DNA Triplet Energies by Free Energy Perturbation Theory.

Determining the energetics of triplet electronic states of nucleobases in the biological macromolecular environment of nucleic acids is essential for an accurate description of the mechanism of photosensitization and the design of drugs for cancer treatment. In this work, we aim at developing a methodological approach to obtain accurate free energies of triplets in DNA beyond the state of the art, able to reproduce the decrease of triplet energies measured experimentally for in DNA (270 kJ/mol) vs in the isolated nucleotide in aqueous solution (310 kJ/mol). For such purposes, we adapt the free energy perturbation method to compute the free energy related to the transformation of a pure singlet state into a pure triplet state via "alchemical" intermediates with mixed singlet-triplet nature.

Emergence of Invasive Streptococcus dysgalactiae subsp. equisimilis in Spain (2012-2022): Genomic Insights and Clinical Correlations.

Objectives: An increase in Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections has been documented worldwide. This study aims to analyse invasive disease caused by SDSE (iSDSE) in adults over an 11-year period in Spain.

Workshop report: Clinical training and integration of genetic counselors into interprofessional teams in the German-speaking countries.

In spring 2022, the inaugural cohort of Genetic and Genomic Counseling MSc students graduated from the Medical University of Innsbruck, representing a significant milestone for the establishment of the genetic counselor (GC) profession in the German-speaking countries. A pivotal component of their education was a 15-week clinical training period. The placement experiences of both students and supervisors offered valuable insights into the attitudes of medical geneticists toward the profession.

Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed a more nuanced picture, suggesting that CHIP may confer only a modest rise in myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors that modulate the pathological effects of CHIP.

Disability progression is a question of definition-A methodological reappraisal by example of primary progressive multiple sclerosis.

Background: Different definitions of disability progression by Expanded Disability Status Scale (EDSS) may influence frequency and/or time to event.

Methods: In this multicenter cohort study, we included PPMS patients with follow-up ≥24 months and ≥3 available EDSS scores overall (≥1 per year). We applied 672 definitions of disability progression including different minimal EDSS increase, required confirmation and fixed/roving-baseline score.

Resilience and emergence of pneumococcal serotypes and lineages in adults post-PCV13 in Spain: A multicentre study.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain.

Bovine fecal biomarkers of intestinal inflammatory process: Calprotectin and lactoferrin, a comparative study.

Fecal lactoferrin and fecal calprotectin have been proposed as biomarkers of intestinal inflammation in several animal species. The main objectives of this work were to validate an analytical procedure for the measurement of lactoferrin in calf feces, to study the correlation between lactoferrin and calprotectin concentrations, and to evaluate the influence of fecal water content in the determination of these proteins. This knowledge is essential for effectively using these biomarkers in young calves exposed to inflammatory gastrointestinal diseases.

New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?

The classical BCR::ABL-negative myeloproliferative neoplasms (MPN) include Polycythemia Vera (PV), Essential Thrombocytemia (ET), and Primary Myelofibrosis (PMF). They are acquired clonal disorders of the hematopoietic stem cells (HSC) leading to hyperplasia of one or several myeloid lineages. MPN are caused by three main recurrent mutations, JAK2V617F and mutations in the calreticulin (CALR) and the thrombopoietin receptor (MPL) genes.

Direct analysis by ultra-high-resolution mass spectrometry of lipid A and phospholipids from Acinetobacter baumannii cells.

Acinetobacter baumannii, classified as priority number one by the World Health Organization (WHO), is an opportunistic pathogen responsible for infection and is able to develop antibiotic resistance easily. Membranes are bacteria's first line of defense against external aggression, such as antibiotics. A chemical modification of a lipid family or a change in lipid composition can lead to resistance to antibiotics.

Chlorine dioxide may be an alternative to acidification and chlorination for drinking water chemical disinfection in dairy beef bulls.

Alternative water disinfectants to chlorination need to be identified because its effectiveness is limited by water pH and potentially carcinogen by-products resulted from chlorination and organic compound reaction. The first study aimed to evaluate the effect of different drinking water chemical disinfection treatments on water quality, its potential hazard effects on animal health, water and feed consumption, and apparent total tract digestibility in dairy beef bulls fed high-concentrate diets. For 224 days, 24 Holstein bulls (176 ± 16.

Insights into the recognition of hypermucoviscous clinical isolates by innate immune lectins of the Siglec and galectin families.

is an opportunistic bacterium that frequently colonizes the nasopharynx and gastrointestinal tract and can also cause severe infections when invading other tissues, particularly in immunocompromised individuals. Moreover, variants exhibiting a hypermucoviscous (HMV) phenotype are usually associated with hypervirulent strains that can produce invasive infections even in immunocompetent individuals. Major carbohydrate structures displayed on the surface are the polysaccharide capsule and the lipopolysaccharide, which presents an O-polysaccharide chain in its outermost part.

Molecular characterization of macrolide resistance in Haemophilus influenzae and Haemophilus parainfluenzae strains (2018-21).

Objectives: This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (n = 2556) and Haemophilus parainfluenzae (n = 510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain.

Methods: Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures.

Formulation and dermal delivery of a new active pharmaceutical ingredient in an in vitro wound model for the treatment of chronic ulcers.

The aim of this study was to investigate dermal delivery of the new active pharmaceutical ingredient (API) TOP-N53 into diabetic foot ulcer using an in vitro wound model consisting of pig ear dermis and elucidate the impact of drug formulation and wound dressing taking into consideration clinical relevance in the home care setting and possible bacterial infection. Different formulation approaches for the poorly water-soluble API including colloidal solubilization, drug micro-suspension and cosolvent addition were investigated; moreover, the effect of (micro-)viscosity of hydrogels used as primary wound dressing on delivery was assessed. Addition of Transcutol® P as cosolvent to water improved solubility and was significantly superior to all other approaches providing a sustained three-day delivery that reached therapeutic drug levels in the tissue.

Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: transmission dynamics and epidemiological insights.

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants.

Materials And Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior.

Computational study of the mechanism of a polyurethane esterase A (PueA) from .

The effective management of plastic waste has become a global imperative, given our reliance on a linear model in which plastics are manufactured, used once, and then discarded. This has led to the pervasive accumulation of plastic debris in landfills and environmental contamination. Recognizing this issue, numerous initiatives are underway to address the environmental repercussions associated with plastic disposal.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study.

Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain.

Different lymphocyte counts of multiple sclerosis patients treated with ofatumumab and ocrelizumab: A retrospective observational study.

Introduction: Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA.

Objective: To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA.

Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

Background: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet.

Methods: This is a pilot prospective, double-blind randomized trial.

Sex differences in multiple sclerosis relapse presentation and outcome: a retrospective, monocentric study of 134 relapse events.

Background: Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses).

Objectives: A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3-6 months) as measured by Expanded Disability Status Scale (EDSS) change.

Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (M) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against M (K: 1-10 μM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC: 1-12 μM) without significant toxicity.

Imipenem heteroresistance but not tolerance in during chronic lung infection associated with chronic obstructive pulmonary disease.

Antibiotic resistance is a major Public Health challenge worldwide. Mechanisms other than resistance are described as contributors to therapeutic failure. These include heteroresistance and tolerance, which escape the standardized procedures used for antibiotic treatment decision-making as they do not involve changes in minimal inhibitory concentration (MIC).