CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery.

The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season.

BACKGROUND: The 2017-2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season. METHODS: End-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval. RESULTS: Specimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9-89.2%) observed in children 0.5-14 years old, while all ages VE was 46.6% (95%CI 10.4-68.2%). All ages VE against influenza B was 23.2% (95%CI -10.1-46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017-2018 season. CONCLUSIONS: The moderate-high 2017-2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.

Sudden death in young soldiers. High incidence of syncope prior to death.

During the years 1974 to 1986, 44 young soldiers (mean age 21 +/- 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope.

Cardiovascular changes after bilateral upper dorsal sympathectomy. Short- and long-term effects.

The effect of bilateral upper dorsal sympathectomy (UDS) on cardiac function was investigated in two groups of young healthy patients who underwent bilateral excision of T2 and T3 ganglia for palmar hyperhidrosis. In ten patients echocardiography of left ventricular function (LVF) was performed before operation and 2 weeks after operation. Electrocardiograms (ECG) were done before operation, during operation immediately after sectioning each sympathetic chain, and at 2 weeks after operation. The mean pulse rate decreased significantly in patients after they underwent bilateral UDS. There were no clinical arrhythmias or changes in LVF in any patient. Submaximal exercise testing and ECG tracings done at rest and after effort were obtained for 29 patients before undergoing bilateral UDS, 30 days after operation, and 1-3 more times within a 2-year postoperative period. Pulse rates taken at rest and after effort were significantly lower than those taken after operation, and the blood pressure response to exercise was blunted. ECG tracings showed a significant change in the electrical frontal plane axis and shortening of the QTc interval. These changes were evident 30 days after operation and persisted for 2 years. In conclusion, bilateral UDS has no overt arrhythmogenic effect in the young, healthy heart and its beta-blocker-like effect persists for at least 2 years.