Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.     

Magnetic resonance imaging evaluation of myocardial perfusion and viability in congenital and acquired pediatric heart disease

This study examined the feasibility and potential clinical utility of magnetic resonance imaging (MRI) evaluation of myocardial perfusion (first-pass contrast enhancement) and viability (myocardial delayed enhancement) in 30 patients with congenital and acquired pediatric heart disease. Good agreement was found between MRI evaluation of myocardial perfusion and viability and analysis of segmental wall motion as well as coronary angiography (n = 10) and single photon emission computed tomography (n = 6).     

Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile

Digestive Diseases and Sciences - Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT)...     

Does dystocia during labor pose a risk factor for another non-progressive labor during the subsequent delivery?

Objective: To establish whether failure to progress during labor poses a risk factor for another non-progressive labor (NPL) during the subsequent delivery.

Methods: A retrospective cohort study including singleton pregnancies that failed to progress during the previous labor and resulted in a cesarean section (CS) was conducted. Parturients were classified into three groups for both previous and subsequent labors: CS due to NPL stage I, stage II and an elective CS as a comparison group.

Results: Of 202?462 deliveries, 10?654 women met the inclusion criteria: 3068 women were operated due to NPL stage I and 1218 due to NPL stage II. The comparison group included 6368 women. Using a multivariable logistic regression models, NPL stage I during the previous delivery was found as an independent risk factor for another NPL stage I in the subsequent labor (adjusted odds ratio [OR]?=?2.9; 95% confidence interval [CI]?=?2.4–3.7; p?p?=?0.033; adjusted OR?=?5.3; 95% CI?=?3.7–7.5; p?Conclusion: A previous CS due to a NPL is an independent risk factor for another NPL in the subsequent pregnancy and for recurrent cesarean delivery.     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Problem-based learning in occupational therapy curriculum – implications and challenges

Purpose: Problem-based learning (PBL) is an educational method that fosters self-directed study in small groups. The purpose of this study was to describe the Tel Aviv University’s occupational therapy (OT) program and the challenges implementing such program. In addition, the study compared the PBL grades obtained by students who are native Hebrew speakers with those students who are native Arabic speakers; and, assessed the correlation between the grades in the PBL course and the grades in the clinical fieldwork studies.

Method: 166-second year OT undergraduate students participated. All completed three PBL courses and seven weeks of clinical fieldwork studies. Data collection included students’ grades in PBL course (based on PBL evaluation forms) and in clinical fieldwork studies (based on preceptor’s evaluation and a written assignment).

Results: Pearson correlations revealed significant correlations between PBL grades and clinical fieldwork studies grades. T-test analysis between students who are native Hebrew speakers and those who are native Arabic speakers revealed significant differences in PBL grades.

Conclusions: Findings imply partial congruence between students’ grades in the PBL course and their achievements in the fieldwork studies. Findings might suggest that adjustments should be made in order to assist students from minorities (challenged by language requirements) in gaining higher grades in the PBL program.

• Implications for Rehabilitation

• Problem-Based Learning (PBL) is an educational method, which fosters independent, self-directed study in small groups.

• PBL studies have the potential to prepare students for their clinical experience during studies.

• The PBL program should be adjusted for students from minorities (challenged by language requirements and different cultural backgrounds) in order to assist them in gaining more benefits from the program.

     

Short-term effect of morphine on the thyroid gland in male rats

Experiments were designed to demonstrate that morphine may exert a direct short-term effect on the hormone release of the thyroid gland. Groups of male rats were injected with single doses of 1, 5 and 10 mg/kg morphine, or with 2 mg/kg naloxone and in addition with morphine 30 min after naloxone and/or with naloxone 30 min after morphine pre-treatment. The rats were killed by decapitation 15, 30 and 60 min after the injection and serum was collected and stored for subsequent TSH, T4 and T3 radioassays. All doses of morphine resulted in an increase of serum T4 and T3 concentrations 15 and 30 min after the injection, with a tendency to return to control levels by the 60 min samples. Serum TSH concentrations were to suppressed by administration of 5 and 10 mg/kg but not by 1 mg/kg morphine. Naloxone treatment did not increase the T4 and T3 concentrations; however, serum TSH was elevated in the 15 min sample. Naloxone pre-treatment inhibited the morphine induced release of T4 and T3 into the serum, but naloxone administration after morphine pre-treatment failed to prevent the increase of T4 and T3 secretion. These data suggest that morphine may exert a short-term stimulatory effect on the thyroid gland with a concomitant inhibitory action on the hypothalamo-pituitary TSH system.