The Cardioprotective Effects of Nutritional Ketosis: Mechanisms and Clinical Implications.

Cardiovascular diseases (CVDs) persist as the primary cause of death worldwide, accounting for roughly 17.9 million fatalities each year. The prevalence of obesity, metabolic syndrome, and type 2 diabetes (key risk factors for CVD) continues to escalate at an alarming rate, necessitating novel therapeutic strategies to address this global health crisis.

SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections.

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection.

HerpesDRG: a comprehensive resource for human herpesvirus antiviral drug resistance genotyping.

The prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. Currently no single database cataloguing resistance mutations exists, which hampers the use of sequence data for patient management. We therefore developed HerpesDRG, a drug resistance mutation database that incorporates all the known resistance genes and current treatment options, built from a systematic review of available genotype to phenotype literature.

Using a human colonoid-derived monolayer to study bacteriophage translocation.

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation , we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment .

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.

Background: Human cytomegalovirus (HCMV) is the most common and serious opportunistic infection after solid organ and hematopoietic stem cell transplantation. In this study, we used whole-genome HCMV data to investigate viral factors associated with the clinical outcome.

Methods: We sequenced HCMV samples from 16 immunocompromised pediatric patients with persistent viremia.

Use of Bacteriophages to Target Intracellular Pathogens.

Bacteriophages (phages) have shown great potential as natural antimicrobials against extracellular pathogens (eg, Escherichia coli or Klebsiella pneumoniae), but little is known about how they interact with intracellular targets (eg, Shigella spp., Salmonella spp., Mycobacterium spp.

Antiulcer activity and mechanism of action of the hydroethanolic extract of leaves of Terminalia argentea Mart. In different in vivo and in vitro experimental models.

Ethnopharmacological Relevance: Terminalia argentea Mart. (Combretaceae) is a deciduous tree commonly found in Brazil, Bolivia, and Paraguay. It occurs in all regions of Brazil and is widespread in the Amazon, Cerrado, Pantanal, Atlantic Rain Forest, and Caatinga Biomes.

Genomic and geographical structure of human cytomegalovirus.

Human cytomegalovirus (CMV) has infected humans since the origin of our species and currently infects most of the world's population. Variability between CMV genomes is the highest of any human herpesvirus, yet large portions of the genome are conserved. Here, we show that the genome encodes 74 regions of relatively high variability each with 2 to 8 alleles.

A multi-scale clutch model for adhesion complex mechanics.

Cell-matrix adhesion is a central mechanical function to a large number of phenomena in physiology and disease, including morphogenesis, wound healing, and tumor cell invasion. Today, how single cells respond to different extracellular cues has been comprehensively studied. However, how the mechanical behavior of the main individual molecules that form an adhesion complex cooperatively responds to force within the adhesion complex is still poorly understood.

Positive, negative and controlled durotaxis.

Cell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration, and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science.

Cold temperature stress and damaged skin induced high mortality in barramundi (Lates calcarifer) challenged with Vibrio harveyi.

Most diseases in aquaculture are caused by opportunistic pathogens. One of them, Vibrio harveyi, is a widespread Gram-negative bacterium that has become an important pathogen of aquatic species in marine environments. Here, we propose the use of the causal pie model as a framework to conceptualize the causation of vibriosis in juvenile barramundi (Lates calcarifer) and to establish an effective challenge model.

Multidisciplinary Assessment and Individualized Nutritional Management of Dysphagia in Older Outpatients.

Introduction: The evidence on the efficacy of nutrition therapy to prevent complications of dysphagia is based on observational studies that used different tools for nutritional and dysphagia assessment, and different scales for the definition of diet textures, rendering their results incomparable and the knowledge on dysphagia management inconclusive.

Methods: This retrospective observational study was performed in 267 older outpatients who were assessed for dysphagia and nutritional status by a multidisciplinary team at the Clinical Nutrition Unit of IRCCS INRCA geriatric research hospital (Ancona, Italy) from 2018 to 2021. GUSS test and ASHA-NOMS measurement systems were used for dysphagia assessment, GLIM criteria for the assessment of nutritional status, and the IDDSI framework to describe the texture-modified diets.

Physical frailty, activity limitation and mortality in older Brazilians: longitudinal findings from FIBRA-BH study (2009-2019).

The aim was to investigate the longitudinal association between physical frailty and change in the profile of limitation to perform basic and instrumental activities of daily living (BADL and IADL) and mortality in a 10-year period in Brazilian community-dwelling older people. A longitudinal study was conducted with data from the Frailty in Brazilian Older People (FIBRA) study, 2009-2019. Physical frailty was categorized into vulnerability (pre-frail and frail) and robustness (non-frail).

L-Form Switching in Escherichia coli as a Common β-Lactam Resistance Mechanism.

Cell wall deficient bacterial L-forms are induced by exposure to cell wall-targeting antibiotics and immune effectors such as lysozyme. L-forms of different bacteria (including Escherichia coli) have been reported in human infections, but whether this is a normal adaptive strategy or simply an artifact of antibiotic treatment in certain bacterial species remains unclear. Here we show that members of a representative, diverse set of pathogenic E.

Pericyte derived chemokines amplify neutrophil recruitment across the cerebrovascular endothelial barrier.

Excessive neutrophil extravasation can drive immunopathology, exemplified in pyogenic meningitis caused by infection. Insufficient knowledge of the mechanisms that amplify neutrophil extravasation has limited innovation in therapeutic targeting of neutrophil mediated pathology. Attention has focussed on neutrophil interactions with endothelia, but data from mouse models also point to a role for the underlying pericyte layer, as well as perivascular macrophages, the only other cell type found within the perivascular space in the cerebral microvasculature.

Biological foundations of successful bacteriophage therapy.

Bacteriophages (phages) are selective viral predators of bacteria. Abundant and ubiquitous in nature, phages can be used to treat bacterial infections (phage therapy), including refractory infections and those resistant to antibiotics. However, despite an abundance of anecdotal evidence of efficacy, significant hurdles remain before routine implementation of phage therapy into medical practice, including a dearth of robust clinical trial data.

Co-Occurrence of Multidrug Resistant Klebsiella pneumoniae Pathogenic Clones of Human Relevance in an Equine Pneumonia Case.

The global epidemiology of multidrug resistant Klebsiella pneumoniae, a serious threat to both animal and human health, is dominated by the spread of pathogenic clones, each separately evolving via acquisition of transferable antibiotic resistance or niche-specific virulence determinants. In horses, K. pneumoniae infection can lead to severe respiratory illness.

Can Social Resources Explain the Limitations in the Activities of Daily Living of Older Adults Classified by the Phenotype of Physical Frailty?

The objective is to investigate the mediating roles of living alone and personal network in the relationship between physical frailty and activities of daily living (ADL) limitations among older adults. 2271 individuals were classified as vulnerable (pre-frail or frail) or robust. Mediating variables were living alone and personal network.