The platelet-mitochondria nexus in autoimmune and musculoskeletal diseases.

Platelets are crucial for thrombosis and hemostasis. Importantly, they contain mitochondria that are responsible for energy generation and therefore vital for platelet survival and activation. Activated platelets can release mitochondria that may be free or encapsulated in platelet extracellular vesicles (EVs).

Testing the Influence of Tactics on an Intention to Participate in an Environmental Management Collaborative.

Complexity, uncertainty, and conflict characterize contemporary environmental challenges. Addressing these issues is beyond the purview of any one actor. A collaborative approach to environmental management is required; participation in collaboration is needed.

Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.

Current prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs.

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses.

A new method for quantifying Cu in nuclear debris samples.

Quantifying Cu in post-detonation nuclear debris samples can provide important diagnostic information regarding the structural materials used within a nuclear device. However, this task is challenging due to the weak gamma emissions associated with the decay of Cu, its short half-life (12.701 h), and the presence of interfering fission product radioisotopes.

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.

Background: The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.

Objectives: A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).

Methods: Eighty participants were randomized.

Test, evidence, transition projects in Scotland: developing the evidence needed for transition of effective interventions in cancer care from innovation into mainstream practice.

Background: A robust evidence base is required to assist healthcare commissioners and providers in selecting effective and sustainable approaches to improve cancer diagnosis and treatment. Such evidence can be difficult to build, given the fast-paced and highly pressured nature of healthcare delivery, the absence of incentives, and the presence of barriers in conducting pragmatic yet robust research evaluations. Cancer Research UK (CRUK) has played an active part in building the evidence base through its funding of programmes to identify, evaluate and scale-up innovative approaches across the UK.

A wild boar cathelicidin peptide derivative inhibits severe acute respiratory syndrome coronavirus-2 and its drifted variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress.

Farnesoid X receptor regulators from natural products and their biological function.

Metabolic syndrome (MetS) has been a growing public health concern worldwide without specific medicine. Through summarizing the chemical structure type and effect mechanisms of natural products targeted on farnesoid X receptor (FXR), to provide the research basis for exploring the treatment of MetS. The following databases were searched for natural products which targeting FXR: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, and Chinese Biomedical Literature Database.

Chemical separation and measurement of platinum activation products.

A method has been developed to purify and measure platinum radioisotopes in the presence of fission products and environmental constituents. The method uses a combination of cation exchange and anion exchange chromatography and selective precipitation steps to remove other radioisotopes from the sample. The addition of stable platinum carrier allows for a gravimetric determination of the chemical yield of the procedure.

Perioperative Management in the Collegiate Athlete: An Integrated Approach.

Collegiate athletes face rigorous physical, academic, and emotional demands. While significant attention has been paid to injury prevention among young athletes in the past two decades, orthopedic injury rates remain high among collegiate athletes, and a significant number will undergo surgical management for injuries each year. In this narrative review, we describe techniques for perioperative management of pain and stress after surgery in collegiate athletes.

Structure-activity relationships of actively FhuE transported rifabutin derivatives with potent activity against Acinetobacter baumannii.

Hospital-acquired infections are on the rise and represent both, a clinical and financial burden. With resistance emerging and an ever-dwindling armamentarium at hand, infections caused by Acinetobacter baumannii are particularly problematic, since these bacteria have a high level of resistance and resilience to traditional and even last-resort antibiotics. The antibiotic rifabutin was recently found to show potent in vitro and in vivo activity against extensively drug resistant A.

Comparative metabolism and tolerability of racemic primaquine and its enantiomers in human volunteers during 7-day administration.

Primaquine (PQ) is an 8-aminoquinoline antimalarial, active against dormant hypnozoites and mature gametocytes. PQ is currently used for radical cure and prevention of malaria transmission. PQ is a racemic drug and since the metabolism and pharmacology of PQ's enantiomers have been shown to be divergent, the objectives of this study were to evaluate the comparative tolerability and metabolism of PQ with respect to its two enantiomers in human volunteers in a 7 days' treatment schedule.

Use of crowdsourced images for determining 2D:4D and relationship to pro-environmental variables.

Unlabelled: The primary purpose of this study was to examine whether 2D:4D ratios (a putative measure of prenatal androgen exposure) could be determined using participant-submitted hand images. The secondary purpose was to examine whether 2D:4D ratio was associated with pro-environmental behaviors, attitudes, and empathy, given the recent literature linking sex to environmental attitudes and actions. Participants ( = 1065) were asked via an online survey to submit a clear photograph of their right hand, palm side up.

Comparative single dose pharmacokinetics and metabolism of racemic primaquine and its enantiomers in human volunteers.

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity.

Design and synthesis of water-soluble prodrugs of rifabutin for intraveneous administration.

Acinetobacter baumannii is a gram-negative bacterium causing severe hospital-acquired infections such as bloodstream infections or pneumonia. Moreover, multidrug resistant A. baumannii becomes prevalent in many hospitals.

Somatic Diversification of Rearranged Antibody Gene Segments by Intra- and Interchromosomal Templated Mutagenesis.

The ability of the humoral immune system to generate Abs capable of specifically binding a myriad of Ags is critically dependent on the somatic hypermutation program. This program induces both templated mutations (i.e.

A Patient With Sepsis-Induced Multiorgan Failure and Increasing Serum Methadone Concentration: A Case Study.

The authors describe a patient with substance use disorder admitted to the hospital with septic shock and multiorgan failure, in whom the serum concentration of methadone kept increasing despite discontinuation of the drug. Therapeutic drug monitoring was performed to monitor the methadone serum concentration during treatment of the underlying diseases.

Oxazepam Detected in Urine 79 Days After Withdrawal of Diazepam: A Case Report.

Patients suffering from substance use disorder, including for instance benzodiazepines, may have comorbidity with attention deficit hyperactivity disorder (ADHD). Centrally acting stimulants play an important role in the treatment of ADHD. Before such treatment can be initiated, withdrawal of benzodiazepines may be necessary.

Evaluating ecological outcomes from environmental stewardship initiatives: A comparative analysis of approaches.

Understanding the extent to which stewardship initiatives achieve objectives of enhanced ecological outcomes is important for enhancing effectiveness and efficiency of environmental management initiatives. Alternative approaches - community science, stakeholder perceptions, and remote sensing - are emerging in lieu of the conventional approach of collecting field data that present different benefits and drawbacks and to date have not been directly compared. This research compared the use of four approaches to evaluating ecological outcomes of a grassland restoration project on a 2 ha Niagara Parks Commission property in Ontario, Canada.

Rifabutin for infusion (BV100) for the treatment of severe carbapenem-resistant Acinetobacter baumannii infections.

Rifamycin antibiotics were discovered during the 1950s, and their main representative, rifampicin, remains a cornerstone treatment for TB. The clinical use of rifamycin is restricted to mycobacteria and Gram-positive infections because of its poor ability to penetrate the Gram-negative outer membrane. Rifabutin, a rifamycin antibiotic approved for the prevention of Mycobacterium avium complex disease, makes an exception to this rule by hijacking the iron uptake system of Acinetobacter baumannii, resulting in potent activity against this important Gram-negative pathogen.

Increased procoagulant platelet levels are predictive of death in COVID-19.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death.

Individual difference predictors of learning and generalization in perceptual learning.

Given appropriate training, human observers typically demonstrate clear improvements in performance on perceptual tasks. However, the benefits of training frequently fail to generalize to other tasks, even those that appear similar to the trained task. A great deal of research has focused on the training task characteristics that influence the extent to which learning generalizes.

Review of Clinical Questions Submitted to Norwegian Drug Information Centres Concerning Administration and Dosage to Older Patients of Relevance to Patient-Centric Care.

Patient-centric care entails optimising healthcare provision to patients based on their perspective and opinion. It involves appropriate treatment at a reasonable cost and a focus on patient characteristics in the decision-making process to make it more personally useful. The optimisation of medicines in the older population is a challenge due to physiological changes, comorbidity, and polypharmacy.

The amphibian peptide Yodha is virucidal for Zika and dengue viruses.

Zika virus (ZIKV) has emerged as a serious health threat in the Americas and the Caribbean. ZIKV is transmitted by the bite of an infected mosquito, sexual contact, and blood transfusion. ZIKV can also be transmitted to the developing fetus in utero, in some cases resulting in spontaneous abortion, fetal brain abnormalities, and microcephaly.