracer molecules constraining factors such as irreversible adsorption, retention, and degradations, i.e.

Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy.

Background: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in heart failure if left untreated. Here, we hypothesized that the membrane fusion and repair protein dysferlin is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy.

Methods: Stimulated emission depletion and electron microscopy were used to localize dysferlin in mouse and human cardiomyocytes.

Ca1.3 channel clusters characterized by live-cell and isolated plasma membrane nanoscopy.

A key player of excitable cells in the heart and brain is the L-type calcium channel Ca1.3. In the heart, it is required for voltage-dependent Ca-signaling, i.

3D Super-Resolution Nuclear Q-FISH Imaging Reveals Cell-Cycle-Related Telomere Changes.

We present novel workflows for Q-FISH nanoscopy with the potential for prognostic applications and resolving novel chromatin compaction changes. DNA-fluorescence in situ hybridization (DNA-FISH) is a routine application to visualize telomeres, repetitive terminal DNA sequences, in cells and tissues. Telomere attrition is associated with inherited and acquired diseases, including cancer and cardiomyopathies, and is frequently analyzed by quantitative (Q)-FISH microscopy.

Challenging the gold standard: the limitations of molecular assays for detection of heteroresistance.

Objectives: Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In (), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).

Timing and precision of rattlesnake spinal motoneurons are determined by the KV7 potassium channel.

The evolution of novel motor behaviors requires modifications in the central pattern generators (CPGs) controlling muscle activity. How such changes gradually lead to novel behaviors remains enigmatic due to the long time course of evolution. Rattlesnakes provide a unique opportunity to investigate how a locomotor CPG was evolutionarily modified to generate a novel behavior-in this case, acoustic signaling.

Case Report: Fetoscopic Laparoschisis (FETO-LAP)-A New Therapeutic Route to Explore for Fetuses with Severe Diaphragmatic Hernias.

Background: The purpose of this report is to describe the seminal case of a near-term human fetus with a life-threatening left diaphragmatic hernia that underwent fetoscopic tracheal occlusion (FETO) combined with fetoscopic partial removal of herniated bowel from the fetal chest by fetoscopic laparoschisis (FETO-LAP).

Case Summary: A life-threatening left diaphragmatic hernia (liver-up; o/e LHR of ≤25%; MRI lung volume ≤ 20%) was observed in a human fetus at 34 weeks of gestation. After counselling the mother about the high risks of postnatal demise if left untreated, the expected limitations of fetoscopic tracheal occlusion (FETO), and the previously untested option of combining FETO with fetoscopic laparoschisis, i.

Blind spot in endocarditis guidelines: prosthetic valve endocarditis after cardiac surgery-a case series.

Background: The recently published 2023 Duke-ISCVID Criteria for Infective Endocarditis for the first time consider mycobacteria (esp. ) as 'typical' microorganisms for prosthetic valve endocarditis (major criteria). This reflects the ongoing worldwide outbreak of prosthetic valve endocarditis.

Transmission Dynamics of a Mycobacterium tuberculosis Complex Outbreak in an Indigenous Population in the Colombian Amazon Region.

Whole genome sequencing (WGS) has become the main tool for studying the transmission of Mycobacterium tuberculosis complex (MTBC) strains; however, the clonal expansion of one strain often limits its application in local MTBC outbreaks. The use of an alternative reference genome and the inclusion of repetitive regions in the analysis could potentially increase the resolution, but the added value has not yet been defined. Here, we leveraged short and long WGS read data of a previously reported MTBC outbreak in the Colombian Amazon Region to analyze possible transmission chains among 74 patients in the indigenous setting of Puerto Nariño (March to October 2016).

EXITitis in the UK: Gravity Estimates in the Aftermath of Brexit.

The withdrawal of the United Kingdom from the European Union has had disruptive effects on international trade. As part of its 'Global Britain' strategy in the wake of Brexit, the UK is pursuing a series of Free Trade Agreements with countries around the world, including Canada, Japan, Korea, Mexico, Norway, Switzerland, Turkey and possibly the United States. Closer to home, the UK is under mounting pressure to dissuade Scotland, Northern Ireland and Wales from seeking independence to regain the severed ties with the EU.

Multi-Dimensional Machine Learning Analysis of Polyaniline Films Using Stitched Hyperspectral ToF-SIMS Data.

The self-organizing map with relational perspective mapping (SOM-RPM) is an unsupervised machine learning method that can be used to visualize and interpret high-dimensional hyperspectral data. We have previously used SOM-RPM for the analysis of time-of-flight secondary ion mass spectrometry (ToF-SIMS) hyperspectral images and three-dimensional (3D) depth profiles. This provides insightful visualization of features and trends of 3D depth profile data, using a slice-by-slice view, which can be useful for highlighting structural flaws including molecular characteristics and transport of contaminants to a buried interface and characterization of spectra.

Clinical characteristics and outcome of Mycobacterium chimaera infections after cardiac surgery: systematic review and meta-analysis of 180 heater-cooler unit-associated cases.

Objectives: Since 2013, heater-cooler unit (HCU) associated Mycobacterium chimaera infections linked to a global outbreak have been described. These infections were characterised by high morbidity and mortality due to delayed diagnosis, as well as challenges in antimycobacterial and surgical therapy. This study aimed to investigate the clinical characteristics and outcome of published cases of HCU-associated M.

Enteric neuroanatomy and smooth muscle activity in the western diamondback rattlesnake (Crotalus atrox).

Background: Gastrointestinal (GI) functions are controlled by the enteric nervous system (ENS) in vertebrates, but data on snakes are scarce, as most studies were done in mammals. However, the feeding of many snakes, including Crotalus atrox, is in strong contrast with mammals, as it consumes an immense, intact prey that is forwarded, stored, and processed by the GI tract. We performed immunohistochemistry in different regions of the GI tract to assess the neuronal density and to quantify cholinergic, nitrergic, and VIPergic enteric neurons.

Lifesaving Treatments for the Tiniest Patients-A Narrative Description of Old and New Minimally Invasive Approaches in the Arena of Fetal Surgery.

Fetal surgery has become a lifesaving reality for hundreds of fetuses each year. The development of a formidable spectrum of safe and effective minimally invasive techniques for fetal interventions since the early 1990s until today has led to an increasing acceptance of novel procedures by both patients and health care providers. From his vast personal experience of more than 20 years as one of the pioneers at the forefront of clinical minimally invasive fetal surgery, the author describes and comments on old and new minimally invasive approaches, highlighting their lifesaving or quality-of-life-improving potential.

Direct proteomic and high-resolution microscopy biopsy analysis identifies distinct ventricular fates in severe aortic stenosis.

The incidence of aortic valve stenosis (AS), the most common reason for aortic valve replacement (AVR), increases with population ageing. While untreated AS is associated with high mortality, different hemodynamic subtypes range from normal left-ventricular function to severe heart failure. However, the molecular nature underlying four different AS subclasses, suggesting vastly different myocardial fates, is unknown.

Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis.

Transmission-driven multi-/extensively drug resistant (M/XDR) tuberculosis (TB) is the largest single contributor to human mortality due to antimicrobial resistance. A few major clades of the Mycobacterium tuberculosis complex belonging to lineage 2, responsible for high prevalence of MDR-TB in Eurasia, show outstanding transnational distributions. Here, we determined factors underlying the emergence and epidemic spread of the W148 clade by genome sequencing and Bayesian demogenetic analyses of 720 isolates from 23 countries.