Acute Achilles tendon rupture: Skip the surgery?

Nonoperative management for acute Achilles tendon rupture results in patient-reported outcomes similar to surgery at 1 year-but higher rates of rerupture.

What BP target is appropriate for pregnant patients with mild chronic hypertension?

Active treatment to a lower blood pressure goal (< 140/90 mm Hg) can improve pregnancy outcomes without increasing maternal or fetal risk.

Lessons learned through the implementation of a rural longitudinal integrated clerkship at the University of Missouri-Columbia.

INTRODUCTION: Created in 1995, The University of Missouri School of Medicine's Rural Track Pipeline Program was designed to address physician shortages in rural Missouri through medical student participation in a series of clinical and non-clinical programs over the course of their medical training to influence graduates to choose rural practice. METHODS: To increase the likelihood of students choosing rural practice, a 46-week longitudinal integrated clerkship (LIC) was implemented at one of nine existing rural training sites. Over the course of the academic year, quantitative and qualitative data was collected to evaluate effectiveness of the curriculum and for quality improvement purposes. RESULTS: Data collection is in progress and includes student evaluation of the clerkship, faculty evaluations of students, student evaluations of faculty, student aggregate clerkship performance, and qualitative data from student and faculty debrief sessions. DISCUSSION: Based on data collected, changes are being made to the curriculum for the following academic year to enhance the student experience. The LIC will also be offered at an additional rural training site beginning in June of 2022, and then expanded to a third site in June of 2023. As each LIC is unique, our hope is our experience and lessons learned will help others in developing a LIC or improving an existing LIC.

Glycan Conformation in the Heavily Glycosylated Protein, CEACAM1.

Glycans attached to glycoproteins can contribute to stability, mediate interactions with other proteins, and initiate signal transduction. Glycan conformation, which is critical to these processes, is highly variable and often depicted as sampling a multitude of conformers. These conformers can be generated by molecular dynamics simulations, and more inclusively by accelerated molecular dynamics, as well as other extended sampling methods. However, experimental assessments of the contribution that various conformers make to a native ensemble are rare. Here, we use long-range pseudo-contact shifts (PCSs) of NMR resonances from an isotopically labeled glycoprotein to identify preferred conformations of its glycans. The N-terminal domain from human Carcinoembryonic Antigen Cell Adhesion Molecule 1, hCEACAM1-Ig1, was used as the model glycoprotein in this study. It has been engineered to include a lanthanide-ion-binding loop that generates PCSs, as well as a homogeneous set of three 13C-labeled N-glycans. Analysis of the PCSs indicates that preferred glycan conformers have extensive contacts with the protein surface. Factors leading to this preference appear to include interactions between N-acetyl methyls of GlcNAc residues and hydrophobic surface pockets on the protein surface.

In Vitro and In Vivo Properties of CUO246, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor.

CUO246, a novel DNA gyrase/topoisomerase IV inhibitor, is active in vitro against a broad range of Gram-positive, fastidious Gram-negative, and atypical bacterial pathogens and retains activity against quinolone-resistant strains in circulation. The frequency of selection for single step mutants of wild-type S. aureus with reduced susceptibility to CUO246 was <4.64 × 10-9 at 4× and 8× MIC and remained low when using an isogenic QRDR mutant (<5.24 × 10-9 at 4× and 8× MIC). Biochemical assays indicated that CUO246 had potent inhibitory activity against both DNA gyrase (GyrAB) and topoisomerase IV (ParCE). Furthermore, CUO246 showed rapid bactericidal activity in time-kill assays and potent in vivo efficacy against S. aureus in a neutropenic murine thigh infection model. These results suggest that CUO246 may be useful in treating infections by various causative agents of acute skin and skin structure infections, respiratory tract infections, and sexually transmitted infections.

AssignSLP_GUI, a software tool exploiting AI for NMR resonance assignment of sparsely labeled proteins.

Not all proteins are amenable to uniform isotopic labeling with 13C and 15N, something needed for the widely used, and largely deductive, triple resonance assignment process. Among them are proteins expressed in mammalian cell culture where native glycosylation can be maintained, and proper formation of disulfide bonds facilitated. Uniform labeling in mammalian cells is prohibitively expensive, but sparse labeling with one or a few isotopically enriched amino acid types is an option for these proteins. However, assignment then relies on accessing the best match between a variety of measured NMR parameters and predictions based on 3D structure, often from X-ray crystallography. Finding this match is a challenging process that has benefitted from many computational tools, including trained neural nets for chemical shift prediction, genetic algorithms for searches through a myriad of assignment possibilities, and now AI-based prediction of high-quality structures for protein targets. AssignSLP_GUI, a new version of a software package for assignment of resonances from sparsely-labeled proteins, uses many of these tools. These tools and new additions to the package are highlighted in an application to a sparsely-labeled domain from a glycoprotein, CEACAM1.

Can extended anticoagulation prophylaxis after discharge prevent thromboembolism?

A meta-analysis confirmed the benefit of thromboprophylaxis with a direct oral anticoagulant for high-risk nonsurgical patients after hospital discharge.

Validated scoring system identifies low-risk syncope patients.

This study validated the Canadian Syncope Risk Score for predicting 30-day serious outcomes in patients presenting to the ED within 24 hours of syncope.

This is not the time to modify a HTN regimen.

Intensifying hypertension regimens at discharge increases risk in older patients.

Using molecular dynamics trajectories to predict nuclear spin relaxation behaviour in large spin systems.

Molecular dynamics (MD) trajectories provide useful insights into molecular structure and dynamics. However, questions persist about the quantitative accuracy of those insights. Experimental NMR spin relaxation rates can be used as tests, but only if relaxation superoperators can be efficiently computed from MD trajectories - no mean feat for the quantum Liouville space formalism where matrix dimensions quadruple with each added spin 1/2. Here we report a module for the Spinach software framework that computes Bloch-Redfield-Wangsness relaxation superoperators (including non-secular terms and cross-correlations) from MD trajectories. Predicted initial slopes of nuclear Overhauser effects for sucrose trajectories using advanced water models and a force field optimised for glycans are within 25% of experimental values.

Skip that repeat DXA scan in these postmenopausal women.

Repeat bone density measurement offers no advantage in predicting fracture risk in postmenopausal women who do not have osteoporosis.

Motor cortical circuits contribute to crossed facilitation of trunk muscles induced by rhythmic arm movement.

Training of one limb improves performance of the contralateral, untrained limb, a phenomenon known as cross transfer. It has been used for rehabilitation interventions, i.e. mirror therapy, in people with neurologic disorders. However, it remains unknown whether training of the upper limb can induce the cross-transfer effect to the trunk muscles. Using transcranial magnetic stimulation over the primary motor cortex (M1) we examined motor evoked potentials (MEPs) in the contralateral erector spinae (ES) muscle before and after 30 min of unilateral arm cycling in healthy volunteers. ES MEPs were increased after the arm cycling. To understand the origin of this facilitatory effect, we examined short-interval intracrotical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in neural populations controlling in the ES muscle. Notably, SICI reduced after the arm cycling, while CMEPs remained the same. Using bilateral transcranial direct current stimulation (tDCS) in conjunction with 20 min of the arm cycling, the amplitude of ES MEPs increased to a similar extent as with 30 min of the arm cycling alone. These findings demonstrate that a single session of unilateral arm cycling induces short-term plasticity in corticospinal projections to the trunk muscle in healthy humans. The changes are likely driven by cortical mechanisms.

Vaccine Safety.

The details of vaccine development, licensing, and monitoring have never been more important and relevant to the health care conversation in the United States. The potential exists for a preventive medicine such as a vaccine to cause harm, and physicians and patients need to understand the real balance of risks and benefits of immunization. Vaccines given in the United States undergo rigorous testing before licensure as well as extensive postlicensure safety monitoring.

Impact of an automatic hospital probiotic protocol on Clostridioides (Clostridium) difficile infection (CDI) rates and CDI antibiotic usage in a community hospital setting.

The aim of the present study was to see how widespread preventative use of the probiotic Saccharomyces boulardii via automatic protocol in hospitalised patients receiving antibacterials affected rates of hospital-associated Clostridioides (Clostridium) difficile infection (HA-CDI). Rates of HA-CDI appeared to be similar between the pre-protocol and protocol periods. Use of CDI treatment antibiotics (oral metronidazole and oral vancomycin) was also similar. Laboratory-confirmed isolation of S. boulardii from sterile body sites was identified in five patients during the protocol versus only one case in the pre-protocol years.

NMR Resonance Assignment Methodology: Characterizing Large Sparsely Labeled Glycoproteins.

Characterization of proteins using NMR methods begins with assignment of resonances to specific residues. This is usually accomplished using sequential connectivities between nuclear pairs in proteins uniformly labeled with NMR active isotopes. This becomes impractical for larger proteins, and especially for proteins that are best expressed in mammalian cells, including glycoproteins. Here an alternate protocol for the assignment of NMR resonances of sparsely labeled proteins, namely, the ones labeled with a single amino acid type, or a limited subset of types, isotopically enriched with 15N or 13C, is described. The protocol is based on comparison of data collected using extensions of simple two-dimensional NMR experiments (correlated chemical shifts, nuclear Overhauser effects, residual dipolar couplings) to predictions from molecular dynamics trajectories that begin with known protein structures. Optimal pairing of predicted and experimental values is facilitated by a software package that employs a genetic algorithm, ASSIGN_SLP_MD. The approach is applied to the 36-kDa luminal domain of the sialyltransferase, rST6Gal1, in which all phenylalanines are labeled with 15N, and the results are validated by elimination of resonances via single-point mutations of selected phenylalanines to tyrosines. Assignment allows the use of previously published paramagnetic relaxation enhancements to evaluate placement of a substrate analog in the active site of this protein. The protocol will open the way to structural characterization of the many glycosylated and other proteins that are best expressed in mammalian cells.

UBC-Nepal Expedition: Cerebrovascular Responses to Exercise in Sherpa Children Residing at High Altitude.

Understanding the process of successful adaptation to high altitude provides valuable insight into the pathogenesis of conditions associated with impaired oxygen uptake and utilization. Prepubertal children residing at low altitude show a reduced cerebrovascular response to exercise in comparison to adults, and a transient uncoupling of cerebral blood flow to changes in the partial pressure of end-tidal CO2 (PETCO2); however, little is known about the cerebrovascular response to exercise in high-altitude native children. We sought to compare the cerebral hemodynamic response to acute exercise between prepubertal children residing at high and low altitude. Prepubertal children (n = 32; 17 female) of Sherpa descent (Sherpa children [SC]) at high altitude (3800 m, Nepal) and maturational-matched (n = 32; 20 female) children (lowland children [LLC]) residing at low altitude (342 m, Canada). Ventilation, peripheral oxygen saturation (SpO2), PETCO2, and blood velocity in the middle and posterior cerebral arteries (MCAv and PCAv) were continuously measured during a graded cycling exercise test to exhaustion. At baseline (BL), PETCO2 (-19 ± 4 mmHg, p < 0.001), SpO2 (-6.0% ± 2.1%, p < 0.001), MCAv (-12% ± 5%, p = 0.02), and PCAv (-12% ± 6%, p = 0.04) were lower in SC when compared with LLC. Despite this, the relative change in MCAv and PCAv during exercise was similar between the two groups (p = 0.99). Linear regression analysis demonstrated a positive relationship between changes in PETCO2 with MCAv in SC (R2 = 0.13, p > 0.001), but not in LLC (R2 = 0.03, p = 0.10). Our findings demonstrate a similar increase in intra-cranial perfusion during exercise in prepubertal SC, despite differential BL values and changes in PETCO2 and SpO2.

Perceptions of Parenting Residents Among Family Medicine Residency Directors.

BACKGROUND AND OBJECTIVES: Parenting during residency is increasingly common, and resident parents face unique demands on their time and emotional and cognitive resources. Physicians at all levels of training perceive negative impacts of parenting on career and family life. Surveys of program directors (PDs) in other specialties reveal concern about performance and quality of life of parenting residents. The primary aims of this study were to examine family medicine PDs' perceptions of parenting residents' performance and the adequacy of parenting support structures. METHODS: Data were collected from the 2017 Council of Academic Family Medicine (CAFM) Educational Research Alliance (CERA) Family Medicine Residency Program Directors survey. Directors provided the number and status of parenting residents and rated adequacy of parenting resources, resident performance, and impact of parenting on residents using a Likert scale. Results were compared between male/female PDs and male/female residents. RESULTS: Response rate was 57.1%. Less than half of PDs reported adequate parenting support structures in their program (46%). Over 40% of PDs reported that 81%-100% of female residents who take parental leave end up extending their residency training, the most common response category. PDs did not report gender-based differences in performance of parenting residents. PDs most often reported significantly worse well-being for female parenting residents but perceived improved well-being of male parents. CONCLUSIONS: Less than half of family medicine PDs feel their program has adequate parenting resources. Female parenting residents commonly extend residency training. PDs perceive parenting negatively impacts well-being of female residents, but not male residents.