ABSTRACT
Introduction: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. Aim: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Methods and Results: Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Conclusion: Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.
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In coastal waters, higher concentrations of microplastics (MPs) are generally related to densely populated and industrialized areas, but intense upwelling and offshore transport in the Eastern Boundary Upwelling Systems (EBUS) may influence this pattern. The Humboldt Current System (HCS) along the coast of northern-central Chile represents a perfect model to test whether the abundance of MP at the sea surface decreases with distance from land-based sources, e.g., river mouths, harbors, and submarine wastewater outfalls. The sea surface was sampled with a manta trawl to examine the abundance, composition, and distribution of floating MPs, and Generalized Additive Mixed Models (GAMMs) were performed to examine the relationship between MP abundance (particles km-2) and the distance to putative sources. MPs were found in all 57 net tows, with an average of â120,000 MP km-2 and maximum values of â1,500,000 MP km-2. The composition of MPs was dominated by fragments (>50% of the total count) and over 80% of all MPs were ≥1 mm. The combined effect of the various sources, spatially concentrated in urban areas, makes it difficult to distinguish their relative contributions, but the MP composition suggested that rivers are more important sources, followed by submarine wastewater outfalls and then harbors. A significant and steep negative relationship with the "distance to source" explained 15.2% of the variance of "MP abundance", suggesting rapid offshore displacement within the HCS. This is the first study to report this pattern along the edges of the South Pacific Subtropical Gyre (SPSG), revealing that continuous offshore transport of microplastic from land-based sources is occurring over large scales and contributing to the accumulation of microplastics in the center of the SPSG. However, the findings additionally suggested that processes at meso- and submeso-spatial scales (driven by geographic and seasonal variables) are disrupting the general pattern.
Subject(s)
Microplastics , Water Pollutants, Chemical , Plastics , Wastewater , Water Pollutants, Chemical/analysis , Environmental MonitoringABSTRACT
The fortieth anniversary of biocatalysis started at Ciba-Geigy and later at Novartis is a great time to pause and reflect on development of science and technology in this field. Enzyme-based synthesis became a highly valued enabling tool for pharmaceutical research and development over the last decades. In this perspective we aim to discuss how the scientific approaches and trends evolved over the time and present future challenges and opportunities.
Subject(s)
BiocatalysisABSTRACT
BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.
Subject(s)
Cardiomyopathy, Dilated , Precision Medicine , Female , Humans , Male , Middle Aged , Black People , Cardiomyopathy, Dilated/epidemiology , Cardiomyopathy, Dilated/ethnology , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/therapy , Defibrillators, Implantable , Drug Evaluation , Adult , Aged , White , Black or African American , United States/epidemiologyABSTRACT
Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
Subject(s)
American Indian or Alaska Native , Black People , Cardiomyopathy, Dilated , Hispanic or Latino , White People , Humans , American Indian or Alaska Native/genetics , Black People/genetics , Cardiomyopathy, Dilated/ethnology , Cardiomyopathy, Dilated/genetics , Cross-Sectional Studies , Genomics , Hispanic or Latino/genetics , White People/geneticsABSTRACT
INTRODUCTION: The 75th Ranger Regiment is an elite U.S. military special operations unit that conducted over 20 years of sustained combat operations. The Regiment has a history of providing novel and cutting-edge prehospital trauma care, advancing and translating medical initiatives, and documenting and reporting casualty care performance improvement efforts. MATERIALS AND METHODS: A retrospective case fatality rate (CFR) review, mortality review, and descriptive analysis of fatalities were conducted for battle-injured personnel assigned or attached to the 75th Ranger Regiment from 2001 to 2021 during combat operations primarily in Afghanistan and Iraq. Fatalities were evaluated for population characteristics, cause of death, mechanism of death, injury severity, injury survivability, and death preventability. RESULTS: A total of 813 battle injury casualties, including 62 fatalities, were incurred over 20 years and 1 month of continuous combat operations. The Regiment maintained a zero rate of prehospital preventable combat death. Additionally, no fatalities had a mechanism of death because of isolated extremity hemorrhage, tension pneumothorax, or airway obstruction. When comparing the CFR of the Regiment to the U.S. military population as a whole, the Regiment had a significantly greater reduction in the cumulative CFR as measured by the difference in average annual percentage change. CONCLUSIONS: Documentation and analysis of casualties and care, mortality and casualty reviews, and other performance improvement efforts can guide combatant commanders, medical directors, and fighting forces to reduce preventable combat deaths and the CFR. Early hemorrhage control, blood product resuscitation, and other lifesaving interventions should be established and maintained as a standard prehospital practice to mitigate fatalities with potentially survivable injuries.
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Penetrating injury to the head and neck accounts for a minority of trauma but significant morbidity in the US civilian population. The 3-zone anatomical framework has historically guided evaluation and management; however, the most current evidence-based protocols favor a no-zone, systems-based approach. In stable patients, a thorough physical examination and noninvasive imaging should be prioritized, with surgical exploration of the head and neck reserved for certain circumstances. Diagnostic and management decisions should be tailored to the mechanism of injury, history, physical examination, experience of personnel, availability of equipment, and clinical judgment.
Subject(s)
Neck Injuries , Wounds, Penetrating , Humans , Neck Injuries/diagnosis , Neck Injuries/surgery , Neck , Wounds, Penetrating/diagnosis , Wounds, Penetrating/surgery , Physical Examination , Clinical Protocols , Retrospective StudiesABSTRACT
BACKGROUND: Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS: Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS: A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS: Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.
Subject(s)
Cardiomyopathy, Dilated , Female , Humans , Male , Black People , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/genetics , Echocardiography , Ethnicity , Hispanic or Latino , Hypertrophy, Left Ventricular , Adult , Middle AgedABSTRACT
BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.
Subject(s)
Cardiomyopathy, Dilated , Humans , Cardiomyopathy, Dilated/diagnosis , Ethnicity , Family , Family Health , Risk AssessmentABSTRACT
The objective of this work is to examine the feasibility of revision endoscopic posterior costal cartilage graft (EPCCG) placement for posterior glottic stenosis (PGS) and bilateral vocal fold immobility (BVFI). Revision and primary cases were compared with respect to decannulation rates, and it was hypothesized that there would be no difference in outcomes. Twenty-one patients met inclusion criteria (14 primary, 7 revision). Thirteen (62%) had a primary indication of PGS, and 8 (42%) were for BVFI. There were no differences between revision and primary groups with respect to age, gender, or comorbidities (p > .05). There was no difference between groups with respect to decannulation rate (85% primary vs 100% revision, p = .32). Thus, revision EPCCG appears to have comparable results to primary EPCCG with respect to decannulation rate and time to decannulation. EPCCG may be a feasible alternative to open airway reconstruction for PGS and BVFI in selected patients.
Subject(s)
Costal Cartilage , Laryngostenosis , Larynx , Humans , Costal Cartilage/transplantation , Laryngostenosis/surgery , Endoscopy , Constriction, PathologicABSTRACT
As global awareness, science, and policy interventions for plastic escalate, institutions around the world are seeking preventative strategies. Central to this is the need for precise global time series of plastic pollution with which we can assess whether implemented policies are effective, but at present we lack these data. To address this need, we used previously published and new data on floating ocean plastics (n = 11,777 stations) to create a global time-series that estimates the average counts and mass of small plastics in the ocean surface layer from 1979 to 2019. Today's global abundance is estimated at approximately 82-358 trillion plastic particles weighing 1.1-4.9 million tonnes. We observed no clear detectable trend until 1990, a fluctuating but stagnant trend from then until 2005, and a rapid increase until the present. This observed acceleration of plastic densities in the world's oceans, also reported for beaches around the globe, demands urgent international policy interventions.
Subject(s)
Smog , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Plastics , Environmental Monitoring , Oceans and Seas , Waste Products/analysisABSTRACT
Heavy metals, including mercury (Hg) and cadmium (Cd), occur naturally or anthropogenically and are considered toxic to the environment and human health. However, studies on heavy metal contamination focus on locations close to industrialized settlements, while isolated environments with little human activity are often ignored due to perceived low risk. This study reports heavy metal exposure in Juan Fernandez fur seals (JFFS), a marine mammal endemic to an isolated and relatively pristine archipelago off the coast of Chile. We found exceptionally high concentrations of Cd and Hg in JFFS faeces. Indeed, they are among the highest reported for any mammalian species. Following analysis of their prey, we concluded that diet is the most likely source of Cd contamination in JFFS. Furthermore, Cd appears to be absorbed and incorporated into JFFS bones. However, it was not associated with mineral changes observed in other species, suggesting Cd tolerance/adaptations in JFFS bones. The high levels of silicon found in JFFS bones may counteract the effects of Cd. These findings are relevant to biomedical research, food security and the treatment of heavy metal contamination. It also contributes to understanding the ecological role of JFFS and highlights the need for surveillance of apparently pristine environments.
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The capture of a soft spherical particle in a rectangular slit leads to a nonmonotonic pressure-flow rate relation at low Reynolds number. Simulations reveal that the flow induced deformations of the trapped particle focus the streamlines and pressure drop to a small region. This increases the resistance to flow by several orders of magnitude as the driving pressure is increased. As a result, two regimes are observed in experiments and simulations: a flow-dominated regime for small particle deformations, where flow rate increases with pressure, and an elastic-dominated regime in which solid deformations block the flow.
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Primary osteosarcomas are rarely seen in areas other than bone, although they can occur in sites such as the thigh, anal region, hand, etc. We present a case of primary extraskeletal osteosarcoma of the thyroid, of which there are only 29 previous reported cases. Presentations and treatment options for this type of tumor vary. Through this case report, we discuss the similarities and differences of the patient's presentation compared with other documented cases, imaging, the rationale behind treatment, and the current clinical course.
Subject(s)
Bone Neoplasms , Osteosarcoma , Soft Tissue Neoplasms , Humans , Thyroid Gland , Osteosarcoma/diagnostic imaging , Osteosarcoma/surgeryABSTRACT
Microscopy is often the first step in microplastic analysis and is generally followed by spectroscopy to confirm material type. The value of microscopy lies in its ability to provide count, size, color, and morphological information to inform toxicity and source apportionment. To assess the accuracy and precision of microscopy, we conducted a method evaluation study. Twenty-two laboratories from six countries were provided three blind spiked clean water samples and asked to follow a standard operating procedure. The samples contained a known number of microplastics with different morphologies (fiber, fragment, sphere), colors (clear, white, green, blue, red, and orange), polymer types (PE, PS, PVC, and PET), and sizes (ranging from roughly 3-2000 µm), and natural materials (natural hair, fibers, and shells; 100-7000 µm) that could be mistaken for microplastics (i.e., false positives). Particle recovery was poor for the smallest size fraction (3-20 µm). Average recovery (±StDev) for all reported particles >50 µm was 94.5 ± 56.3%. After quality checks, recovery for >50 µm spiked particles was 51.3 ± 21.7%. Recovery varied based on morphology and color, with poorest recovery for fibers and the largest deviations for clear and white particles. Experience mattered; less experienced laboratories tended to report higher concentration and had a higher variance among replicates. Participants identified opportunity for increased accuracy and precision through training, improved color and morphology keys, and method alterations relevant to size fractionation. The resulting data informs future work, constraining and highlighting the value of microscopy for microplastics.
Subject(s)
Microplastics , Water Pollutants, Chemical , Environmental Monitoring , Humans , Microscopy , Plastics/analysis , Polymers , Polyvinyl Chloride/analysis , Water/analysis , Water Pollutants, Chemical/analysisABSTRACT
Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.
Subject(s)
Cardiomyopathy, Dilated/epidemiology , Family Health/statistics & numerical data , Racial Groups/statistics & numerical data , Adult , Age Factors , Black People/statistics & numerical data , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/ethnology , Confidence Intervals , Cross-Sectional Studies , Early Diagnosis , Family Health/ethnology , Female , Hispanic or Latino/statistics & numerical data , Humans , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/ethnology , Male , Middle Aged , Prevalence , Racial Groups/ethnology , Risk , United States/epidemiology , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/epidemiology , Ventricular Dysfunction, Left/ethnology , White People/statistics & numerical dataABSTRACT
OBJECTIVE: Exertional heat stroke (EHS), characterised by a high core body temperature (Tcr) and central nervous system (CNS) dysfunction, is a concern for athletes, workers and military personnel who must train and perform in hot environments. The objective of this study was to determine whether algorithms that estimate Tcr from heart rate and gait instability from a trunk-worn sensor system can forward predict EHS onset. METHODS: Heart rate and three-axis accelerometry data were collected from chest-worn sensors from 1806 US military personnel participating in timed 4/5-mile runs, and loaded marches of 7 and 12 miles; in total, 3422 high EHS-risk training datasets were available for analysis. Six soldiers were diagnosed with heat stroke and all had rectal temperatures of >41°C when first measured and were exhibiting CNS dysfunction. Estimated core temperature (ECTemp) was computed from sequential measures of heart rate. Gait instability was computed from three-axis accelerometry using features of pattern dispersion and autocorrelation. RESULTS: The six soldiers who experienced heat stroke were among the hottest compared with the other soldiers in the respective training events with ECTemps ranging from 39.2°C to 40.8°C. Combining ECTemp and gait instability measures successfully identified all six EHS casualties at least 3.5 min in advance of collapse while falsely identifying 6.1% (209 total false positives) examples where exertional heat illness symptoms were neither observed nor reported. No false-negative cases were noted. CONCLUSION: The combination of two algorithms that estimate Tcr and ataxic gate appears promising for real-time alerting of impending EHS.
Subject(s)
Heat Stress Disorders , Heat Stroke , Gait , Heat Stress Disorders/diagnosis , Heat Stroke/diagnosis , Hot Temperature , Humans , TemperatureABSTRACT
Our understanding of the novel coronavirus, COVID-19, is growing; yet, there remains much we do not understand, and unique presentations are abundant. One potential presentation is retropharyngeal edema, defined as fluid in the retropharyngeal space. Multiplanar imaging with computed tomography or magnetic resonance imaging is ideal for characterizing and diagnosing these fluid collections rapidly as possible life-threatening complications may develop (eg, airway obstruction and mediastinitis). Here, we discuss the presentation, imaging identification, treatment, and recovery of retropharyngeal fluid collection in 2 COVID-19 cases. The significance of this article is to suggest conservative management as a viable treatment option for retropharyngeal fluid collection, as opposed to incision and drainage, in the setting of COVID-19.
Subject(s)
COVID-19 , Mediastinitis , Retropharyngeal Abscess , COVID-19/complications , Drainage/methods , Humans , Mediastinitis/therapy , Retropharyngeal Abscess/diagnostic imaging , Retropharyngeal Abscess/therapy , Tomography, X-Ray Computed/methodsABSTRACT
A patient with severe mitral regurgitation and chronic systolic heart failure taking inotropic support at home presents for transcatheter edge-to-edge mitral valve repair, complicated by torrential mitral regurgitation from damaged mitral leaflets requiring escalating mechanical circulatory support and ultimately expedited orthotopic heart transplantation. (Level of Difficulty: Intermediate.).
ABSTRACT
Upper-limb prostheses are subject to high rates of abandonment. Prosthesis abandonment is related to a reduced sense of embodiment, the sense of self-location, agency, and ownership that humans feel in relation to their bodies and body parts. If a prosthesis does not evoke a sense of embodiment, users are less likely to view them as useful and integrated with their bodies. Currently, visual feedback is the only option for most prosthesis users to account for their augmented activities. However, for activities of daily living, such as grasping actions, haptic feedback is critically important and may improve sense of embodiment. Therefore, we are investigating how converting natural haptic feedback from the prosthetic fingertips into vibrotactile feedback administered to another location on the body may allow participants to experience haptic feedback and if and how this experience affects embodiment. While we found no differences between our experimental manipulations of feedback type, we found evidence that embodiment was not negatively impacted when switching from natural feedback to proximal vibrotactile feedback. Proximal vibrotactile feedback should be further studied and considered when designing prostheses.