Retinal thinning differentiates treatment effects in relapsing multiple sclerosis below the clinical threshold.

Objective: To investigate retinal layer thinning as a biomarker of disease-modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).

Methods: From an ongoing prospective observational study, we included patients with RMS, who (i) had an optical coherence tomography (OCT) scan within 6 to 12 months after DMT start (rebaseline) and ≥1 follow-up OCT ≥12 months after rebaseline and (ii) adhered to DMT during follow-up. Differences between DMT in thinning of peripapillary-retinal-nerve-fiber-layer (pRNFL) and macular ganglion cell-plus-inner plexiform-layer (GCIPL) were analyzed using mixed-effects linear regression.

Women With Congenital Adrenal Hyperplasia Have Favorable Pregnancy Outcomes but Prolonged Time to Conceive.

Objective: To study pregnancy outcomes and complications in women with congenital adrenal hyperplasia (CAH).

Methods: A retrospective multicenter study was conducted at tertiary reference centers in 5 countries (Austria, Germany, Italy, Sweden, USA), including 72 adult women with CAH (nonclassic [NC] n = 34, simple virilizing [SV] n = 21, salt wasting [SW] n = 17).

Results: A total of 133 pregnancies, 112 live births, and 25 abortions were documented.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Repositioning Brusatol as a Transmission Blocker of Malaria Parasites.

Currently, primaquine is the only malaria transmission-blocking drug recommended by the WHO. Recent efforts have highlighted the importance of discovering new agents that regulate malarial transmission, with particular interest in agents that can be administered in a single low dose, ideally with a discrete and -selective mechanism of action. Here, our team demonstrates an approach to identify malaria transmission-blocking agents through a combination of screening and analyses.

Origin of biogeographically distinct ecotypes during laboratory evolution.

Resource partitioning is central to the incredible productivity of microbial communities, including gigatons in annual methane emissions through syntrophic interactions. Previous work revealed how a sulfate reducer (Desulfovibrio vulgaris, Dv) and a methanogen (Methanococcus maripaludis, Mm) underwent evolutionary diversification in a planktonic context, improving stability, cooperativity, and productivity within 300-1000 generations. Here, we show that mutations in just 15 Dv and 7 Mm genes within a minimal assemblage of this evolved community gave rise to co-existing ecotypes that were spatially enriched within a few days of culturing in a fluidized bed reactor.

Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity.

Background And Objectives: Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome.

Methods: Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI.

A Novel Confocal Scanning Protein-Protein Interaction Assay (PPI-CONA) Reveals Exceptional Selectivity and Specificity of CC0651, a Small Molecule Binding Enhancer of the Weak Interaction between the E2 Ubiquitin-Conjugating Enzyme CDC34A and Ubiquitin.

Protein-protein interactions (PPIs) are some of the most challenging target classes in drug discovery. Highly sensitive detection techniques are required for the identification of chemical modulators of PPIs. Here, we introduce PPI confocal nanoscanning (PPI-CONA), a miniaturized, microbead based high-resolution fluorescence imaging assay.

Addressing healthcare vulnerabilities in nursing homes : Insights from human rights monitoring in two Austrian provinces.

Background: Current demographic changes bear challenges for national care systems due to higher life expectancy of older citizens. Largely cut off from society, nursing home residents are at risk for violence, neglect, and other potential human rights violations. This study aimed to investigate healthcare vulnerabilities in nursing homes and evaluate the Austrian National Preventive Mechanism (NPM).

Survey of Potential Drug Interactions, Use of Non-Medical Health Products, and Immunization Status among Patients Receiving Targeted Therapies.

In recent years, several changes have occurred in the management of chronic immunological conditions with the emerging use of targeted therapies. This two-phase cross-sectional study was conducted through structured in-person interviews in 2018-2019 and 2022. Additional data sources included ambulatory medical records and the itemized reimbursement reporting interface of the National Health Insurance Fund.

ChatGPT With GPT-4 Outperforms Emergency Department Physicians in Diagnostic Accuracy: Retrospective Analysis.

Background: OpenAI's ChatGPT is a pioneering artificial intelligence (AI) in the field of natural language processing, and it holds significant potential in medicine for providing treatment advice. Additionally, recent studies have demonstrated promising results using ChatGPT for emergency medicine triage. However, its diagnostic accuracy in the emergency department (ED) has not yet been evaluated.

Simplified Volumetric Models as an Effective Strategy for Segmenting Actin Networks in Cryo-Electron Tomograms.

Efficient methods for the extraction of features of interest remain one of the biggest challenges for the interpretation of cryo-electron tomograms. Various automated approaches have been proposed, many of which work well for high-contrast datasets where the features of interest can be easily detected and are clearly separated from one another. Our inner ear stereocilia cryo-electron tomographic datasets are characterized by a dense array of hexagonally packed actin filaments that are frequently cross-connected.

Frequency of stress dosing and adrenal crisis in paediatric and adult patients with congenital adrenal hyperplasia: a prospective study.

Objective: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents.

Design: Prospective, observational study.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis.

Background: Olfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS).

Objective: To investigate whether OT predicts long-term MS clinical disease course.

Methods: This was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck.

Reduction in Nuclear Size by DHRS7 in Prostate Cancer Cells and by Estradiol Propionate in DHRS7-Depleted Cells.

Increased nuclear size correlates with lower survival rates and higher grades for prostate cancer. The short-chain dehydrogenase/reductase (SDR) family member DHRS7 was suggested as a biomarker for use in prostate cancer grading because it is largely lost in higher-grade tumors. Here, we found that reduction in DHRS7 from the LNCaP prostate cancer cell line with normally high levels of DHRS7 increases nuclear size, potentially explaining the nuclear size increase observed in higher-grade prostate tumors where it is lost.

Nudging Online Gamblers to Withdraw Money: The Impact of Personalized Messages on Money Withdrawal Among a Sample of Real-World Online Casino Players.

A number of scholars have argued that online gambling can be more problematic than land-based gambling. Motivating gamblers to withdraw money from their online gambling account could lower losses because there would be less money available to lose. Therefore, the present study investigated whether personalized messages are an effective way of 'nudging' gamblers to withdraw money from their online gambling account.

E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.

Purpose: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.

Methods: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls.

Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology.

Introduction: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency.

Multiple sclerosis in the elderly: a retrospective cohort study.

Background: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients.

Objective: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients.

Methods: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria.

Odour discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis.

Background: Odour discrimination and identification (DI) are markers associated with disability worsening and neuroaxonal damage in multiple sclerosis (MS).

Objective: The main objective of this research is to investigate whether longitudinal change of DI predicts long-term MS disease course.

Methods: This is a 6-year prospective longitudinal study on MS patients at the MS Clinic Innsbruck.

Nanoscaled Discovery of a Shunt Rifamycin from Using a Three-Color GFP-Tagged Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment.