Connecting Molecular Exchange Dynamics to Stress Relaxation in Phase-Separated Dynamic Covalent Networks.

A suite of phase separated dynamic covalent networks based on highly tunable dynamic benzalcyanoacetate (BCA) thia-Michael acceptors are investigated. In situ kinetic studies on small molecule model systems are used in conjunction with macroscopic characterization of phase stability and stress relaxation to understand how the molecular dynamics relate to relaxation modes. Electronic modification of the BCA unit strongly impacts the exchange dynamics (particularly the rate of dissociation) and the overall equilibrium constant (Keq) of the system, with electron-withdrawing groups leading to decreased dissociation rate and increased Keq. Critically, below a chemistry-defined temperature cutoff (related to the stability of the hard phase domains), the stress relaxation behavior of these phase separated materials is dominated by the molecular exchange dynamics, allowing for networks with a tailored thermomechanical response.

A geopositioned and evidence-graded pan-species compendium of Mayaro virus occurrence.

Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compendium, which includes both point and polygon locations linked to occurrence data documented from its discovery in 1954 until 2022. We describe all methods used to develop the database including data collection, georeferencing, management and quality-control. We also describe a customized grading system used to assess the quality of each study included in our review. The result is a comprehensive, evidence-graded database of confirmed MAYV occurrence in humans, non-human animals, and arthropods to-date, containing 262 geo-positioned occurrences in total. This database - which can be updated over time - may be useful for local spill-over risk assessment, epidemiological modelling to understand key transmission dynamics and drivers of MAYV spread, as well as identification of major surveillance gaps.

Biologics in Spine Fusion.

Achieving fusion in spine surgery can be challenging because of patient factors such as smoking and diabetes. The consequences of pseudarthrosis can be severe, including pain, instability, and additional surgery. Autologous iliac crest bone graft is the historical standard for augmenting spine fusion, providing high rates of fusion throughout the cervical, thoracic, and lumbar spine. Harvest of autologous iliac crest bone can be associated with comorbidities and this has led to development of alternative biologic materials to enhance spine fusion. Substitutes include various forms of allograft products including decellularized allograft; demineralized bone matrix; synthetic materials including bioactive glass; and autologous and allograft mesenchymal stem cells. Bone morphogenetic proteins can be efficacious for fusion but have significant risks and are not suitable for all spine procedures. There is a wide variety of utilization of biologics for spine fusion that are influenced by spinal region, surgeon preference, surgical training, health system formulary, and cost.

Online Virtual Patient Cases vs. Weekly Classroom Lectures in an Internal Medicine Clerkship: Effects on Military Learner Outcomes.

INTRODUCTION: Virtual patient cases (VPCs), a type of simulated, interactive electronic learning, are a potentially important tool for military health care providers in austere or pandemic settings to maintain skills but need more validation. Our military internal medicine clerkship is spread across military treatment facilities around the country and has 15 weekly live student lectures, but students randomly miss the first, second, or third 5 weeks due to their psychiatry clerkship. We hypothesized that VPCs would be an adequate replacement for lost lectures. MATERIALS AND METHODS: We compared live lectures to a web-based VPC and analyzed the academic outcomes of 734 students from 2015 to 2022. RESULTS: Using our end-of-clerkship Script Concordance Test (SCT) as the primary outcome, there was no significant difference in performance between the 2 learning methods (VPC, 63.9% correct; lectures 63.2%, P = .27). After controlling for gender, baseline knowledge, and the total number of VPCs completed, there was still not a statistically significant difference between teaching methods (F(1,728) = 0.52, P = .47). There was also no significant differences in all other clerkship outcomes including National Board of Medical Examiner and Objective Structured Clinical Examination scores. CONCLUSION: VPCs appear noninferior at teaching clinical reasoning as measured by SCT. VPCs might be substituted for traditional, live lectures in clerkships when time or other resources are limited, in austere environments such as military deployments, or during conditions limiting interpersonal contact such as pandemics but are not a complete substitution for in-person learning.

A descriptive analysis of dengue in Peace Corps Volunteers, 2000-2019.

BACKGROUND: Peace Corps Volunteers (PCVs) are a unique expatriate population at risk for dengue. Previous studies examined travelers or lacked demographic information about expatriates. We examined dengue incidence among PCVs before and after deployment of an electronic medical record (EMR) to assess temporal and demographic factors. METHODS: Dengue cases within Peace Corps' Epidemiologic Surveillance System from 2000 to 2019 were identified using a standard case definition, and two timeframes were compared: pre-EMR 2000-2015 and post-EMR 2016-2019. RESULTS: Annual infections occurred in a roughly 3-year cyclic pattern from 2007 to 2019. Incidence rate decreased from 1.35 cases per 100 dengue Volunteer-years (95% CI 1.28-1.41) in 2000-2015 to 1.25 cases (95% CI 1.10-1.41) in 2016-2019. Among PCVs who served from 2016 to 2019, the majority of infections occurred in females and 20-29 year olds, and 7% were medically evacuated. Among PCVs who served from 2015 to 2019, 21% were hospitalized in-country. CONCLUSIONS: Among PCVs, a non-significant decrease in dengue incidence occurred from 2000-2015 to 2016-2019. Annual infection rates peaked every three years, offering opportunities for targeted prevention efforts. Dengue infection in PCVs appears to mimic the overall demographic of Peace Corps. Expatriates like PCVs are at an increased risk for dengue infection compared to short-term travelers.

Dengue Virus Infections among Peace Corps Volunteers in Timor-Leste, 2018-2019.

Dengue is an ongoing health risk for Peace Corps Volunteers (PCVs) working in the tropics. On May 2019, the Peace Corps Office of Health Services notified the Centers for Disease Control and Prevention (CDC) of a dengue outbreak among PCVs in Timor-Leste. The purpose of this investigation was to identify the clinical, demographic, and epidemiological characteristics of PCVs with dengue and recommend dengue preventive measures. To identify PCVs with dengue and describe disease severity, the medical records of PCVs reporting fever during September 2018-June 2019 were reviewed. To identify factors associated with dengue virus (DENV) infection, we administered a questionnaire on demographics, travel history, and mosquito avoidance behaviors and collected blood specimens to detect the anti-DENV IgM antibody to diagnose recent infection. Of 35 PCVs in-country, 11 (31%) tested positive for dengue (NS1, IgM, PCR), eight requiring hospitalization and medical evacuation. Among 27 (77%) PCVs who participated in the investigation, all reported having been recently bitten by mosquitoes and 56% reported being bitten most often at home; only 16 (59%) reported having screens on bedroom windows. Nearly all (93%) PCVs reported using a bed net every night; fewer (70%) reported using mosquito repellent at least once a day. No behaviors were significantly associated with DENV infection. Raising awareness of dengue risk among PCVs and continuing to encourage mosquito avoidance behavior to prevent dengue is critical. Access to and use of measures to avoid mosquito bites should be improved or implemented. Peace Corps medical officers should continue to receive an annual refresher training on dengue clinical management.

Tibial Intramedullary Nail From a Suprapatellar Approach in a Semi-Extended Position.

An intramedullary nail is a common and reliable treatment option for diaphyseal tibial fractures. One such approach for this technique is suprapatellar. This video shows the surgical technique of a tibial nail through a suprapatellar approach in a semi-extended position in a 22-year-old man with a distal third tibial shaft fracture.

The Production of Antibiotic Cement Beads.

The use of antibiotic beads in open fracture cases can lead to decreased rates of infection and surgeon production is associated with significant time and cost savings. This video demonstrates production of antibiotic impregnated polymethylmethacrylate beads used in the setting of a grade IIIB open tibial shaft fracture.

Radial Head Replacement Through a Kocher Approach.

PURPOSE: Radial head fractures are some of the most common elbow fractures. Fractures with 3 or more fracture fragments have been shown to have worse outcomes when treated with open reduction and internal fixation (ORIF). Radial head replacement offers an alternative treatment for those more comminuted radial head fractures. METHODS: Three-part radial head fractures make anatomical reduction more difficult to obtain with ORIF. Radial head fractures requiring replacement have shown good clinical outcomes. As a result, radial head arthroplasty offers a good treatment option for 3-or-more-part radial head fractures. RESULTS: This video presents a case of a radial head arthroplasty for a 3-part radial head fracture in a 23-year-old man. The radial head implant provides a smooth and concentric surface for articulation with the capitellum while providing stability to the elbow. CONCLUSIONS: Radial head replacement provides a good alternative to ORIF, producing similar elbow range of motion and providing good stability compared with the contralateral elbow.

Posterior Approach for a Cemented Hemiarthroplasty.

PURPOSE: Femoral neck fractures are common injuries with over 1 million occurring yearly. This video demonstrates a case of a displaced femoral neck fracture treated with a cemented hemiarthroplasty through a posterior approach. METHODS: Multiple approaches to the hip for arthroplasty have been described, each with advantages and disadvantages. Careful technique is critical to success. RESULTS: This presents a case of a displaced femoral neck fracture treated with a cemented hemiarthroplasty through a posterior approach. CONCLUSIONS: Displaced femoral neck fractures are common fractures. The posterior approach for cemented hemiarthroplasty is a safe, reproducible technique.

Patient Preferences in Office-Based Orthopedic Care: A Prospective Evaluation.

Patient satisfaction has become a topic of interest within orthopedics as the landscape of provider reimbursement continues to evolve to reward value of care. Online internet physician rating sites are becoming increasingly popular ways for patients to subjectively express their provider experience. Understanding what patients value during their episode of care is important in the modern healthcare environment. The purpose of this study is to determine what preferences, if any, patients have when selecting their physician and how they experience care in an outpatient orthopedic setting. A prospective survey was electronically administered to 212 patients in an adult reconstruction clinic. One hundred ninety-six patients (92.5%) completed the survey. Demographic questions regarding age, sex, ethnicity, and prior adult reconstruction surgical history were obtained. When patients were asked how much time they would like the doctor to spend with them on a routine visit, the most common answer was 10 to 15 minutes (41.3%), with only 10.2% patients desiring >20 minutes. The majority of patients (83.1%) believe ≥30 minutes is too long to wait to see their surgeon. Less than half of patients (41.8%) stated that they would feel as though they were receiving below average care if seen only by a nurse practitioner or physician's assistant at a postoperative visit. Patients reported no significant age, gender, or ethnicity preferences for their physician. Recommendations from friends or other physicians was the most common (66.4%) way for patients to find their physicians, while 12.2% utilized online rating sites during their search. Optimizing patient experiences in the office may include keeping wait times to <30 minutes and educating patients on the roles of physician extenders. More work needs to be done to further elucidate variables influencing the subjective patient experience with their orthopedic care.

Injections for Knee Osteoarthritis: Corticosteroids, Viscosupplementation, Platelet-Rich Plasma, and Autologous Stem Cells.

This article reviews the benefits of corticosteroid, viscosupplementation, platelet-rich plasma, and autologous mesenchymal stem cell injections for the treatment of patients with knee osteoarthritis. Integrating injections into both clinical and surgical practices is complicated given existing health insurance reimbursement policies. This review describes the outcomes associated with these interventions and appropriate methods of navigating the existing reimbursement pathways to help providers implement these treatments into their practices.

Extended-spectrum ß-lactamase-producing Enterobacteriaceae in cell phones of health care workers from Peruvian pediatric and neonatal intensive care units.

BACKGROUND: Health care workers (HCWs) use their mobile phones during working hours or medical care. There is evidence that the instruments are colonized with pathogenic microorganisms. Here, we describe levels of Enterobacteriaceae contamination (EC) in cell phones and the risk factors associated with EC in Peruvian intensive care units (ICUs). METHODS: This was a 5-month cohort study among 114 HCWs of 3 pediatric and 2 neonatology ICUs from 3 Peruvian hospitals. A baseline survey collected data on risk factors associated with EC. Swabs were collected from HCWs' phones every other week. RESULTS: Three-quarters of HCWs never decontaminated their phones, and 47% reported using the phones in the ICU >5 times while working. EC was frequent across samplings and sites and was substantially higher in subjects with longer follow-up. Potential risk factors identified did not have strong associations with positive samples (relative risk, 0.7-1.5), regardless of significance. Half of the phones were colonized with an Enterobacteriaceae at least once during the 4 samplings attained on average during the study period. Half of the isolates were multidrug resistant (MDR), and 33% were extended-spectrum ß-lactamase producers. CONCLUSIONS: EC on HCWs' phones was frequent and apparently randomly distributed through the hospitals without clear clustering or strongly associated risk factors for having a positive sample. Based on the level of EC, phones may be considered as potential bacterial reservoirs of MDR and ESBL bacteria.

Safety of antimalarial medications for use while scuba diving in malaria Endemic Regions.

BACKGROUND: Recreational diving occurs annually in areas of the world where malaria is endemic. The safety and efficacy of antimalarials for travelers in a hyperbaric environment is unknown. Of particular concern would be medications with adverse effects that could either mimic diving related illnesses such as barotrauma, decompression sickness (DCS) and gas toxicities, or increase the risk for such illnesses. METHODS: We conducted a review of PubMed and Cochrane databases to determine rates of neurologic adverse effects or other effects from antimalarials that may be a problem in the diving environment. RESULTS: One case report was found on diving and mefloquine. Multiple case reports and clinical trials were found describing neurologic adverse effects of the major chemoprophylactic medications atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine. CONCLUSIONS: Of the available literature, atovaquone/proguanil and doxycycline are most likely the safest agents and should be preferred; atovaquone/proguanil is superior due to reduced rates of sunburn in the marine environment. Primaquine also appears to be safe, but has reduced efficacy against P. falciparum; mefloquine possesses the highest rate of neurologic side effects and therefore these agents should be limited to extreme cases of patients intolerant to other agents. Chloroquine appears unsafe in the hyperbaric environment and should be avoided. More studies are required to include database reviews of returned divers traveling to malaria endemic areas and randomized controlled trials in the hyperbaric environments.

Japanese encephalitis: a review of clinical guidelines and vaccine availability in Asia.

Travelers to Asia are at risk for acquiring Japanese Encephalitis (JEV), an arbovirus with high rates of morbidity and mortality. Recent advances in vaccination resulting in vaccines with low rates of side effects have strengthened the rationale to vaccinate more travelers to this region, as reflected in many updated national guidelines for prevention of disease in travelers. Vaccines however still require a complex pre-travel schedule and are costly, often leading to a requirement or desire for a vaccination option in the destination country. We explore current national guidelines for prevention of Japanese Encephalitis and seek to provide information on availability of JEV vaccines in various Asian countries.

Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts.

Diabetes is an independent risk factor for cardiovascular disease that can eventually cause cardiomyopathy and heart failure. Cardiac fibroblasts (CF) are the critical mediators of physiological and pathological cardiac remodeling; however, the effects of hyperglycemia on cardiac fibroblast function and differentiation is not well known. Here, we performed a comprehensive investigation on the effects of hyperglycemia on cardiac fibroblasts and show that hyperglycemia enhances cardiac fibroblast function and differentiation. We found that high glucose treatment increased collagen I, III, and VI gene expression in rat adult cardiac fibroblasts. Interestingly, hyperglycemia increased CF migration and proliferation that is augmented by collagen I and III. Surprisingly, we found that short term hyperglycemia transiently inhibited ERK1/2 activation but increased AKT phosphorylation. Finally, high glucose treatment increased spontaneous differentiation of cardiac fibroblasts to myofibroblasts with increasing passage compared with low glucose. Taken together, these findings suggest that hyperglycemia induces cardiac fibrosis by modulating collagen expression, migration, proliferation, and differentiation of cardiac fibroblasts.

The autonomic effects of cardiopulmonary decompression sickness in swine using principal dynamic mode analysis.

Methods to predict onset of cardiopulmonary (CP) decompression sickness (DCS) would be of great benefit to clinicians caring for stricken divers. Principal dynamic mode (PDM) analysis of the electrocardiogram has been shown to provide accurate separation of the sympathetic and parasympathetic tone dynamics. Nine swine (Sus scrofa) underwent a 15-h saturation dive at 184 kPa (60 ft. of saltwater) in a hyperbaric chamber followed by dropout decompression, whereas six swine, used as a control, underwent a 15-h saturation dive at 15 kPa (5 ft. of saltwater). Noninvasive electrocardiograms were recorded throughout the experiment and autonomic nervous system dynamics were evaluated by heart rate series analysis using power spectral density (PSD) and PDM methods. We observed a significant increase in the sympathetic and parasympathetic tones using the PDM method on average 20 min before DCS onset following a sudden induction of decompression. Parasympathetic activities remained elevated, but the sympathetic modulation was significantly reduced at onset of cutis and CP DCS signs, as reported by a trained observer. Similar nonsignificant observations occurred during PSD analysis. PDM observations contrast with previous work showing that neurological DCS resulted in a >50% reduction in both sympathetic and parasympathetic tone. Therefore, tracking dynamics of the parasympathetic tones via the PDM method may allow discrimination between CP DCS and neurological DCS, and this significant increase in parasympathetic tone has potential use as a marker for early diagnosis of CP DCS.

Interrupted oxygen pre-breathing and decompression outcomes in swine.

BACKGROUND: Rescue from a disabled submarine may result in substantial risk for severe decompression sickness (DCS) among survivors. Oxygen prebreathe (OPB) before rapid decompression has been shown to significantly reduce risk or delay onset for severe DCS in animals. However, the duration of this benefit remains unknown and might even be lost if a delay between the prebreathe period to initiation of recompression therapy allows for nitrogen reaccumulation. METHODS: We hypothesized that the benefit of OPB would be lost following subsequent periods of air interruption in a 70-kg swine saturation model. Following OPB of 45 or 60 min with varying periods (30, 45, 60 min) of air interruption, 61 swine exposed to 2.7 ATA for 22 h were rapidly decompressed. Swine without OPB served as negative controls and swine treated with 45 min of OPB without air interruption served as positive controls. RESULTS: Comparing experimental groups for Type II DCS incidence showed OPB120/60 being the only experimental group (11%) statistically different than the negative control group OPB0 (80%). Log rank tests comparing Type II DCS free survival only showed statistically significant differences for OPB45/60 compared to positive control group OPB45, while, more importantly, demonstrating a significant difference for OPB120/60 compared to that approximated for OPB45, indicating a significant reversal of the air interruption effects with longer OPB on Type II DCS disease free survival. DISCUSSION: Based on these findings we concluded that the protective effects of OPB against severe DCS are reduced with increasing periods of air interruption.

Repurposing screens identify rifamycins as potential broad-spectrum therapy for multidrug-resistant Acinetobacter baumannii and select agent microorganisms.

AIMS: Estimates suggest that the drug discovery and development processes take between 10 and 15 years, with costs ranging between US$500 million and $2 billion. A growing number of bacteria have become resistant to approved antimicrobials. For example, the Gram-negative bacterium Acinetobacter baumannii has become multidrug resistant (MDR) and is now an important pathogen to the US military in terms of wound infections. Industry experts have called for a 'disruptive' transformation of the drug discovery process to find new chemical entities for treating drug-resistant infections. One such attempt is drug 'repurposing' or 'repositioning' - that is, identification and development of new uses for existing or abandoned pharmacotherapies. MATERIALS & METHODS: Using a novel combination of screening technologies based on cell growth and cellular respiration, we screened 450 US FDA-approved drugs from the NIH National Clinical Collection against a dozen clinical MDR A. baumannii (MDRAb) isolates from US soldiers and Marines. We also screened the collection against a diverse set of select agent surrogate pathogens. RESULTS: Seventeen drugs showed promising antimicrobial activity against all MDRAb isolates and select agent surrogates; three of these compounds - all rifamycins - were found to be effective at preventing growth and preventing cellular respiration of MDRAb and select agent surrogate bacteria when evaluated in growth prevention assays, highlighting the potential for repurposing. CONCLUSION: We report the discovery of a class of known compounds whose repurposing may be useful in solving the current problem with MDRAb and may lead to the discovery of broad-spectrum antimicrobials.

Executive summary: Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: endorsed by the Infectious Diseases Society of America and the Surgical Infection Society.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.