Microvascular endothelial dysfunction in heart failure patients: An indication for exercise treatment?

BACKGROUND: Endothelial dysfunction represents a diagnostic marker to differentiate disease severity in chronic heart failure (CHF) patients. Retinal vessel phenotyping was applied in CHF patients as it has been acknowledged as a sensitive diagnostic tool to quantify microvascular health and overall cardiovascular risk. METHODS: The central retinal arteriolar (CRAE) and venular diameter equivalents (CRVE) as well as the retinal microvascular function, quantified by arteriolar (aFID) and venular flicker-light induced dilatation (vFID), were analyzed in 26 CHF patients. These data were compared with 26 age- and sex-matched healthy peers. The effects of an exercise intervention on retinal microvascular health in one CHF patient were investigated to demonstrate potentially beneficial effects of exercise treatment in a case report format as proof of concept. RESULTS: CHF patients showed narrower CRAE (170 ± 16 µm vs. 176 ± 16 µm, p = 0.237) and wider CRVE (217 ± 20 µm vs. 210 ± 17 µm, p = 0.152), resulting in a significantly lower arteriolar-to-venular diameter ratio (AVR, 0.79 ± 0.07 vs. 0.84 ± 0.06, p = 0.004) compared to controls. More strikingly, CHF patients showed significantly lower mean aFID (1.24 ± 1.14% vs. 3.78 ± 1.85%, p < 0.001) and vFID (2.89 ± 1.33% vs. 3.88 ± 1.83%, p = 0.033). Twelve weeks of exercise therapy induced wider CRAE (143 ± 1.0 µm vs. 153 ± 0.9 µm), narrower CRVE (183 ± 3.1 µm vs. 180 ± 2.4 µm) and improved aFID (0.67% vs. 1.25%) in a male 78 years old CHF patient. CONCLUSIONS: aFID is a sensitive diagnostic tool to quantify microvascular impairments in CHF patients. Exercise treatment in CHF patients has high potential to improve retinal microvascular health as a marker for vascular regeneration and overall risk reduction, which warrants further examination by randomized controlled trials.

Has Being Lost While High-Altitude Mountaineering Become Less Frequent? A Retrospective Analysis from the Swiss Alps.

BACKGROUND: High-altitude mountaineering is becoming more popular. Despite technical developments such as global positioning systems, mountaineers still lose their way. This study aimed to analyze characteristics of alpinists that lost their way while high-altitude mountaineering in Switzerland. MATERIAL AND METHODS: Data from the central registry of the Swiss Alpine Club between 2009 and 2020 were retrospectively analyzed. Changes in the number of cases and severity of injuries over time were examined using simple linear regression models. Descriptive analyses were performed for age, time of emergency occurrence, and factors associated with being lost. The Mann-Whitney U test assessed between-sex comparisons. RESULTS: Of the 4596 emergency cases during the observation period, 275 cases (5.9%) were due to being lost (76.4% male). A mean of 22.9 ± 9.6 cases per year was detected. The number of cases did not change significantly over time. Similarly, this was the case for the NACA-Score (National Advisory Committee for Aeronautics Score) with the majority of mountaineers remaining uninjured (77.8%). The median age was 42 (35-54) years for the full sample and 45 (35-56) years and 40 (33-48) years for males and females, respectively. Fog or weather changes, exhaustion, and inadequate tour planning (time and darkness) were frequently documented by rescuers as perceived reasons for being lost. Regarding the time of emergency occurrence, three peaks were detected, around 10 am, 5 pm, and 8 pm. CONCLUSIONS: Our findings show that the number of emergencies due to being lost was stable during the 12-year period. Furthermore, we presented factors that might be associated with losing one's way during mountaineering. These results may form an important basis for future studies determining risk factors for being lost and the prevention of such emergencies.

How Is CYP17A1 Activity Altered in Autism? A Pilot Study to Identify Potential Pharmacological Targets.

Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m2, age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m2, 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m2, age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m2, age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11ß-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism.

[Accidents with Animals While Hiking in the Swiss Alps]. / Bienen, Wespen, Schlangen ­ eine retrospektive Analyse von Unfällen mit Tieren beim Bergwandern in den Schweizer Alpen.

Accidents with Animals While Hiking in the Swiss Alps Abstract. Mountain hiking is very popular. However, despite potential benefits, there are risks, also by animals. Retrospectively, all mountain hiking emergencies (n = 10 185) from the years 2009-2018 were analyzed using the registry of the Swiss Alpine Club (SAC), with 104 mountain emergencies caused by animals. The average NACA score was 3.2 ± 1.6, and more than half of the mountain emergencies had a NACA score >4, which can be associated with a life-threatening condition. More than half of the emergencies were caused by insects (bees, wasps, bumblebees, hornets), and just under a quarter each by hoofed animals and snakes, respectively. Three of these events were mortal, and all of these were caused by hoofed animals (mother cow herd, horse, bull). Therefore, it is recommended to keep a safe distance from these animals when passing them.

Stress-induced alterations of social behavior are reversible by antagonism of steroid hormones in C57/BL6 mice.

Various disturbances of social behavior, such as autism, depression, or posttraumatic stress disorder, have been associated with an altered steroid hormone homeostasis and a dysregulation of the hypothalamus-pituitary-adrenal axis. A link between steroid hormone antagonists and the treatment of stress-related conditions has been suggested. We evaluated the effects of stress induction on social behavior in the three chambers and its potential reversibility upon specific steroid hormone antagonism in mice. C57BL/6 mice were stressed twice daily for 8 days by chronic swim testing. Social behavior was evaluated by measuring, first, the preference for sociability and, second, the preference for social novelty in the three-chamber approach before and after the chronic swim test. The reversibility of behavior upon stress induction was analyzed after applying steroid hormone antagonists targeting glucocorticoids with etomidate, mineralocorticoids with potassium canrenoate, and androgens with cyproterone acetate and metformin. In the chronic swim test, increased floating time from 0.8 ± 0.2 min up to 4.8 ± 0.25 min was detected (p < 0.01). In the three-chamber approach, increased preference for sociability and decreased preference for social novelty was detected pre- versus post-stress induction. These alterations of social behavior were barely affected by etomidate and potassium canrenoate, whereas the two androgen antagonists metformin and cyproterone acetate restored social behavior even beyond baseline conditions. The alteration of social behavior was better reversed by the androgen as compared with the glucocorticoid and mineralocorticoid antagonists. This suggests that social behavior is primarily controlled by androgen rather than by glucocorticoid or mineralocorticoid action. The stress-induced changes in preference for sociability are incompletely explained by steroid hormone action alone. As the best response was related to metformin, an effect via glucose levels might confound the results and should be subject to future research.

Are Steroid Hormones Dysregulated in Autistic Girls?

Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism.

Steroid Metabolites Support Evidence of Autism as a Spectrum.

Objectives: It is common nowadays to refer to autism as a spectrum. Increased evidence of the involvement of steroid metabolites has been shown by the presence of stronger alterations in Kanner's syndrome compared with Asperger syndrome. Methods: 24 h urine samples were collected from 20 boys with Asperger syndrome, 21 boys with Kanner's syndrome, and identically sized control groups, each matched for age, weight, and height for comprehensive steroid hormone metabolite analysis via gas chromatography-mass spectrometry. Results: Higher levels of most steroid metabolites were detected in boys with Kanner's syndrome and Asperger syndrome compared to their matched controls. These differences were more pronounced in affected individuals with Kanner's syndrome versus Asperger syndrome. Furthermore, a specific and unique pattern of alteration of androsterone, etiocholanolone, progesterone, tetrahydrocortisone, and tetrahydrocortisol was identified in boys with Kanner's syndrome and Asperger syndrome. Interestingly, in both matched samples, only androsterone, etiocholanolone, progesterone, tetrahydrocortisone, tetrahydrocortisol, and 5a-tetrahydrocortisol groups were positively correlated. In the Asperger syndrome group, all metabolites showed a positive correlation. In the Kanner's syndrome group, 5-a tetrahydrocortisol with androsterone showed a positive correlation. Conclusions: Due to differences in the level of alteration, the premise that Asperger syndrome is on the mild side of the autism spectrum and that Kanner's syndrome is on the severe side is supported, but alteration patterns yield different phenotypic expressions.

[Patrouille des Glaciers - Analysis of Course Times]. / Laufzeitenanalyse der Patrouille des Glaciers (PDG) ­ Wie sind die Leistungsanforderungen zu taxieren?

Background Backcountry skiing has become more and more popular. The development of skis and equipment has been impressive and suggests that achieving a good performance level is much easier today than it was in the past. Taking the most popular backcountry skiing race in Switzerland, the "Patrouille des Glaciers (PDG)", we addressed the question as to whether this development has led to faster course times over the past ten years and what recommendations can be made for participants. Methods The average course times for the original course Zermatt - Arolla - Verbier were calculated over the past ten years for two cohorts (top-ten and median), separated by category. Results Contrary to expectations, a tendency towards an increase of average course times was detected over the past ten years. The majority of participants need about 12 hours to complete the whole course, which indicates the high overall performance level of PDG skiers. Furthermore, it is assumed that the optimal age for such ultra-performances is around 40. Discussion Due to the increasing demand to participate, it is assumed that organisers tend to admit an ever larger number of alpinists for participation. In consequence, the race is attended by more and more leisure athletes, leading to an increase of average course times over the past ten years. Nevertheless, the majority of participants only need about 12 hours for the whole course of 110 performance kilometres, which requires adequate training. This should be kept in mind by those who consider taking part.

[Analysis of Cardiovascular Risk Factors in Young Backcountry Skiers in the Gotthard Region]. / Analyse kardiovaskulärer Risikofaktoren bei jugendlichen Skitourengängern im Gotthardgebiet.

Background and Objectives Although the frequency of cardiovascular events, especially the end manifestation of myocardial infarction, has decreased in recent years, cardiovascular disease continues to be one of the most frequent illnesses. Also it is known that the cardiac system sustains more stress at high altitudes than it does at intermediate altitudes. This leads to the question if young alpinists should undergo cardiac evaluation before setting out for a trip to the Himalayas or the Andes Mountains. Material and Methods This study analysed 86 young male, active backcountry skiers (26 ±â€Š8.9 years) in the Swiss Alps (Gotthard area) for cardiovascular risk factors (diabetes mellitus, obesity, smoking, lack of physical activity) and cardiovascular diseases (coronary heart disease, myocardial infarction, valvular heart disease, heart rhythm disorders and hypertension) with a view to recommendations regarding the value of prior cardiac evaluation. Results In the sample of backcountry skiers in the Gotthard area, only a small proportion of participants had risk factors. Especially smoking - the most important risk factor - was rare. The general amount of physical activity with an average of almost ten hours a week was high in the analysed sample. Nevertheless, seven young backcountry skiers suffered from hypertension, and there was one case of a valvular disease and one case of an arrhythmogenic disease. Conclusions Based on these results, with a prevalence of more than one percent, prior cardiac evaluation seems to be advisable for skiers with risk factors if altitudes change from intermediate levels (2000 to 3000 meters) to the High Alps, and generally when mountaineering is practiced in high altitude (Himalayas, Andes Mountains) due to the decrease in oxygen partial pressure.