Cerebral fat embolism syndrome mimicking thrombotic thrombocytopenic purpura in a patient with Hemoglobin SC disease

Case Presentation A 54 year‐old man with hemoglobin SC disease (HbSC) and a history of substance abuse presented to the Emergency Department from a nursing home with two days of progressive weakness, shortness of breath, and lower back pain. He developed a fever, hypoxia, and tachycardia on the day of admission. He did not have any recent changes in medications, and his family as well as the nursing home staff denied any access to illicit drugs

Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

Myelopathy is an increasingly recognized presentation of many antibody-mediated neuroinflammatory disorders. While specific features of certain autoimmune myelopathies such as aquaporin-4 antibody associated neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are well-characterized, other less commonly seen antibody-associated myelopathies are not as well-defined. These include but are not limited to, Hu/ANNA1, anti-glial fibrillary acidic protein (GFAP), anti-CV2/collapsin response mediator protein (CRMP5), and amphiphysin. Here, we review the mentioned more common antibody mediated myelopathies as well those that as less common, followed by a review of differentials that may mimic these disorders

The differential impact of interactions outside the organization on employee well-being

Ministry of Education, Singapore under its Academic Research Funding Tier

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Socioeconomic mobility and talent utilization of workers from poorer backgrounds: The overlooked importance of within-organization dynamics

Socioeconomic mobility, or the ability of individuals to improve their socioeconomic standing through merit-based contributions, is a fundamental ideal of modern societies. The key focus of societal efforts to ensure socioeconomic mobility has been on the provision of educational opportunities. We review evidence that even with the same education and job opportunities, being born into a poorer family undermines socioeconomic mobility due to processes occurring within organizations. The burden of poorer background might, ceteris paribus, be economically comparable to the gender gap. We argue that in the societal and scientific effort to promote socioeconomic mobility, the key context in which mobility is supposed to happen—organizations—as well as the key part of the life of people striving toward socioeconomic advancement—that as working adults—have been overlooked. We integrate the organizational literature pointing to key within-organizational processes impacting objective (socioeconomic) success with research, some emergent in organizational sciences and some disciplinary, on when, why, and how people from poorer backgrounds behave or are treated by others in the relevant situations. Integrating these literatures generates a novel and useful framework for identifying issues people born into poorer families face as employees, systematizes extant evidence and makes it more accessible to organizational scientists, and allows us to lay the agenda for future organizational scholarshi

Comparison of the effectiveness of two CPR techniques through the use of predictive metrics and the measurement of regional blood flows

Bystander CPR has been recognized as an important link in improving the survival rate for out-of-hospital cardiac arrest. One potential CPR technique for use by bystanders is rhythmic only abdominal compression CPR (OAC-CPR). However, little is known about its strengths and weaknesses relative to continuous chest compression CPR (CC-CPR). In this study, intrasubject comparisons between OAC-CPR and CC-CPR were made during two minute intervals of fibrillation. Predictive metrics of survival and neurological outcome were monitored. No significant difference in the cardiac output between the two techniques was found, while OAC-CPR produced greater blood oxygenation and no abdominal damage over short periods of application. However, OAC-CPR also produced lower carotid flow, and resulted in a greater time from a successful defibrillation until strong heartbeats were observed. End-tidal CO2 measurements suggest that this rate and force combination creates arterial hypocapnia, perhaps causing coronary and cerebral vasoconstriction. For a more detailed observation of the techniques, regional blood flow measurements using a microsphere deposition technique were made. This indicated that OAC-CPR produced lower coronary and cerebral blood flows. As such, OAC-CPR is not recommended for use by bystanders in its current form. Future work will need to center on the refinement of a mathematical model of the technique that incorporates all relevant cardiovascular effects that the technique may experience. From this refined model, a more optimal form of OAC-CPR may be able to be developed and tested in-vivo. As a low risk of regurgitation and abdominal damage was observed for OAC-CPR in this study, its use as circulatory support during cardiac arrest in patients that have recently undergone open heart surgery remains promising

Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner

Insulin resistance creates an environment that promotes β-cell failure and development of diabetes. Understanding the events that lead from insulin resistance to diabetes is necessary for development of effective preventional and interventional strategies, and model systems that reflect the pathophysiology of disease progression are an important component toward this end. We have confirmed that insulin enhances glucose uptake in zebrafish skeletal muscle and have developed a zebrafish model of skeletal muscle insulin resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted insulin signaling and glucose uptake in the skeletal muscle, confirming insulin resistance. In young animals, we observed an increase in the number of β-cells and normal glucose tolerance that was indicative of compensation for insulin resistance. In older animals, the β-cell mass was reduced to that of control with the appearance of impaired glucose clearance but no elevation in fasting blood glucose. Combined with overnutrition, the insulin-resistant animals have an increased fasting blood glucose compared with the control animals, demonstrating that the β-cells in the insulin-resistant fish are in a vulnerable state. The relatively slow progression from insulin resistance to glucose intolerance in this model system has the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets

Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner

Insulin resistance creates an environment that promotes β-cell failure and development of diabetes. Understanding the events that lead from insulin resistance to diabetes is necessary for development of effective preventional and interventional strategies, and model systems that reflect the pathophysiology of disease progression are an important component toward this end. We have confirmed that insulin enhances glucose uptake in zebrafish skeletal muscle and have developed a zebrafish model of skeletal muscle insulin resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted insulin signaling and glucose uptake in the skeletal muscle, confirming insulin resistance. In young animals, we observed an increase in the number of β-cells and normal glucose tolerance that was indicative of compensation for insulin resistance. In older animals, the β-cell mass was reduced to that of control with the appearance of impaired glucose clearance but no elevation in fasting blood glucose. Combined with overnutrition, the insulin-resistant animals have an increased fasting blood glucose compared with the control animals, demonstrating that the β-cells in the insulin-resistant fish are in a vulnerable state. The relatively slow progression from insulin resistance to glucose intolerance in this model system has the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets