BACKGROUND Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.OBJECTIVES The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.METHODS We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.RESULTS Among 700 patients (mean age 50 6 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.CONCLUSION Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
Kappa-opioid receptors (KORs) are important for motivation and other medial prefrontal cortex (mPFC)-dependent behaviors. Although KORs are present in the mPFC, their role in regulating transmission in this brain region and their contribution to KOR-mediated aversion are not known. Using in vivo microdialysis in rats and mice, we demonstrate that intra-mPFC administration of the selective KOR agonist U69,593 decreased local dopamine (DA) overflow, while reverse dialysis of the KOR antagonist nor-Binaltorphimine (nor-BNI) enhanced mPFC DA overflow. Extracellular amino-acid levels were also affected by KORs, as U69,593 reduced glutamate and GABA levels driven by the glutamate reuptake blocker, l-trans-pyrrolidine-2,4-dicarboxylate. Whole-cell recordings from mPFC layer V pyramidal neurons revealed that U69,593 decreased the frequency, but not amplitude, of glutamatergic mini EPSPs. To determine whether KOR regulation of mPFC DA overflow was mediated by KOR on DA terminals, we utilized a Cre recombinase-driven mouse line lacking KOR in DA neurons. In these mice, basal DA release or uptake was unaltered relative to controls, but attenuation of mPFC DA overflow by local U69,593 was not observed, indicating KOR acts directly on mPFC DA terminals to locally inhibit DA levels. Conditioning procedures were then used to determine whether mPFC KOR signaling was necessary for KOR-mediated aversion. U69,593-mediated conditioned place aversion was blocked by intra-mPFC nor-BNI microinjection. These findings demonstrate that mPFC KORs negatively regulate DA and amino-acid neurotransmission, and are necessary for KOR-mediated aversion.
Protein kinase C interacting protein/histidine triad nucleotide binding protein 1 (PKCI/HINT1) is a member of the histidine triad protein family. Although this protein is widely expressed in the mammalian brain including mesocorticolimbic and mesostriatal regions, its physiological function in CNS remains unknown. Recent microarray studies reported decreased mRNA expression of PKCI/HINT1 in the frontal cortex of individuals with schizophrenia, suggesting the possible involvement of this protein in the pathophysiology of the disease. In view of the documented link between dopamine (DA) transmission and schizophrenia, the present study used behavioral and neurochemical approaches to examine the influence of constitutive PKCI/HINT1 deletion upon: (i) basal and amphetamine (AMPH)-evoked locomotor activity; (ii) DA dynamics in the dorsal striatum, and (iii) postsynaptic DA receptor function. PKCI/HINT1À/À (KO) mice displayed lower spontaneous locomotion relative to wild-type (WT) controls. Acute AMPH administration significantly increased locomotor activity in WT mice; nonetheless, the effect was enhanced in KO mice. Quantitative microdialysis studies revealed no alteration in basal DA dynamics in the striatum or nucleus accumbens of KO mice. The ability of acute AMPH to increase DA levels was unaltered indicating that function in presynaptic DA neurotransmission in these regions do not underlie the behavioral phenotype of KO mice. In contrast to WT mice, systemic administration of the direct-acting DA receptor agonist apomorphine (10 mg/kg) significantly increased locomotor activity in KO mice suggesting that postsynaptic DA function is altered in these animals. These results demonstrate an important role of PKCI/HINT1 in modulating the behavioral response to AMPH. Furthermore, they indicate that the absence of this protein may be associated with dysregulation of postsynaptic DA transmission.
Background Naturally occurring carbon and nitrogen stable isotope ratios [13C/12C (CIR) and 15N/14N (NIR)] are promising dietary biomarkers. As these candidate biomarkers have long tissue residence times, long-term feeding studies are needed for their evaluation. Objective Our aim was to evaluate plasma, RBCs, and hair CIR and NIR as biomarkers of fish, meat, and sugar-sweetened beverage (SSB) intake in a 12-wk dietary intervention. Methods Thirty-two men (aged 46.2 ± 10.5 y; BMI: 27.2 ± 4.0 kg/m2) underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Phoenix, Arizona. The effects of fish, meat, and SSB intake on CIR and NIR were evaluated using a balanced factorial design, with each intake factor at 2 levels (present/absent) in a common, background diet (50% carbohydrate, 30% fat, 20% protein). Fasting blood samples were taken biweekly from baseline, and hair samples were collected at baseline and postintervention. Data were analyzed using multivariable regression. Results The postintervention CIR of plasma was elevated when diets included meat (β = 0.89, 95% CI: 0.73,1.05) and SSBs (β = 0.48, 95% CI: 0.32, 0.64). The postintervention NIR of plasma was elevated when diets included fish (β = 0.85, 95% CI: 0.64, 1.05) and meat (β = 0.61, 95% CI: 0.42, 0.8). Results were similar for RBCs and hair. Postintervention RBC CIR and NIR had strong associations with baseline, suggesting that turnover to the intervention diets was incomplete after 12 wk. Estimates of isotopic turnover rate further confirmed incomplete turnover of RBCs. Conclusions CIR was associated with meat and SSBs, and more strongly with meat. NIR was associated with fish and meat, and more strongly with fish. Overall, CIR and NIR discriminated between dietary fish and meat, and to a lesser extent SSBs, indicating their potential utility as biomarkers of intake in US diets. Approaches to make these biomarkers more specific are needed. This trial was registered at clinicaltrials.gov as NCT01237093.
A common complication of sinus augmentation is perforation of the sinus membrane during augmentation and/or implant placement. This retrospective study examines the effect of sinus membrane perforation with regard to graft survival and implant integration. A total of 175 sinuses were augmented with 115 of the membranes being reported intact at the time of surgery. A total of three infections occurred in patients who sustained perforated sinuses and one infection occurred in a patient who had an intact sinus. All four infections resolved after culture sensitivity and placement of the patient on an appropriate antibiotic for 10 days. Of 438 dental implants placed in the augmented sinuses, five implants failed, four of which were associated with perforated sinuses and and which was not associated with a perforated grafted sinus.
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