The evolution of diverse antimicrobial responses in vancomycin-intermediate Staphylococcus aureus and its therapeutic implications.

Staphylococcus aureus causes endocarditis, osteomyelitis, and bacteremia. Clinicians often prescribe vancomycin as an empiric therapy to account for methicillin-resistant S. aureus (MRSA) and narrow treatment based on culture susceptibility results. However, these results reflect a single time point before empiric treatment and represent a limited subset of the total bacterial population within the patient. Thus, while they may indicate that the infection is susceptible to a particular drug, this recommendation may no longer be accurate during therapy. Here, we addressed how antibiotic susceptibility changes over time by accounting for evolution. We evolved 18 methicillin-susceptible S. aureus (MSSA) populations under increasing vancomycin concentrations until they reached intermediate resistance levels. Sequencing revealed parallel mutations that affect cell membrane stress response and cell-wall biosynthesis. The populations exhibited repeated cross-resistance to daptomycin and varied responses to meropenem, gentamicin, and nafcillin. We accounted for this variability by deriving likelihood estimates that express a population's probability of exhibiting a drug response following vancomycin treatment. Our results suggest antistaphylococcal penicillins are preferable first-line treatments for MSSA infections but also highlight the inherent uncertainty that evolution poses to effective therapies. Infections may take varied evolutionary paths; therefore, considering evolution as a probabilistic process should inform our therapeutic choices.

Developmental change in predictive motor abilities.

Prediction is critical for successful interactions with a dynamic environment. To test the development of predictive processes over the life span, we designed a suite of interceptive tasks implemented as interactive video games. Four tasks involving interactions with a flying ball with titrated challenge quantified spatiotemporal aspects of prediction. For comparison, reaction time was assessed in a matching task. The experiments were conducted in a museum, where over 400 visitors across all ages participated, and in a laboratory with a focused age group. Results consistently showed that predictive ability improved with age to reach adult level by age 12. In contrast, reaction time continued to decrease into late adolescence. Inter-task correlations revealed that the tasks tested different aspects of predictive processes. This developmental progression complements recent findings on cerebellar and cortical maturation. Additionally, these results can serve as normative data to study predictive processes in individuals with neurodevelopmental conditions.

A low-cost, open-source evolutionary bioreactor and its educational use.

A morbidostat is a bioreactor that uses antibiotics to control the growth of bacteria, making it well-suited for studying the evolution of antibiotic resistance. However, morbidostats are often too expensive to be used in educational settings. Here we present a low-cost morbidostat called the EVolutionary biorEactor (EVE) that can be built by students with minimal engineering and programming experience. We describe how we validated EVE in a real classroom setting by evolving replicate Escherichia coli populations under chloramphenicol challenge, thereby enabling students to learn about bacterial growth and antibiotic resistance.

Statistical practice and transparent reporting in the neurosciences: Preclinical motor behavioral experiments.

Longitudinal and behavioral preclinical animal studies generate complex data, which may not be well matched to statistical approaches common in this literature. Analyses that do not adequately account for complexity may result in overly optimistic study conclusions, with consequences for reproducibility and translational decision-making. Recent work interrogating methodological shortcomings in animal research has not yet comprehensively investigated statistical shortcomings in the analysis of complex longitudinal and behavioral data. To this end, the current cross-sectional meta-research study rigorously reviewed published mouse or rat controlled experiments for motor rehabilitation in three neurologic conditions to evaluate statistical choices and reporting. Medline via PubMed was queried in February 2020 for English-language articles published January 1, 2017- December 31, 2019. Included were articles that used rat or mouse models of stroke, Parkinson's disease, or traumatic brain injury, employed a therapeutic controlled experimental design to determine efficacy, and assessed at least one functional behavioral assessment or global evaluation of function. 241 articles from 99 journals were evaluated independently by a team of nine raters. Articles were assessed for statistical handling of non-independence, animal attrition, outliers, ordinal data, and multiplicity. Exploratory analyses evaluated whether transparency or statistical choices differed as a function of journal factors. A majority of articles failed to account for sources of non-independence in the data (74-93%) and/or did not analytically account for mid-treatment animal attrition (78%). Ordinal variables were often treated as continuous (37%), outliers were predominantly not mentioned (83%), and plots often concealed the distribution of the data (51%) Statistical choices and transparency did not differ with regards to journal rank or reporting requirements. Statistical misapplication can result in invalid experimental findings and inadequate reporting obscures errors. Clinician-scientists evaluating preclinical work for translational promise should be mindful of commonplace errors. Interventions are needed to improve statistical decision-making in preclinical behavioral neurosciences research.

Teaching spirituality to medical students: a systematic review.

PURPOSE: Though it has become increasingly clear that religion and spirituality are important aspects of whole patient care, little is known about how this topic is taught to medical students. This systematic review examined the structure of courses teaching spirituality to medical students and assessed their impact on reported student outcomes. METHODS: In October 2020, the authors conducted a systematic review of the literature from 1926 to 2020 to identify published articles describing medical school spirituality curricula. Included studies were English-language articles that described spirituality courses predominantly designed for medical students, specified a curricular structure, and evaluated outcomes of the course. The authors used the Medical Education Research Study Quality Instrument (MERSQI) to assess the quality of the included studies and summarized course structures, curricular content, and study outcomes. RESULTS: Nineteen publications of the 1889 reviewed met the inclusion criteria. These studies were of moderate quality (mean MERSQI = 9.9). The majority of curricula were taught in United States medical schools. Courses were evenly split between mandatory versus elective classes, with mandatory courses having a shorter duration and higher total student participation. Most studies with clear student outcome evaluation had a pre- and post-test design. Common themes throughout the curricula included teaching how to take a spiritual history, delineating differences between spirituality and religion, and experience shadowing chaplains interacting with patients. CONCLUSIONS: This broad systematic review of the literature revealed a small but growing number of studies describing specific course structure and curricula for teaching spirituality at the medical student level. For the most concise approach, one short, mandatory didactic session followed by application with standardized or hospital patients can be an effective method of introducing students to the importance of spirituality. Important topics to address include the differences between religion and spirituality, recognizing spiritual distress, how to take a spiritual history, and the relevance of spirituality to student well-being. Measured student outcomes should encompass behavioral changes during patient care in addition to changes in knowledge and attitudes. Suggested methods of evaluation include reflective writing and adding a standardized patient case in which the patient is in spiritual distress in an Objective Structured Clinical Examination (OSCE).

UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic.

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm-2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 µWcm-2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.

Gender Differences in Throwing Revisited: Sensorimotor Coordination in a Virtual Ball Aiming Task.

Numerous studies have demonstrated that boys throw balls faster, farther and more accurately than girls. This may be largely due to well-known anatomical and muscle-physiological differences that play a central role in overarm throwing. With the objective to understand the potential contribution of the equally essential coordinative aspects in throwing for this gender difference, this large cross-sectional study examined a simplified forearm throw that eliminated the requirements that give males an advantage.While the overall performance error indeed became similar in the age groups younger than 20 years and older than 50 years, it was attenuated for middle-aged individuals. The gender differences remained in individuals who reported no throwing experience, but females with throwing experience reached similar performance as males. Two fine-grained spatiotemporal metrics displayed similar age-dependent gender disparities: while overall, males showed better spatiotemporal coordination of the ball release, age group comparisons specified that it was particularly middle-aged females that made more timing errors and did not develop a noise-tolerant strategy as males did. As throwing experience did not explain this age-dependency, the results are discussed in the context of spatial abilities and video game experience, both more pronounced in males. In contrast, a measure of rhythmicity developed over successive throws only revealed weak gender differences, speaking to the fundamental tendency in humans to fall into rhythmic patterns. Only the youngest individuals between 5 and 9 years of age showed significantly less rhythmicity in their performance. This computational study was performed in a large cohort in the context of an outreach activity, demonstrating that robust quantitative measures can also be obtained in less controlled environments. The findings also alert that motor neuroscience may need to pay more attention to gender differences.