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Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia.
Get PDFMitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1-3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline
Secondary stroke prevention in people with atrial fibrillation: treatments and trials.
No full textAtrial fibrillation is one of the most common cardiac arrhythmias and is a major cause of ischaemic stroke. Recent findings indicate the importance of atrial fibrillation burden (device-detected, subclinical, or paroxysmal and persistent or permanent) and whether atrial fibrillation was known before stroke onset or diagnosed after stroke for the risk of recurrence. Secondary prevention in patients with atrial fibrillation and stroke aims to reduce the risk of recurrent ischaemic stroke. Findings from randomised controlled trials assessing the optimal timing to introduce direct oral anticoagulant therapy after a stroke show that early start (ie, within 48 h for minor to moderate strokes and within 4-5 days for large strokes) seems safe and could reduce the risk of early recurrence. Other promising developments regarding early rhythm control, left atrial appendage occlusion, and novel factor XI inhibitor oral anticoagulants suggest that these therapies have the potential to further reduce the risk of stroke. Secondary prevention strategies in patients with atrial fibrillation who have a stroke despite oral anticoagulation therapy is an unmet medical need. Research advances suggest a heterogeneous spectrum of causes, and ongoing trials are investigating new approaches for secondary prevention in this vulnerable patient group. In patients with atrial fibrillation and a history of intracerebral haemorrhage, the latest data from randomised controlled trials on stroke prevention shows that oral anticoagulation reduces the risk of ischaemic stroke but more data are needed to define the safety profile
Lacustrine rhythmites from the Mulhouse Basin (Upper Rhine Graben, France): a sedimentary record of increased seasonal climatic contrast and sensitivity of the climate to orbital variations through the Eocene-Oligocene Transition
Get PDFCommentary: Clinical characteristics of male prolactinoma patients mainly presenting with severe obesity and the metabolic response to dopamine agonist therapy.
Get PDFRoot-exuded specialized metabolites reduce arsenic toxicity in maize.
Get PDFBy releasing specialized metabolites, plants modify their environment. Whether and how specialized metabolites protect plants against toxic levels of trace elements is not well understood. We evaluated whether benzoxazinoids, which are released into the soil by major cereals, can confer protection against arsenic toxicity. Benzoxazinoid-producing maize plants performed better in arsenic-contaminated soils than benzoxazinoid-deficient mutants in the greenhouse and the field. Adding benzoxazinoids to the soil restored the protective effect, and the effect persisted to the next crop generation via positive plant-soil feedback. Arsenate levels in the soil and total arsenic levels in the roots were lower in the presence of benzoxazinoids. Thus, the protective effect of benzoxazinoids is likely soil-mediated and includes changes in soil arsenic speciation and root accumulation. We conclude that exuded specialized metabolites can enhance protection against toxic trace elements via soil-mediated processes and may thereby stabilize crop productivity in polluted agroecosystems
Proof-of-concept evidence for high-density EEG investigation of sleep slow wave traveling in First-Episode Psychosis.
Get PDFSchizophrenia is thought to reflect aberrant connectivity within cortico-cortical and reentrant thalamo-cortical loops, which physiologically integrate and coordinate the function of multiple cortical and subcortical structures. Despite extensive research, reliable biomarkers of such "dys-connectivity" remain to be identified at the onset of psychosis, and before exposure to antipsychotic drugs. Because slow waves travel across the brain during sleep, they represent an ideal paradigm to study pathological conditions affecting brain connectivity. Here, we provide proof-of-concept evidence for a novel approach to investigate slow wave traveling properties in First-Episode Psychosis (FEP) with high-density electroencephalography (EEG). Whole-night sleep recordings of 5 drug-naïve FEP and 5 age- and gender-matched healthy control subjects were obtained with a 256-channel EEG system. One patient was re-recorded after 6 months and 3 years of continuous clozapine treatment. Slow wave detection and traveling properties were obtained with an open-source toolbox. Slow wave density and slow wave traveled distance (measured as the line of longest displacement) were significantly lower in patients (p < 0.05). In the patient who was tested longitudinally during effective clozapine treatment, slow wave density normalized, while traveling distance only partially recovered. These preliminary findings suggest that slow wave traveling could be employed in larger samples to detect cortical "dys-connectivity" at psychosis onset
Meaning in elite sport – A narrative review of scholarship in sport psychology
No full textAthletes’ heart-felt stories about their experiences in elite sport almost naturally evoke the notion of meaning. However, although various scholars and practitioners have suggested the concept of meaning to the sport psychology audience in the past two decades (e.g., Beckmann, 2023; Ravizza, 2002; Ronkainen & Nesti, 2020), its study in this discipline is still in the early stages compared to established psychological scholarship on the topic. To promote meaning as a complementary lens for research and applied work in sport psychology, the presentation aims to introduce the concept informed by psychological inquiry, and to synthesize and critically comment on the extant scholarship. For this, the wider meaning in life literature will be drawn on to give an overview of components, sources, pathways, and qualities of meaning and set it apart from the related concept of purpose
Standardisation of Definition and Management for Bleeding Disorder of Unknown Cause: Communication from the SSC of the ISTH.
No full textIn many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practise with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the ISTH bleeding assessment tool (BAT). Patients with increased BAT scores should progress to hemostasis laboratory testing. To diagnose BDUC, normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function; coagulation factors VIII, IX and XI and platelet light transmission aggregometry (LTA) should be the minimum laboratory assessment. In some laboratories, additional specialized haemostasis testing may be performed and identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of 'Bleeding disorder of unknown cause (BDUC)' in preference to other terminology. Global haemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin and platelet transfusions
Observational longitudinal study on Toxoplasma gondii infection in fattening beef cattle: serology and associated haematological findings.
Get PDFToxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is a globally distributed zoonotic infection with significant implications for human and animal health. This study investigated the prevalence of T. gondii infection in a population of beef cattle at three different stages of their productive lifespan and examined the impact of T. gondii serological status on blood parameters. A commercial beef fattening unit in Italy was the setting for this research, which involved a biosecurity assessment upon cattle arrival, blood sampling at three time points and Toxoplasma-specific serological testing using indirect fluorescent antibody tests (IFAT). Results revealed a dynamic pattern of T. gondii seropositivity in cattle, with an initial prevalence of 30.6% at arrival (T0) that increased to 44.6% at 14 days (T1) and then decreased slightly to 39.3% at slaughter after 5 months (T2). Interestingly, seroconversion was observed during the study, indicating ongoing infections, and antibody waning occurred in some animals. In terms of blood parameters, seropositive cattle exhibited significantly lower mean corpuscular volume (MCV) and a higher neutrophil-lymphocyte (N/L) ratio, suggesting an activation of the innate immune response. Furthermore, cattle with higher antibody titres displayed higher neutrophil counts. However, all blood parameters with a statistical significance were within the reference range. This study provides for the first time a longitudinal investigation on the serological status for T. gondii in naturally exposed beef cattle. These findings provide valuable insights into the clinico-pathological aspects of natural T. gondii exposure in cattle and underscore the importance of monitoring and managing T. gondii infection in livestock production systems
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