A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

Process of development of decentralised clinical trial methodology for cancer clinical trials in Aotearoa New Zealand.

Aim: To develop processes for the development of decentralised clinical trial methodology for Aotearoa New Zealand, focussing on equity of access to cancer clinical trials for Māori, Pacific people, vulnerable communities and those in rural settings.

Methods: A national steering committee supported by Te Aho o Te Kahu - Cancer Control Agency was formed to: guide the adaptation and implementation of overseas decentralised clinical trial models to suit the needs of Aotearoa New Zealand with an equity focus; provide high-level oversight and expertise for direction and development of policies, procedures and infrastructure compliant with ICH GCP R2; and implement a national strategy.

Results: Twelve standard operating procedures were developed, as well as a supervision plan and a glossary.

Microsporidia and invertebrate hosts: genome-informed taxonomy surrounding a new lineage of crayfish-infecting spp. (Nosematida).

The Microsporidia, an often overlooked fungal lineage, exhibit increasing diversity and taxonomic understanding with the use of genomic techniques. They are obligate parasites infecting a diversity of hosts, including crustaceans. Crustacea are, in essence, ancient insects and their relationship with the Microsporidia is both diverse and convoluted.

Barriers and facilitators to designing, maintaining, and utilizing rare disease patient registries: a scoping review protocol.

Objective: The objectives of this review are to identify barriers/facilitators to designing, maintaining, and utilizing rare disease patient registries (RDPRs); determine whether and how these differ among patient partners, other knowledge users (KUs), and researchers; and chart definitions of rare diseases and RDPRs.

Introduction: RDPRs are vital to improving the understanding of the natural histories and predictors of outcomes for rare diseases, assessing interventions, and identifying potential participants for clinical trials. Currently, however, the functionality of RDPRs is not fully optimized.

Intercropping Alters Phytochemical Defenses Against Insect Herbivory.

Given the multiple possible mechanisms for interspecific chemical interaction between adjacent heterospecific plants, phytochemical defenses of pest-susceptible crop species could potentially be enhanced or altered by intercropping with phytochemically diverse neighbors. We assessed the influence of intercropping between phytochemically diverse plants on aerial volatile organic compound (VOC) emission profiles by intercropping and Triticum with in AMF-inoculated soil. We also assessed the impact of intercropping on induced plant defenses by conducting an in-situ, no-choice bioassay with .

North American crayfish harbour diverse members of the Nudiviridae.

Three novel crayfish-infecting nudiviruses from crayfish in North America represent the first genomic confirmation of nudiviruses in crayfish: Faxonius propinquus nudivirus (FpNV), Faxonius rusticus nudivirus (FrNV), and Faxonius virilis nudivirus (FvNV). Histopathology and electron microscopy revealed nuclear infections, including nuclear hypertrophy in hepatopancreatic epithelial cells and the presence of membrane-bound bacilliform virions. Metagenomic sequencing resulted in complete circular genome assembly, and phylogenetic analyses (based on nudivirus core genes) placed these viruses within the unofficial Epsilonnudivirus genus.

uafR: An R package that automates mass spectrometry data processing.

Chemical information has become increasingly ubiquitous and has outstripped the pace of analysis and interpretation. We have developed an R package, uafR, that automates a grueling retrieval process for gas -chromatography coupled mass spectrometry (GC -MS) data and allows anyone interested in chemical comparisons to quickly perform advanced structural similarity matches. Our streamlined cheminformatics workflows allow anyone with basic experience in R to pull out component areas for tentative compound identifications using the best published understanding of molecules across samples (pubchem.

Ureidopenicillins Are Potent Inhibitors of Penicillin-Binding Protein 2 from Multidrug-Resistant H041.

Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses.

An interdisciplinary course on computer-aided drug discovery to broaden student participation in original scientific research.

We present a new highly interdisciplinary project-based course in computer aided drug discovery (CADD). This course was developed in response to a call for alternative pedagogical approaches during the COVID-19 pandemic, which caused the cancellation of a face-to-face summer research program sponsored by the Louisiana Biomedical Research Network (LBRN). The course integrates guided research and educational experiences for chemistry, biology, and computer science students.

Safeguarding strategies in athletes with intellectual disabilities: A narrative review.

Compared to their non-disabled peers, athletes with disabilities are at an increased risk of interpersonal violence in sport. Athletes with intellectual disabilities specifically may face compounded risk due to impaired communication and social challenges. Despite the inherent risk of interpersonal violence in athletes with intellectual disabilities, there is a paucity of literature focused on safeguarding strategies in this population, and no global consensus prevention guidelines exist.

Development of a physical activity counseling intervention for people with chronic respiratory disease based on the health action process approach.

Background: Physical activity (PA) counseling holds promise for increasing PA levels in people with chronic respiratory disease, though little long-term change has been shown to date. Here, we describe the development of a Health Action Process Approach-based PA counseling intervention that aims to promote PA and exercise in people with chronic respiratory disease who are enrolled in pulmonary rehabilitation.

Methods: To collaborate in defining and refining the intervention, we convened a varied team of authors that included a panel of five stakeholder partners: three patients, one clinician, and one health behavior change researcher.

Interim guidelines for the assessment and treatment of pain in children with multiple sclerosis.

Introduction: Pain in multiple sclerosis (MS) is common, but literature on pain in children with MS remains scarce. Pain has physical, psychological, and social implications in MS, and both comprehensive assessment and interdisciplinary management approaches are needed. We sought to develop an interdisciplinary interim guideline for the assessment and management of pain in children with MS.

Discovery of a novel transcriptional regulator of sugar catabolism in archaea.

The haloarchaeon Haloferax volcanii degrades D-glucose via the semiphosphorylative Entner-Doudoroff pathway and D-fructose via a modified Embden-Meyerhof pathway. Here, we report the identification of GfcR, a novel type of transcriptional regulator that functions as an activator of both D-glucose and D-fructose catabolism. We find that in the presence of D-glucose, GfcR activates gluconate dehydratase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase and also acts as activator of the phosphotransferase system and of fructose-1,6-bisphosphate aldolase, which are involved in uptake and degradation of D-fructose.

Cambaraspora faxoni n. sp. (Microsporidia: Glugeida) from native and invasive crayfish in the USA and a novel host of Cambaraspora floridanus.

Crayfishes are among the most widely introduced freshwater taxa and can have extensive ecological impacts. Knowledge of the parasites crayfish harbor is limited, yet co-invasion of parasites is a significant risk associated with invasions. In this study, we describe a novel microsporidium, Cambaraspora faxoni n.

Alternosema astaquatica n. sp. (Microsporidia: Enterocytozoonida), a systemic parasite of the crayfish Faxonius virilis.

Crayfish have strong ecological impacts in freshwater systems, yet our knowledge of their parasites is limited. This study describes the first systemic microsporidium (infects multiple tissue types) Alternosema astaquatica n. sp.

Changes to physical activity behavior during the COVID-19 pandemic and their associated factors: a cross sectional survey of Mexican women.

Background: On March 24, 2020, the Mexican Government established social distancing measures to address the outbreak of the COVID-19 pandemic. The resulting home confinement affected daily lifestyle habits such as eating, sleeping, and physical activity (PA). The objectives of this study were to determine changes in PA behaviors among Mexican women due to the COVID-19 pandemic and to assess potential factors associated with these changes.

Genotype accounts for intraspecific variation in the timing and duration of multiple, sequential life-cycle events in a willow species.

Premise: Phenological variation among individuals within populations is common and has a variety of ecological and evolutionary consequences, including forming the basis for population-level responses to environmental change. Although the timing of life-cycle events has genetic underpinnings, whether intraspecific variation in the duration of life-cycle events reflects genetic differences among individuals is poorly understood.

Methods: We used a common garden experiment with 10 genotypes of Salix hookeriana (coastal willow) from northern California, United States to investigate the extent to which genetic variation explains intraspecific variation in the timing and duration of multiple, sequential life-cycle events: flowering, leaf budbreak, leaf expansion, fruiting, and fall leaf coloration.

The "STOP Pain" Questionnaire: using the Plan-Do-Study-Act model to implement a patient-family preferences-informed questionnaire into a pediatric transitional pain clinic.

Background: Patient engagement is an important tool for quality improvement (QI) and optimizing the uptake of research findings. The Plan-Do-Study-Act (PDSA) model is a QI tool that encourages ongoing evaluation of clinical care, thus improving various aspects of patient care. Ascertaining pediatric patient priorities for a pain questionnaire in the post-acute, or transitional pain, setting is important to guide clinical care since active engagement with the population of interest can optimize uptake.

Blind sports' blind spot: The global epidemiology of visual impairment against participation trends in elite blind para sport.

It remains unknown whether access to elite blind sports opportunities is globally balanced or matches the prevalence of blindness/visual impairment (VI). The primary objective of this study was to determine the rate of elite blind sports participation in each world region registered in the International Blind Sports Federation's (IBSA) and to assess its association with the global and regional prevalence of blindness/VI. The secondary objective was to determine the association between other covariates, such as age, vision class, and sex, with the number of IBSA-registered athletes from each region.

Nutrition vs association: plant defenses are altered by arbuscular mycorrhizal fungi association not by nutritional provisioning alone.

Background: While it is known that arbuscular mycorrhizal fungi (AMF) can improve nutrient acquisition and herbivore resistance in crops, the mechanisms by which AMF influence plant defense remain unknown. Plants respond to herbivory with a cascade of gene expression and phytochemical biosynthesis. Given that the production of defensive phytochemicals requires nutrients, a commonly invoked hypothesis is that the improvement to plant defense when grown with AMF is simply due to an increased availability of nutrients.

Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions.

Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms.

Forty Years of Molecular Diagnostics for Infectious Diseases.

Nearly 40 years have elapsed since the invention of the PCR, with its extremely sensitive and specific ability to detect nucleic acids via enzyme-mediated amplification. In turn, more than 2 years have passed since the onset of the coronavirus disease 2019 (COVID-19) pandemic, during which time molecular diagnostics for infectious diseases have assumed a larger global role than ever before. In this context, we review broadly the progression of molecular techniques in clinical microbiology, to their current prominence.

The Impact of the COVID-19 Pandemic on Healthy Lifestyle Behaviors and Perceived Mental and Physical Health of People Living with Non-Communicable Diseases: An International Cross-Sectional Survey.

The huge burden and vulnerability imposed by non-communicable diseases (NCDs) during the COVID-19 pandemic highlighted how healthy lifestyle behaviors and the well-being of people living with NCDs need to be prioritized. The aim of our study is to better understand the impact of the COVID-19 pandemic on healthy lifestyle behaviors and perceived mental and physical health among adults living with NCDs, as compared to people without NCDs. We conducted a cross-sectional study using a global online survey through Qualtrics.

Impact of the COVID-19 Pandemic on the Perceived Physical and Mental Health and Healthy Lifestyle Behaviors of People With Disabilities: A Quantitative Analysis of the International Community Survey.

Objective: This study aims to determine the perceived impact of the coronavirus pandemic on physical and mental health and healthy lifestyle behaviors in community-dwelling persons with disabilities, as compared with those without disabilities.

Design: A prospective cross-sectional study was conducted with a web-based global survey.

Results: Over 3 mos, 3550 responses were collected from 65 countries.