Effekte von pulsatiler Gabe von Kortisol auf die Hormonsekretion und das Schlaf-EEG bei Patienten mit Depression

Patienten mit depressiven Erkrankungen weisen oft ausgeprägte Veränderugen der Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA) auf, die meist von einem Hyperkortisolismus begleitet sind. Eine häufige Begleiterscheinung von Depressionen sind subjektive und objektive Schlafstörungen. Die Ergebnisse zahlreicher klinischer Studien weisen darauf hin, daß die gestörte Regulation der HPA-Achse eine entscheidende Rolle in der Ätiologie der Depression spielt. Ebenso gibt es eindeutige Hinweise für eine Interaktion von HPA-Achse und der Schlafregulation. Im Hinblick auf mögliche Vulnerabilitätsfaktoren für despressive Erkrankungen nimmt die Veränderung bestimmter Schlafparameter einen wichtigen Platz ein. Kortisol hat charakteristische Effekte auf das Schlaf-EEG und die nächtliche Hormonsekretion bei gesunden Probanden im Sinne einer Stimulierung von Tiefschlaf und Wachstumshormon, dagegen einer Supprimierung von REM-Schlaf (Friess et al., 1994; Bohlhalter et al., 1997). Die in der voliegenden Arbeit dokumentierte Dissoziation zwischen Hydrokortison induzierter Stimulierbarkeit von Tiefschlaf und Wachstumshormon bezogen auf den Suppressionstatus der HPA-Achse ist eine bisher nicht beschriebene Beobachtung. Warum die Tiefschlafantwort bei Vorliegen einer Überfunktion der HPA-Achse ausblieb, läßt sich wie oben ausführlich diskutiert nicht letztlich klären. Die Befunde dieser Studie zeigen, daß körpereigene wie auch exogen applizierte Kortikoide spezifische Effekte auf das zentrale Nervensystem ausüben und liefern damit Hinweise für eine zentrale Beteiligung der Kortikoide an der gemeinsamen Regulation von endokriner Aktivität und Schlafverhalten. Diese Ergebnisse liefern weitere Hinweise für eine bidirektionale Interaktion zwischen Schlafregulation und hormonellem Funktionsstatus

Emphysema and secondary pneumothorax in young adults smoking cannabis

Background: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. Study design: Retrospective case series. Methods: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). Results: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p = 0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. Conclusions: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the futur

The European Forest and Agriculture Optimisation Model -- EUFASOM

Land use is a key factor to social wellbeing and has become a major component in political negotiations. This paper describes the mathematical structure of the European Forest and Agricultural Sector Optimization Model. The model represents simultaneously observed resource and technological heterogeneity, global commodity markets, and multiple environmental qualities. Land scarcity and land competition between traditional agriculture, forests, nature reserves, pastures, and bioenergy plantations is explicitly captured. Environmental change, technological progress, and policies can be investigated in parallel. The model is well-suited to estimate competitive economic potentials of land based mitigation, leakage, and synergies and trade-offs between multiple environmental objectives.Land Use Change Optimization, Resource Scarcity, Market Competition, Welfare Maximization, Bottom-up Partial Equilibrium Analysis, Agricultural Externality Mitigation, Forest Dynamics, Global Change Adaptation, Environmental Policy Simulation, Integrated Assessment, Mathematical Programming, GAMS

Behandlungsempfehlungen Insomnie der Gruppe «Schlaf & Psychiatrie» der SGSSC

Die Insomnie ist eine häufige Störung der Schlaf-Wach-Regulation und tritt oft komorbid auf. Die nachfolgenden Behandlungsempfehlungen stellen evidenzbasierte Diagnostik- und Therapiestrategien vor und umfassen sowohl psychotherapeutische wie auch pharmakotherapeutische Interventionen. Diese Empfehlungen der Schweizerischen Gesellschaft für Schlafforschung, Schlafmedizin und Chronobiologie (SGSSC) für die Behandlung der Insomnie wurden auf Grundlage der Leitlinien der «European Sleep Research Society» (ESRS) von 2023 [1] sowie der S3-Leitlinie/Nationalen Versorgungsleitlinie «Nicht erholsamer Schlaf/Schlafstörungen» der Deutschen Gesellschaft für Schlafforschung und Schlafmedizin (DGSM) von 2017 [2] erstellt. Sie geben nicht unbedingt die Ansicht der SMF-Redaktion wieder. Der Inhalt untersteht der redaktionellen Verantwortung der unterzeichnenden Fachgesellschaft bzw. Arbeitsgruppe

RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

BACKGROUND: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. METHODS: In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. RESULTS: The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. CONCLUSION: Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Climate-Relevant Ocean Transport Measurements in the Atlantic and Arctic Oceans

Ocean circulation redistributes heat, freshwater, carbon, and nutrients all around the globe. Because of their importance in regulating climate, weather, extreme events, sea level, fisheries, and ecosystems, large-scale ocean currents should be monitored continuously. The Atlantic is unique as the only ocean basin where heat is, on average, transported northward in both hemispheres as part of the Atlantic Meridional Overturning Circulation (AMOC). The largely unrestricted connection with the Arctic and Southern Oceans allows ocean currents to exchange heat, freshwater, and other properties with polar latitudes

Emphysema and secondary pneumothorax in young adults smoking cannabis

BACKGROUND: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. STUDY DESIGN: Retrospective case series. METHODS: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). RESULTS: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. CONCLUSIONS: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future