Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [H]5-HT, in frontal cortex and the hippocampal region of the human brain

In human cortex and hippocampus area, [³H]5-HT (5 nM) labels 5-HT_1A, 5-HT_1D and 5-HT_1E sites. After masking 5-HT_1A receptors by 0.1 μM 8-OH-DPAT, the binding displaced by 0.1 μM 5-CT presumably represented 5-HT_1D sites and the remaining binding 5-HT_1E sites. In frontal cortex, 5-HT_1A receptors represented the main binding in layers II and VI and a lower fraction on other layers. 5-HT_1D and 5-HT_1E sites, were more homogeneously distributed in layers II to VI (21–34% of specific [³H]5-HT binding). 5-HT_1E sites were of similar affinities (K_D close to 6–8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT_1A receptors represented the major fraction, 5-HT_1D sites a significant fraction and 5-HT_1E a minor fraction of the specific [³H]5-HT binding. In CA3–CA4 fields, 5-HT_1A receptors were less densely present, 5-HT_1D sites were predominant and 5-HT_1E sites represented a significant fraction (27%). The highest densities of 5-HT_1E sites have been measured in subiculum, where 5-HT_1A, 5-HT_1D, and 5-HT_1E binding sites were equally represented and in entorhinal cortex where 5-HT_1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT_1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT_1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT_1E were detected in choroid plexus, where [³H]5-HT was dramatically reduced by mesulergine (5-HT_2C receptors). No significant displacement of [³H]5-HT by mesulergine was measured in other structures.     

Role of double-stranded RNA and Npro of classical swine fever virus in the activation of monocyte-derived dendritic cells

Classical swine fever virus (CSFV) is a noncytopathogenic (ncp) positive-sense RNA virus that replicates in myeloid cells including macrophages and dendritic cells (DC). The virus does not induce type I interferon (IFN-alpha/beta), which in macrophages has been related to the presence of the viral Npro gene. In the present work, the role of viral double-stranded (ds)RNA and Npro in the virus-host cell interaction has been analyzed. Higher levels of detectable dsRNA were produced by a genetically engineered cytopathogenic (cp) CSFV compared with ncp CSFV, and cp CSFV induced IFN-alpha/beta in PK-15 cells. With DC, there was only a small difference in the levels of dsRNA between the cp and ncp viruses, and no IFN-alpha/beta was produced. However, the cp virus induced a higher degree of DC maturation, in terms of CD80/86 and MHC II expression. Npro deletion mutants induced an increase in DC maturation and IFN-alpha/beta production-for both ncp and cp viruses-despite reduced replication efficiency in the DC. Deletion of Npro did not influence dsRNA levels, indicating that the interference was downstream of dsRNA turnover regulation. In conclusion, the capacity of CSFV to replicate in myeloid DC, and prevent IFN-alpha/beta induction and DC maturation, requires both regulated dsRNA levels and the presence of viral Npro.     

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Purpose

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.

Results

Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).

Conclusions

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

     

Emotional Exhaustion and Cognitive Performance in Apparently Healthy Teachers: A Longitudinal Multi‐source Study

We investigate how emotional exhaustion (EE), the core component of burnout, relates to cognitive performance, job performance and health. Cognitive performance was assessed by self‐rated cognitive stress symptoms, self‐rated and peer‐rated cognitive impairments in everyday tasks and a neuropsychological test of learning and memory (LGT‐3); job performance and physical health were gauged by self‐reports. Cross‐sectional linear regression analyses in a sample of 100 teachers confirm that EE is negatively related to cognitive performance as assessed by self‐rating and peer‐rating as well as neuropsychological testing (all p < .05). Longitudinal linear regression analyses confirm similar trends (p < .10) for self‐rated and peer‐rated cognitive performance. Executive control deficits might explain impaired cognitive performance in EE. In longitudinal analyses, EE also significantly predicts physical health. Contrary to our expectations, EE does not affect job performance. When reversed causation is tested, none of the outcome variables at Time 1 predict EE at Time 2. This speaks against cognitive dysfunctioning serving as a vulnerability factor for exhaustion. In sum, results underpin the negative consequences of EE for cognitive performance and health, which are relevant for individuals and organizations alike. In this way, findings might contribute to the understanding of the burnout syndrome. Copyright © 2012 John Wiley & Sons, Ltd.     

Why socially deprived populations have a faster resting heart rate: impact of behaviour, life course anthropometry, and biology--the RECORD Cohort Study

Although studies have shown that resting heart rate (RHR) is predictive of cardiovascular morbidity/mortality, few studies focused on the epidemiology and social aetiology of RHR. Using the RECORD Cohort Study (7158 participants, 2007–2008, Paris region, France), we investigated individual/neighbourhood socioeconomic variables associated with resting heart rate, and assessed which of a number of psychological factors (depression and stress), behaviour (sport-related energy expenditure, medication use, and alcohol, coffee, and tobacco consumption), life course anthropometric factors (body mass index, waist circumference, and leg length as a marker of childhood environmental exposures), and biologic factors (alkaline phosphatase and gamma-glutamyltransferase) contributed to the socioeconomic disadvantage–RHR relationship. Combining individual/neighbourhood socioeconomic factors in a socioeconomic score, RHR increased with socioeconomic disadvantage: +0.9 [95% credible interval (CrI): +0.2, +1.6], +1.8 (95% CrI: +1.0, +2.5), and +3.6 (95% CrI: +2.9, +4.4) bpm for the 3 categories reflecting increasing disadvantage, compared with the lowest disadvantage category. Twenty-one percent of the socioeconomic disadvantage–RHR relationship was explained by sport practise variables, 9% by waist circumference, 7% by gamma-glutamyltransferase, 5% by alkaline phosphatase, and 3% by leg length. Future research should further clarify the mechanisms through which socioeconomic disadvantage influences resting heart rate, as a pathway to social disparities in cardiovascular morbidity/mortality.     

Thoracic endograft positioning and carotid-subclavian bypass grafting in a patient with a saccular aneurysm at the aortic arch

A 75-year-old man was referred to our hospital because of sudden thoracic pain. A saccular aneurysm of the aortic arch extending on the anterior surface of the aortic arch was found on computed tomographic arteriography. The patient was hemodynamically stable and he was programmed for a staged surgical and endovascular approach (hybrid approach). As a first stage and in order to prevent major cardiac complications due to the overstenting of the left subclavian artery (LSA) with the occlusion of the aortocoronary bypass, the patient underwent a polytetrafluoroethylene bypass graft (GORE-TEX, W.L. Gore & Associates, Flagstaff, AZ) between the LSA and the left carotid artery. Intraoperative arteriography revealed a good patency of the left carotid-subclavian bypass and of the left internal mammary bypass on the left anterior descending artery. As a second stage the endovascular procedure was accomplished 5 days later in the operating room. A Gore TAG stent graft (W.L. Gore & Associates) was deployed in the aortic arch 20 mm proximally to the aneurysmatic segment covering the ostium of the LSA. The postoperative course was uneventful and the patient was discharged on the fifth postoperative day in good general conditions. Hybrid procedures for treatment of aneurysms of the aortic arch or of the descending thoracic aorta are a promising alternative to open surgery especially in high-risk patients, with lower early morbidity and mortality rates. Long-term effectiveness remains to be fully elucidated.     

Small-for-menstrual-age infants: Different subgroups detected using individualized fetal growth assessment

Our purpose was to study the individual fetal growth patterns of infants who were born small-for-menstrual-age. Growth in the second and third trimester was assessed in 98 small-for-menstrual-age infants, using individual fetal growth curves generated by the growth model: P = c(t)^k+s(t). Growth indices were compared with those previously reported for that method in infants with normal growth. The small-for-menstrual-age infants were distributed into four growth patterns, ie, infants with either normal or decreased second-trimester growth indices, who, by the time of birth, succeed or fail in fulfilling their individual growth potential. These four growth patterns appear to be associated with different pathophysiological mechanisms and incidences of perinatal complications. Individual fetal growth assessment identifies differences in genetically determined growth and differentiates between fetuses who achieve their growth potential and those with growth failure who are at greater risk for fetal compromise. © 1994 John Wiley & Sons, Inc.     

Emergency air evacuation of patients with acute respiratory failure due to SARS-CoV-2 from Mayotte to Reunion Island

In February 2021, an explosion of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia overwhelmed the only hospital in Mayotte. To report a case series of patients with acute respiratory failure (ARF) due to SARS-CoV-2 who were evacuated by air from Mayotte to Reunion Island.This retrospective observational study evaluated all consecutive patients with ARF due to SARS-CoV-2 who were evacuated by air from Mayotte Hospital to the intensive care unit (ICU) of Félix Guyon University Hospital in Reunion Island between February 2, and March 5, 2021.A total of 43 patients with SARS-CoV-2 pneumonia were evacuated by air, for a total flight time of 2 hours and a total travel time of 6 hours. Of these, 38 patients (88.4%) with a median age of 55 (46–65) years presented with ARF and were hospitalized in our ICU. Fifteen patients were screened for the SARS-CoV-2 501Y.V2 variant, all of whom tested positive. Thirteen patients (34.2%) developed an episode of severe hypoxemia during air transport, and the median paO₂/FiO₂ ratio was lower on ICU admission (140 [102–192] mmHg) than on departure (165 [150–200], P = .022). Factors associated with severe hypoxemia during air transport was lack of treatment with curare (P = .012) and lack of invasive mechanical ventilation (P = .003). Nine patients (23.7%) received veno-venous extracorporeal membrane oxygenation support in our ICU. Seven deaths (18.4%) occurred in hospital.Emergency air evacuation of patients with ARF due to SARS-CoV-2 was associated with severe hypoxemia but remained feasible. In cases of ARF due to SARS-CoV-2 requiring emergency air evacuation, sedated patients receiving invasive mechanical ventilation and curare should be prioritized over nonintubated patients. It is noteworthy that patients with SARS-CoV-2 pneumonia related to the 501Y.V2 variant were very severe despite their young age.