Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule remodeling after Serca2 knockout

Cardiomyocyte contraction and relaxation are controlled by Ca(2+) handling, which can be regulated to meet demand. Indeed, major reduction in sarcoplasmic reticulum (SR) function in mice with Serca2 knockout (KO) is compensated by enhanced plasmalemmal Ca(2+) fluxes. Here we investigate whether altered Ca(2+) fluxes are facilitated by reorganization of cardiomyocyte ultrastructure. Hearts were fixed for electron microscopy and enzymatically dissociated for confocal microscopy and electrophysiology. SR relative surface area and volume densities were reduced by 63% and 76%, indicating marked loss and collapse of the free SR in KO. Although overall cardiomyocyte dimensions were unaltered, total surface area was increased. This resulted from increased T-tubule density, as revealed by confocal images. Fourier analysis indicated a maintained organization of transverse T-tubules but an increased presence of longitudinal T-tubules. This demonstrates a remarkable plasticity of the tubular system in the adult myocardium. Immunocytochemical data showed that the newly grown longitudinal T-tubules contained Na(+)/Ca(2+)-exchanger proximal to ryanodine receptors in the SR but did not contain Ca(2+)-channels. Ca(2+) measurements demonstrated a switch from SR-driven to Ca(2+) influx-driven Ca(2+) transients in KO. Still, SR Ca(2+) release constituted 20% of the Ca(2+) transient in KO. Mathematical modeling suggested that Ca(2+) influx via Na(+)/Ca(2+)-exchange in longitudinal T-tubules triggers release from apposing ryanodine receptors in KO, partially compensating for reduced SERCA by allowing for local Ca(2+) release near the myofilaments. T-tubule proliferation occurs without loss of the original ordered transverse orientation and thus constitutes the basis for compensation of the declining SR function without structural disarrangement.     

Effect of AndoSan(™) on expression of adhesion molecules and production of reactive oxygen species in human monocytes and granulocytes in vivo

Abstract Background. Oral intake (60 ml daily) over 12 days in eight healthy volunteers of an immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM (AndoSan(?))), reduced the monocyte and granulocyte release of mainly proinflammatory cytokines in vivo, suggesting an anti-inflammatory effect. In this foremost in vivo study, the aim was to examine the effect of such AndoSan(?) consumption on the expression of adhesion molecules CD11b, CD11c and CD62L and production of reactive oxygen species (ROS) in leukocytes. Methodology/Principal findings. As shown by flow cytometry, there was a significant increase of CD62L expression on monocytes and granulocytes from before (day 0) compared with 12 days after daily AndoSan(?) consumption. However, only minor alterations and no clear trend in the expression of CD11b and CD11c were detected. Intracellular ROS (mainly superoxide ion) were significantly reduced in these cells from days 0 to 12. Conclusions/Significance. These results support that oral intake of AndoSan(?) exhibits an anti-inflammatory effect in humans in vivo.     

Mental health as perceived by persons with mental disorders – an interpretative phenomenological analysis study

In this interpretative phenomenological analysis study, we explored how persons with mental disorders perceive mental health. Adapting a salutogenic theoretical framework, 12 former inpatients were interviewed. The analysis revealed experiences of mental health as a movement, like walking up and down a staircase. Perceived mental health is expressed both verbally in an everyday language and through body language. Mental health is an aspect of being that is always present and which is nourished by four domains of life: the emotional; physical; social and spiritual domains. Mental health is experienced in everyday life as a sense of energy, and as more or less wellbeing. Exploring persons' meanings of mental health from a subjective perspective can extend the knowledge base that can be used in mental health promotion strategies.     

Eating Behavior and Glucagon-Like Peptide-1-Producing Cells in Interposed Ileum and Pancreatic Islets in Rats Subjected to Ileal Interposition Associated with Sleeve Gastrectomy

Background

Ileal interposition–sleeve gastrectomy (II–SG) has been developed as a metabolic surgery based on the hindgut hypothesis. The aim of the present study was to test this hypothesis by studying the eating behavior, metabolic changes, and glucagon-like peptide-1 (GLP-1)-producing cells in rat models.

Methods

Male Sprague–Dawley rats were subjected to laparotomy, II, SG, or II–SG. Eating behavior and metabolic parameters were monitored by an open-circuit indirect calorimeter designed for a comprehensive laboratory animal monitoring system. GLP-1-producing cells were examined by quantitative immunohistochemistry.

Results

After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced, while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory exchange ratio, VCO₂/VO₂, was increased to above 1.0 (i.e., carbohydrate metabolism) during both daytime and nighttime at 2 weeks postoperatively. After SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms of volume density), but not in the ileum (number/mm). After II–SG, the rate of eating was reduced, while meal duration (min) was increased during both daytime and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by about 2.5-fold in the interposed ileum and also increased to the same extent in the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells in the pancreatic islets after SG or II–SG were located around the insulin-producing β cells.

Conclusions

The present study provides evidence supporting the hindgut hypothesis. II–SG increased GLP-1 production both in the interposed ileum and in the pancreatic islets, leading to metabolic beneficial effects and altered eating behavior.     

Risk Factors for Infection after 46,113 Intramedullary Nail Operations in Low- and Middle-income Countries

Background

The fields of surgery and trauma care have largely been neglected in the global health discussion. As a result the idea that surgery is not safe or cost effective in resource-limited settings has gone unchallenged. The SIGN Online Surgical Database (SOSD) is now one of the largest databases on trauma surgery in low- and middle-income countries (LMIC). We wished to examine infection rates and risk factors for infection after IM nail operations in LMIC using this data.

Methods

The SOSD contained 46,722 IM nail surgeries in 58 different LMIC; 46,113 IM nail operations were included for analysis.

Results

The overall follow-up rate was 23.1 %. The overall infection rate was 1.0 %, 0.7 % for humerus, 0.8 % for femur, and 1.5 % for tibia fractures. If only nails with registered follow-up (n = 10,684) were included in analyses, infection rates were 2.9 % for humerus, 3.2 % for femur, and 6.9 % for tibia fractures. Prophylactic antibiotics reduced the risk of infection by 29 %. Operations for non-union had a doubled risk of infection. Risk of infection was reduced with increasing income level of the country.

Conclusions

The overall infection rates were low, and well within acceptable levels, suggesting that it is safe to do IM nailing in low-income countries. The fact that operations for non-union have twice the risk of infection compared to primary fracture surgery further supports the use of IM nailing as the primary treatment for femur fractures in LMIC.     

Sex differences in plaque morphology may explain the higher male prevalence of myocardial infarction compared to angina pectoris. The Tromsø Study

Objectives To study whether the degree of carotid atherosclerosis and the male predominance of echolucent plaques could explain the sex difference in myocardial infarction (MI) compared to angina pectoris (AP).

Design Ultrasound examination of the carotid artery was performed in 6727 persons. The presence of plaque, plaque thickness and number of segments with plaque were recorded. Plaque morphology in terms of echogenicity was scored as echolucent (soft plaque) or echogenic (hard plaque). A questionnaire was used to obtain information about coronary heart disease.

Results In men with the most advanced atherosclerosis, the risk (OR, 95% CI) of having MI compared to those with no carotid atherosclerosis was less than half as the corresponding risk in women (2.2, 1.4–3.3 vs 5.3, 2.6–10.6). For MI, the male-to-female ratio was highest in the group with no carotid plaque and declined by increasing burden of atherosclerosis. For AP, the sex ratio was independent of the degree of atherosclerosis.

Conclusions The findings support the hypothesis that the sex difference in MI compared to AP is due to the higher male prevalence of echolucent plaque.