Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.

The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses.

Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes.

Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. Current strategies for developing pan-coronavirus countermeasures have largely focused on the receptor binding domain () and S2 regions of the coronavirus Spike protein; it has been unclear whether the N-terminal domain () is a viable target for universal vaccines and broadly neutralizing antibodies (). Additionally, many RBD-targeting Abs have proven susceptible to viral escape.

Functional antibodies exhibit light chain coherence.

The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. Each chain contains three complementarity-determining regions (CDR1-CDR3), which contribute to antigen specificity.

Divergent and Regioselective Synthesis of Pyrazolo[1,5-]pyridines and Imidazo[1,5-]pyridines.

Nitrogenous heterocycles are ubiquitous in pharmaceuticals and drug-like compounds; however, regioselective synthesis has proved challenging. Herein we report our efforts to develop a regioselective method for the synthesis of pyrazolo[1,5-]pyridines and the serendipitous discovery of a protocol for the regioselective formation of imidazo[1,5-]pyridines. Together, these transformations allow for the rapid and selective formation of two important heterocyclic motifs from a common intermediate.

Confusion recurs 2 weeks after fall.

A 77-year-old woman presented to the emergency department complaining of a headache following a syncopal episode (while standing) earlier that day. She said that she'd lost consciousness for several minutes, and then experienced several minutes of mild confusion that resolved spontaneously. On physical exam, she was oriented to person and place, but not time.

Automation and apps for clinical dental biomechanics.

Objectives: The aim of this research summary is to introduce the current and ongoing work using smartphone video, tracking markers to measure musculoskeletal disorders of cranial and mandibular origin, and the potential significance of the technology to doctors and therapists.

Method: The MPA™ biomechanical measuring apps are in beta trials with various doctors and therapists. The technique requires substantial image processing and statistical analysis, best suited to server-side processing.

Bedside rounds versus board rounds in an emergency department.

Background: Our objective was to gain insight into whether bedside rounding at shift turnover in the emergency department improved education quality, as compared with board rounds. Board rounds are commonly used in the emergency department, where the teams review the patient and transfer care near a computer screen or written board, rather than at the patient's bedside. The impact on teaching or patient care has not been extensively compared between the two approaches.

Exercise collapse associated with sickle cell trait (ECAST): case report and literature review.

Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors.

Computational and ¹³C investigations of the diazadienes and oxazadienes formed via the rearrangement of methylenecyclopropyl hydrazones and oximes.

Computational and further experimental investigations of the previously reported diazadienes, obtained via the rearrangement of methylenecyclopropyl hydrazone 1 are reported. Calculations at the CCSD(T)/cc-pVTZ//B3LYP/6-31G(d) level of theory indicate that the initially reported product 3 would, if formed, undergo rapid electrocyclic ring opening and, hence, would be unstable under the reaction conditions. Based on this computational prediction, further analysis of the (13)C NMR spectrum, previously attributed to 3, led to the revision of structure 3 to that of its N-tosylaminopyrrole constitutional isomer 11.

Evaluation of Contingency Telemedical Support to Improve Casualty Care at a Simulated Military Intermediate Resuscitation Facility: The EM-ANGEL Study.

Objective: We sought to determine whether Contingency Telemedical Support (CTS) improves the success rate and efficiency of primary care providers performing critical actions during simulated combat trauma resuscitation. Critical actions included advanced airway, chest decompression, extremity hemorrhage control, hypothermia prevention, antibiotics and analgesics, and hypotensive resuscitation, among others.

Background: Recent studies report improved survival associated with skilled triage and treatment in the out-of-hospital/preoperative phase of combat casualty care.

Propofol for benzodiazepine-refractory alcohol withdrawal in a non-mechanically ventilated patient.

Long-term alcohol use confers neurochemical changes in response to alcohol's exogenous inhibitory effects. Downregulation and decreased sensitivity of γ-aminobutyric acid receptors render benzodiazepines less effective at controlling psychomotor agitation. Propofol has been reported to have successfully relieved alcohol withdrawal syndrome (AWS) symptoms in part because of activation of γ-aminobutyric acid channels in combination with antagonism of excitatory amino acids such as N-methyl-D-aspartate.

Case reports: Death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA).

Dietary supplements and their associated adverse events are not uncommon in the U.S. military, and selected dietary supplements have been associated with a number of nontraumatic deaths in service members.

Adenosine signaling promotes regeneration of pancreatic β cells in vivo.

Diabetes can be controlled with insulin injections, but a curative approach that restores the number of insulin-producing β cells is still needed. Using a zebrafish model of diabetes, we screened ~7,000 small molecules to identify enhancers of β cell regeneration. The compounds we identified converge on the adenosine signaling pathway and include exogenous agonists and compounds that inhibit degradation of endogenously produced adenosine.

Advanced airway management in combat casualties by medics at the point of injury: a sub-group analysis of the reach study.

Unlabelled: background: Optimal airway management protocols for the prehospital battlefield setting have not been defined. Airway management strategies in this environment must take into account the injury patterns, the environment and training requirements of military prehospital providers.

Methods: This is a post-hoc, sub-group analysis of the Registry of Emergency Airways Arriving at Combat Hospitals or REACH database.

Dachshund homologues play a conserved role in islet cell development.

All metazoans use insulin to control energy metabolism, but they secrete it from different cells: neurons in the central nervous system in invertebrates and endocrine cells in the gut or pancreas in vertebrates. Despite their origins in different germ layers, all of these insulin-producing cells share common functional features and gene expression patterns. In this study, we tested the role in insulin-producing cells of the vertebrate homologues of Dachshund, a transcriptional regulator that marks the earliest committed progenitors of the neural insulin-producing cells in Drosophila.

Myeloproliferative disorders and the hyperviscosity syndrome.

Myeloproliferative disorders and the serum hyperviscosity syndrome can rapidly manifest with emergent presentations. Hyperviscosity occurs from pathologic elevations of either the cellular or acellular (protein) fractions of the circulating blood. Classic hyperviscosity syndrome presents with the triad of bleeding diathesis, visual disturbances, and focal neurologic signs.

Traumatic brain injury complicated by environmental hyperthermia.

Temperature variations after traumatic brain injury are common and devastating. This has been shown most clearly with hypothermia, but the complications associated with hyperthermia in the setting of traumatic brain injury can be just as problematic. We present the case of a soldier with traumatic brain injury exposed to environmental temperatures of 115-120 degrees F with a core temperature of over 108 degrees F.