Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation-free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes.

A common variant of PNPLA3 (p.I148M) is not associated with alcoholic chronic pancreatitis

Background Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a common PNPLA3 variant (p.I148M) is associated with the development of alcoholic liver cirrhosis (ALC). Since, alcoholic CP and ALC share the same aetiology PNPLA3 variant (p.I148M) possibly influences the development of alcoholic CP. Methods Using melting curve analysis we genotyped the variant in 1510 patients with pancreatitis or liver disease (961 German and Dutch alcoholic CP patients, 414 German patients with idiopathic or hereditary CP, and 135 patients with ALC). In addition, we included in total 2781 healthy controls in the study. Results The previously published overrepresentation of GG-genotype was replicated in our cohort of ALC (p-value <0.0001, OR 2.3, 95% CI 1.6–3.3). Distributions of genotype and allele frequencies of the p.I148M variant were comparable in patients with alcoholic CP, idiopathic and hereditary CP and in healthy controls. Conclusions The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis.

Facing the dreaded: does mindfulness facilitate coping with distressing experiences? A moderator analysis

Increasing evidence shows that mindfulness is positively related to mental health; however, the nature of this relationship is not fully understood. The current study used structural equation modeling to investigate the hypothesis that mindfulness moderates the association between the occurrence of unavoidable distressing experiences (UDE) and mental health. Participants from a community sample (N = 376) completed the Freiburg Mindfulness Inventory, the Positive and Negative Affect Scale, the Brief Symptom Inventory, the Inventory of Approach and Avoidance Motivation, and the Incongruence Scale. Results indicated that mindfulness moderated the association between unavoidable distressing events and psychopathological symptoms/negative affect. Thus, mindfulness may contribute to enhance the ability to cope with UDE and thus mitigate the detrimental effects of these experiences on mental health.

Demografie

Demografie Marcel Zwahlen, Matthias Egger, Johannes Siegrist Die Frage „Wie viele sind wir?“ bewegt Regierungen bereits seit dem Altertum. Sie bildet die Grundlage der Demografie [von démos (gr.): Volk und grafé (gr.): Schrift, Beschreibung], die sich mit verschiedenen Merkmalen von Bevölkerungen beschäftigt. Dabei interessieren neben der Gesamtgröße der Bevölkerung, ihrer altersmäßigen Zusammensetzung und ihrer geografischen Verteilung auch die sozialen und Umweltfaktoren, die hier für Veränderungen verantwortlich sind. Die Daten zur fortlaufenden Beschreibung der Bevölkerung stammen mehrheitlich aus staatlichen Quellen, v. a. aus Volkszählungen, dem Geburten- und Sterberegister sowie repräsentativen Stichproben-Erhebungen. In diesem Abschnitt beschäftigen wir uns mit den Kennziffern, die DemografInnen zur Beschreibung einer Bevölkerung verwenden, z. B. dem Geburtenüberschuss, dem Wanderungssaldo, verschiedenen Sterberaten, der Lebenserwartung und potentiell verlorenen Lebensjahren. Abschließend betrachten wir häufig verwendete grafische Darstellungen, z. B. zur Altersstruktur einer Bevölkerung und erläutern zeitliche Trends in West- und Ostdeutschland sowie in der Schweiz. Schweizerische Lernziele: CPH 17–20

Herz-Kreislauf-Krankheiten

Rund ein Drittel der weltweiten Todesfälle sind auf Herz-Kreislauf-Krankheiten zurückzuführen. In den industrialisierten Ländern sind sie die häufigste Todesursache. Den größten Anteil hat dabei die koronare Herzkrankheit, gefolgt vom Schlaganfall und der Herzinsuffizienz. In westlichen Industrienationen dürfte jede zweite Person im Lauf ihres Lebens an Herz-Kreislauf-Krankheiten erkranken. Da das Risiko mit zunehmendem Alter zunimmt, wird die Anzahl von Herz-Kreislauf- Erkrankungen aufgrund der demografischen Entwicklung in Zukunft weiter ansteigen. In diesem Abschnitt betrachten wir zuerst die epidemiologische Bedeutung der Herz-Kreislauf-Krankheiten und schauen hier insbesondere auf die globale Bedeutung, die geografischen Unterschiede sowie die sich derzeit entwickelnden zeitlichen Trends. Anschließend erörtern wir, welche Risikofaktoren zur Entstehung von Herz-Kreislauf-Krankheiten beitragen und mit welchen präventiven Maßnahmen diese Erkrankungen zu verhindern sind. Schweizerische Lernziele: CPH 34–35, CPH 37, CPH 40–41

Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease

In Switzerland, the first course of intravenous steroids for treatment of episodes of demyelinating CNS disease is usually administered in an inpatient setting. We prospectively evaluated short term tolerance of treatment with special emphasis on sleep quality.

Cross-sectional observational study of 208 patients with non-classical urea cycle disorders

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial.