Recent studies demonstrate that the neuropeptide VGF (nonacronymic) is regulated in the hippocampus by antidepressant therapies and animal models of depression and that acute VGF treatment has antidepressant-like activity in animal paradigms. However, the role of VGF in human psychiatric disorders is unknown. We now demonstrate using in situ hybridization that VGF is downregulated in bipolar disorder in the CA region of the hippocampus and Brodmann's area 9 of the prefrontal cortex. The mechanism of VGF in relation to LiCl was explored. Both LiCl intraperitoneally and VGF intracerebroventricularly reduced latency to drink in novelty-induced hypophagia, and LiCl was not effective in VGF ϩ/Ϫ mice, suggesting that VGF may contribute to the effects of LiCl in this behavioral procedure that responds to chronic antidepressant treatment. VGF by intrahippocampal injection also had novel activity in an amphetamine-induced hyperlocomotion assay, thus mimicking the actions of LiCl injected intraperitoneally in a system that phenocopies manic-like behavior. Moreover, VGF ϩ/Ϫ mice exhibited increased locomotion after amphetamine treatment and did not respond to LiCl, suggesting that VGF is required for the effects of LiCl in curbing the response to amphetamine. Finally, VGF delivered intracerebroventricularly in vivo activated the same signaling pathways as LiCl and is necessary for the induction of mitogen-activated protein kinase and Akt by LiCl, thus lending insight into the molecular mechanisms underlying the actions of VGF. The dysregulation of VGF in bipolar disorder as well as the behavioral effects of the neuropeptide similar to LiCl suggests that VGF may underlie the pathophysiology of bipolar disorder.
Disclaimer: Due to the rapidly evolving nature of this outbreak, and in the interests of rapid dissemination of reliable, actionable information, this paper went through expedited peer review. Additionally, information should be considered current only at the time of publication and may evolve as the science develops. Dear Editor: It was 4 am when the hospital admitting medicine service phone rang. "Ten patients with suspected COVID-19 were sent from a nursing home; it's possible that they all may need intensive care unit [ICU] beds. How many beds are available right now?" I will never forget the series of events that followed. The urgency was palpable as evidenced by the frenzy of navigating the emergency department, careful donning and doffing of personal protective equipment, and rapid-fire triaging of each patient. It was 6 am when several more patients from that same nursing home arrived. The nasal cannulas turned into non-rebreathers, which quickly transitioned to high-flow nasal cannulas. The next obvious step was intubation. But one question persisted in our minds: "Are we doing the right thing?"
Coronavirus 2019 (COVID-19) has been reported to trigger Guillain–Barré syndrome (GBS). While uncommon, recurrent GBS (rGBS) episodes, triggered by antecedent viral infections, have been reported in a small proportion of GBS patients, here we describe a patient with a recurrent case of GBS, occurring secondary to COVID-19 infection. Before this patient’s episode, he had two prior GBS flares, each precipitated by a viral infection followed by complete recovery besides intermittent paresthesias. We also consider the nosology of this illness in the spectrum of rGBS and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with their differing natural histories, prognosis, and therapeutic approaches. For patients who have a history of inflammatory demyelinating polyradiculopathies who develop COVID-19, we recommend close observation for neurologic symptoms over the next days and weeks.
Myosin heavy chain (MHC) is a large, multidomain protein important for both cellular structure and contraction. To examine the functional role of two C-terminal domains, the end of the coiled-coil rod and the nonhelical tailpiece, we have generated constructs in which residues within these domains are removed or mutated, and examined their behavior in Caenorhabditis elegans striated muscle. Genetic tests demonstrate that MHC lacking only tailpiece residues is competent to support the timely onset of embryonic contractions, and therefore viability, in animals lacking full-length MHC. Antibody staining experiments show that this truncated molecule localizes as wild type in early stages of development, but may be defective in processes important for thick filament organization later in embryogenesis. Ultrastructural analysis reveals thick filaments of normal morphology in disorganized arrangement, as well as occasional abnormal assemblages. In contrast, molecules in which the four terminal residues of the coiled coil are absent or mutated fail to rescue animals lacking endogenous MHC. Loss of these four residues is associated with delayed protein localization and delayed contractile function during early embryogenesis. Our results suggest that these two MHC domains, the rod and the tailpiece, are required for distinct steps during muscle development.
Acute suppurative thyroiditis (AST) is an uncommon, potentially life-threatening cause of a rapidly enlarging neck mass. It may present similarly to subacute thyroiditis, a relatively benign and self-limiting condition. We report a case of AST in an adult intravenous (IV) drug user with a preexisting goiter who presented with a left forearm abscess that grew methicillin-sensitive Staphylococcus aureus. In this particular case, clinical suspicion for AST was high. As a result, early IV antibiotic therapy was initiated, and this led to rapid clinical improvement furthermore preventing airway compromise. To our knowledge, this is the first case of AST in the literature resulting from likely hematogenous spread in the setting of IV drug use and a preexisting goiter. Overall, this case highlights the importance of assessing risk factors for AST in patients whose presentations may seem more typical of subacute thyroiditis. Such an approach will lead to timely diagnosis and treatment to avoid potentially devastating consequences.
The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome-coronavirus-2, has claimed 5,587,549 lives worldwide as of January 20, 2022. Fortunately, large-scale vaccination can mitigate the impact of COVID-19 by making the disease milder and less common. Although 75.2% of the United States population has received at least 1 dose of a COVID-19 vaccines thus far, concerns regarding vaccine side effects have contributed to vaccine hesitancy. Furthermore, nearly 50% of adults in the United States are concerned not only about side effects, but about their downstream impact, including missed work.The goal of this cross-sectional study was to investigate the effect of messenger RNA vaccine adverse effects on the propensity to miss work among employees associated with a single, large academic health center.Using Qualtrics, all employees, including faculty, staff, and trainees, of 5 large departments were surveyed to determine whether they received the COVID-19 vaccine and which type, and any symptoms they experienced after receipt of either vaccine dose. We hypothesized that vaccine recipients would be more likely to miss work or feel sick enough to miss work following the second dose.Thirty-seven percent of respondents experienced events severe enough that they needed to miss work from either of the doses, with the majority (27.8%) related to the second dose. These findings are consistent with and expand on the results from the phase 3 trials for Pfizer-BionTech and Moderna, which showed that vaccine side effects were more common after the second dose than after the first dose. Our statistically significant finding was more common among Asians, women, trainees/house staff, and nonphysician clinical employees.With an increasing number of individuals taking the vaccine, employers will need to account for the impact of adverse effects on their employees’ ability to work. These findings will further help organizations better plan for staffing as vaccinations increase to mitigate the spread of COVID-19.
Objective Diabetic preventative health maintenance involves (1) adherence to guidelines and (2) appropriate documentation. This study evaluates the frequency with which internal medicine (IM) residents met these two outcomes. We also evaluated if there were differences in outcomes between resident classes. Methods In this retrospective analysis, 234 diabetic outpatient visits were analyzed. Guidelines were derived from the American Diabetes Association (ADA). The outcomes for each guideline were averaged and stratified by resident class. Averages within and between classes were compared using the student's paired t-test and one-way ANOVA respectively. Results Classes were most adherent to A1c testing guidelines (PGY-1 96.1%, PGY-2 97.6%, and PGY-3 95.9%). PGY-1 and PGY-2 classes were least adherent to podiatry (27.5% and 17.6% respectively), whereas PGY-3 had equal least adherence rates to podiatry and lifestyle modification guidelines (36.7%). All classes had highest rates in documenting A1c findings (PGY-1 92.2%, PGY-2 97.6%, and PGY-3 85.7%) and lowest rates in documenting relevant podiatry information (PGY-1 5.9%, PGY-2 5.9%, and PGY-3 11.2%). Comparing sequential resident classes, there was a decline in lifestyle counselling and documentation from PGY-1 to PGY-2. From PGY-2 to PGY-3, there was improvement in adherence to statin, podiatry, microalbuminuria, and monofilament guidelines. There was also improvement in documenting statin and monofilament usage, however, A1c reporting declined. Conclusion The findings of the study suggest disproportionate levels of care in diabetes preventative management. Additionally, program directors should take caution in assuming linear improvement with sequential resident classes.
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