Metabolic Syndrome and its Correlates among Hypertensive Patients in Abuja, North Central Nigeria.

BACKGROUND: Metabolic syndrome is a constellation of abnormalities which includes central obesity, dyslipidaemia, elevated blood pressure and hyperglycemia. Hypertension, (which is a very common component of metabolic syndrome), and diabetes mellitus, are independently associated. Also, studies examining metabolic syndrome inAbuja, a city with affluence-driven lifestyle, are not available. This study aimed to investigate the prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria, as well as to examine the associations between metabolic syndrome and certain factors in that cohort of hypertensive patients. METHODS: This was a retrospective study that used data from hypertensive patients who attended clinic over a period of five years. Eight hundred and fifty-eight, (858-combined), case files of pre-treated, (previously known hypertensive patients) and newly diagnosed hypertensive participants were used for the study. The student t-tests were used to compare continuous variables, while Chi-square (χ2) tests were used for relationship between qualitative variables. The likelihood ratio test was employed to further confirm the statistical significance of certain independent variables relating with metabolic syndrome. A P-value of < 0.05 was considered statistically significant. RESULTS: The mean ages were 48.70±12.18, 49.19±11.06 and 48.2±13.3 years for combined group, the pre-treated and the newly-diagnosed groups respectively. The pre-treated, group consists of those previously known hypertensive patients, while the new group consists of those who were newly diagnosed hypertensive patients and were treatment naïve. The prevalence of metabolic syndrome in this study was 45.5% in the combined group, 47.23% in the pre-treated group and 37.3% in the newly diagnosed group. The commonest component of metabolic syndrome was reduced high density lipoprotein cholesterol, HDL-C. CONCLUSION: Metabolic syndrome is prevalent among hypertensive patients in Abuja, Nigeria. Some correlates of metabolic syndrome include; elevated BMI, truncal obesity, elevated total cholesterol, the use of thiazide diuretics and beta blockers as antihypertensives.

CONTEXTE: Le syndrome métabolique est une constellation d'anomalies qui comprend l'obésité centrale, la dyslipidémie, l'élévation de la pression artérielle et l'hyperglycémie. L'hypertension, qui est un composant très courant du syndrome métabolique, et le diabète sucré sont indépendamment associés. De plus, des études examinant le syndrome métabolique à Abuja, une ville au mode de vie axé sur l'aisance, ne sont pas disponibles. Cette étude visait à enquêter sur la prévalence du syndrome métabolique parmi les patients hypertendus à Abuja, au Nigeria, ainsi qu'à examiner les associations entre le syndrome métabolique et certains facteurs dans cette cohorte de patients hypertendus. MÉTHODES: Il s'agissait d'une étude rétrospective utilisant des données de patients hypertendus ayant fréquenté la clinique sur une période de cinq ans. Huit cent cinquante-huit (858 - combinés) dossiers de cas de patients hypertendus préalablement traités (patients hypertendus connus) et nouvellement diagnostiqués ont été utilisés pour l'étude. Les tests t de Student ont été utilisés pour comparer les variables continues, tandis que les tests du chi-carré (χ2) ont été utilisés pour examiner la relation entre les variables qualitatives. Le test du rapport de vraisemblance a été utilisé pour confirmer davantage la signification statistique de certaines variables indépendantes liées au syndrome métabolique. Une valeur P < 0,05 était considérée comme statistiquement significative. RÉSULTATS: Les âges moyens étaient de 48,70 ± 12,18, 49,19 ± 11,06 et 48,21 ± 13,3 ans pour le groupe combiné, le groupe prétraité et le groupe nouvellement diagnostiqué, respectivement. La prévalence du syndrome métabolique dans cette étude était de 45,5% dans le groupe combiné, 47,23% dans le groupe prétraité et 37,3% dans le groupe nouvellement diagnostiqué. Le composant le plus courant du syndrome métabolique était une diminution du cholestérol lipoprotéique de haute densité, le HDL-C. CONCLUSION: Le syndrome métabolique est prévalent parmi les patients hypertendus àAbuja, au Nigeria. Certains corrélats du syndrome métabolique comprennent un IMC élevé, une obésité tronculaire, une augmentation du cholestérol total, l'utilisation de diurétiques thiazidiques et de bêta-bloquants comme antihypertenseurs. Mots-clés: Syndrome métabolique, corrélats, patients hypertendus, Abuja Nigeria.

Precision Medicine Approach for Cardiometabolic Risk Factors in Therapeutic Apheresis.

Lipoprotein apheresis (LA) is currently the most powerful intervention possible to reach a maximal reduction of lipids in patients with familial hypercholesterolemia and lipoprotein(a) hyperlipidemia. Although LA is an invasive method, it has few side effects and the best results in preventing further major cardiovascular events. It has been suggested that the highly significant reduction of cardiovascular complications in patients with severe lipid disorders achieved by LA is mediated not only by the potent reduction of lipid levels but also by the removal of other proinflammatory and proatherogenic factors. Here we performed a comprehensive proteomic analysis of patients on LA treatment using intra-individually a set of differently sized apheresis filters with the INUSpheresis system. This study revealed that proteomic analysis correlates well with routine clinical chemistry in these patients. The method is eminently suited to discover new biomarkers and risk factors for cardiovascular disease in these patients. Different filters achieve reduction and removal of proatherogenic proteins in different quantities. This includes not only apolipoproteins, C-reactive protein, fibrinogen, and plasminogen but also proteins like complement factor B (CFAB), protein AMBP, afamin, and the low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) among others that have been described as atherosclerosis and metabolic vascular diseases promoting factors. We therefore conclude that future trials should be designed to develop an individualized therapy approach for patients on LA based on their metabolic and vascular risk profile. Furthermore, the power of such cascade filter treatment protocols may improve the prevention of cardiometabolic disease and its complications.

The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Lipoprotein(a): the underutilized risk factor for cardiovascular disease.

Raised lipoprotein(a) [Lp(a)] is an important independent cardiovascular risk factor and predictor of adverse outcomes. Challenges remain with regards to the screening, diagnosis and management of this condition. Although further prospective randomised controlled data is required, there is growing evidence suggesting that lowering Lp(a) may reduce the risk of cardiovascular events and ameliorate symptoms.

Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors.

Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Details about its synthesis, many aspects of composition and clearance from the bloodstream are still unknown. LDL receptor (LDLR) (and probably other receptors) play a role in the elimination of Lp(a) particles. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors increase the number of available LDLRs and in this way very effectively reduce the LDL cholesterol (LDL-C) concentrations. As shown in controlled studies using PCSK9 inhibitors, Lp(a) levels are decreased by 20 to 30%, though in some patients no effect was observed. So far, it has not been clarified whether this decrease is associated with an effect on the incidence of cardiovascular events (CVEs). In two recently published well-performed secondary prevention studies (FOURIER with evolocumab, ODYSSEY OUTCOMES with alirocumab) baseline Lp(a) levels were shown to have an impact on CVEs independently of baseline LDL-C concentrations. The rather modest PCSK9 inhibitor-induced decrease of Lp(a) was associated with a reduction of CVEs in both studies, even after adjusting (ODYSSEY OUTCOMES) for demographic variables (age, sex, race, region), baseline Lp(a), baseline LDL-C, change in LDL-C, and clinical variables (time from acute coronary syndrome, body mass index, diabetes, smoking history). The largest decrease of CVEs was seen in patients with relatively low concentrations of both LDL-C and Lp(a) (FOURIER). These findings will probably have an influence on the use of PCSK9 inhibitors in patients with high Lp(a) concentrations.

Lipoprotein(a)-an interdisciplinary challenge.

Lipoprotein(a) (Lp(a)) is an internationally recognized atherogenic risk factor which is inherited and not changed by nutrition or physical activity. At present, only proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may modestly decrease its concentration (but not in all patients)-leading to a certain decrease in cardiovascular events (CVE) in controlled studies. However, at present an elevation of Lp(a) is not a generally accepted indication for their use. More effective is lipoprotein apheresis (LA) therapy with respect to both lowering Lp(a) levels and reduction of CVE. In the future, an antisense oligonucleotide against apolipoprotein(a) will probably be available. Atherosclerosis in patients with an elevation of Lp(a) may affect several vessel regions (carotids, aorta, coronaries, leg arteries). Thus, Lp(a) should be measured in high-risk patients. These patients are usually cared for by their family doctors and by other specialists who should closely cooperate. Lipidologists should decide whether costly therapies like PCSK9 inhibitors or LA should be started. The main aim of current therapy is to optimize all other risk factors (LDL cholesterol, hypertension, diabetes mellitus, body weight, renal insufficiency). Patients should be regularly monitored (lab data, heart, arteries). This paper describes the duties of physicians of different specialties when caring for patients with high Lp(a) concentrations.

Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats.

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.

Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.

Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study.

BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12kcal/kg body weight of high protein and high fat for 11 months plus 30min of brisk walking daily and at least 3h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. RESULTS: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P<0.001 vs. medical arm), while ILM+liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P<0.001). More women allocated themselves to the ILM+liraglutide group. Weight loss was 43kg with SG, 26kg with ILM+liraglutide and 15kg with ILM alone. Lean body mass reductions were -11.6kg with SG, -6.3kg with ILM and -8.3kg with ILM+liraglutide. Prevalence of prediabetes was significantly lower with ILM+liraglutide, and insulin resistance was reduced by about 70% by both ILM+liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. DISCUSSION: At least in the short-term, liraglutide 3.0mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomised, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

Urinary Lipidomics: evidence for multiple sources and sexual dimorphism in healthy individuals.

Urinary lipidomics may add new valuable biomarkers to the diagnostic armamentarium for early detection of metabolic and kidney diseases. Sources and composition of urinary lipids in healthy individuals, however, have not been investigated in detail. Shotgun lipidomics was used to quantify lipidomic profiles in native urine samples from 16 individuals (eight men, eight women) collected in five fractions over 24 h. All probands were comprehensively characterized by urinary and clinical indices. The mean total urinary lipid concentration per sample was 0.84 µM in men and 1.03 µM in women. We observed significant intra- and interindividual variations of lipid concentrations over time, but failed to detect a clear circadian pattern. Based on quantity and subclass composition it seems very unlikely that plasma serves as major source for the urinary lipidome. Considering lipid metabolites occurring in at least 20% of all samples 38 lipid species from 7 lipid classes were identified. Four phosphatidylserine and one phosphatidylethanolamine ether species (PE-O 36:5) were detectable in almost all urine samples. Sexual dimorphism has been found mainly for phosphatidylcholines and phosphatidylethanolamines. In men and in women urinary lipid species were highly correlated with urinary creatinine and albumin excretion, reflecting glomerular filtration and tubular transport processes. In women, however, lipid species deriving from urinary cells and cellular constituents of the lower genitourinary tract considerably contributed to the urinary lipidome. In conclusion, our study revealed the potential of urinary lipidomics but also the complexity of methodological challenges which have to be overcome for its implementation as a routine diagnostic tool for renal, urological and metabolic diseases.

DHEA inhibits acute microglia-mediated inflammation through activation of the TrkA-Akt1/2-CREB-Jmjd3 pathway.

Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein. The latter induces the expression of the histone 3 lysine 27 (H3K27) demethylase Jumonji d3 (Jmjd3), which thereby controls the expression of inflammation-related genes and microglial polarization. Together, our data indicate that DHEA-activated TrkA signaling is a potent regulator of microglia-mediated inflammation in a Jmjd3-dependent manner, thereby providing the platform for potential future therapeutic interventions in neuro-inflammatory pathologies.

Lipoprotein apheresis influences monocyte subpopulations.

BACKGROUND: Monocytes can be differentiated into subpopulations depending on their expression profile of CD14 and CD16. CD16-positive monocytes are associated with coronary artery disease. Up to now, no data exist about the effect of lipoprotein apheresis (LA) on the distribution of monocyte subpopulations. METHODS: 80 patients who underwent LA at the University Hospital Dresden were included in the study. 8 out of the 80 LA patients received LA for the first time at the time point of blood analysis. Six different methods of LA were used (H.E.L.P. n = 8; Liposorber D n = 10; LF n = 14; DALI n = 17; MONET n = 11; Therasorb® LDL n = 12). Blood samples were taken immediately before and after LA and analyzed for CD14 and CD16 expression on monocytes. A total of 42 patients with cardiovascular risk factors but no indication for LA served as control group. RESULTS: The composition of monocyte-population was analyzed in regard to the 3 subpopulations. After LA, an increase in classical monocytes (CD14++CD16-) (93.3% vs. 93.9%, p < 0.01) and a decrease in non-classical monocytes (CD14+CD16+) (1.5% vs 1.0%; p < 0.001) were observed. LA did not change the amount of intermediate monocytes (CD14++CD16+) (5.3% vs. 5.1%). Two methods (MONET and Therasorb® LDL) did not influence the distribution of monocyte subpopulations. Interestingly, patients with LDL-C above 2.5 mmol/l prior LA showed increased amounts of intermediate monocytes. CONCLUSION: The distribution of monocyte populations is influenced by LA but depends on the distinct method of LA. Influences of LA were mainly observed in the content of classical and non-classical monocytes, whereas the intermediate monocyte population remained unaltered by LA.

Kinetics of Lipoprotein(a) in patients undergoing weekly lipoprotein apheresis for Lp(a) hyperlipoproteinemia.

INTRODUCTION: Lipoprotein apheresis (LA) represents the only effective therapeutic option for patients with elevated Lipoprotein(a) (Lp(a)) levels. We aimed at analyzing the Lp(a) reduction, rebound rates as well as mean interval values between two weekly apheresis sessions, since this might be important for the prediction of the residual cardiovascular risk and development of individualized approaches for this special therapeutic strategy. MATERIALS AND METHODS: 20 patients under weekly and 2 patients under twice weekly apheresis were included. We measured serum concentrations of Lp(a), total, LDL-, HDL - cholesterol and triglycerides daily over 7 days after single LA sessions. RESULTS: Mean Lp(a) levels was 158.1 ± 69.82 nmol/l before the LA session, decreased acutely by 76 ± 7% and increased to 97 ± 13% of the baseline value within 7 days in patients under weekly treatment. By mathematical modeling, the acute Lp(a) reduction can be calculated from the function: y (nmol/l) = 3.415 + 0.738 * x (R2 = 0.970), where x is the baseline Lp(a) value. The recovery rate can be predicted from the equation: y (%) = 22.49 + 18.64 * x - 1.14 * x2 (R2 = 0.874), where x is the day after apheresis. The empirical formula for the mean interval value is: y (nmol/l) = x - 12, where x is the absolute reduction in nmol/l. CONCLUSION: We modeled - for the first time - equations to predict the course of Lp(a) serum levels under weekly LA which are simple, reliable and enable the development of optimal individualized protocols of this costly lipid lowering therapy.

Dysregulation of the CD4+ T cells lineage differentiation in dyslipidemic patients and impact of lipoprotein-apheresis treatment: A case study.

BACKGROUND AND AIM: Lipoprotein-apheresis (LA) is a therapeutic approach used against severe forms of dyslipidemia in patients who are non-responders or intolerant to pharmacological treatments. However, little is known about the potential pleiotropic effects of LA, particularly regarding the immune system and its regulation. Thus, in an attempt to analyse the potential effects of dyslipidemia and LA on the regulation of CD4+ T cells activation and lineage differentiation, we compared the CD4+ T cells cytokines secretion profiles of dyslipidemic patients before and after LA with the profiles observed in healthy donors. METHODS: CD4+ T cells were isolated from 5 LA patients and 5 healthy donors and activated with anti-CD3 or anti-CD3 + anti-CD46 antibodies. The supernatants were collected after 36 h incubation and levels of secreted cytokines analysed by flow cytometry. RESULTS: Our results revealed a deep remodelling of CD4+ T cells cytokines secretion patterns in dyslipidemic patients compared to healthy donors, as reflected by a 15 times higher IFN-γ secretion rate after CD3 + CD46 co-activation in dyslipidemic patients after LA compared to healthy subjects and 8 times higher after CD3 activation alone (p = 0.0187 and p = 0.0118 respectively). Moreover, we demonstrated that LA itself also modifies the phenotype and activation pattern of CD4+ T-cells in dyslipidemic patients. CONCLUSION: These observations could be of fundamental importance in the improvement of LA columns/systems engineering and in developing new therapeutic approaches regarding dyslipidemia and associated pathologies such as atherosclerosis and type 2 diabetes.

Most significant reduction of cardiovascular events in patients undergoing lipoproteinapheresis due to raised Lp(a) levels - A multicenter observational study.

OBJECTIVES: Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study. METHODS: 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start. RESULTS: Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06). CONCLUSION: This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted.

Persistent LHPA Activation in German Individuals Raised in an Overprotective Parental Behavior.

Parental upbringing may affect their offspring's mental state across the entire lifespan. Overprotective parental child-rearing style may increase the disease burden in the offspring. Furthermore, this child-rearing style may also play a pathogenetic role by transmitting trauma- and stressor-related disorders (TSRD) across generations. Studies with animals have demonstrated that the mother's immediate and expansive protection of the newborn decreases the limbic-hypothalamic-pituitary-adrenal (LHPA) axis activity in the offspring. However, few studies have investigated how stress impact humans raised in an overprotective manner. In a cross-sectional study with 40 healthy students recalling their overprotective upbringing, we show an increase in the dehydroepiandrostendione (DHEA) concentration and a reduction in the cortisol/DHEA-ratio in hair. Additionally, this child rearing style was associated with heightened indications of mental burden, depressiveness, and sense of coherence. Our results provide insight into the roots and consequences of psychological trauma across several generations. Further investigations focusing particularly on multigenerational transmission in extremely burdened families will augment our results.

Circumcision does not alter long-term glucocorticoids accumulation or psychological effects associated with trauma- and stressor-related disorders.

Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease. This procedure has frequently been criticized by various communities claiming that circumcision in infancy and early adolescence were psychologically traumatizing with medical implications up into old age. Due to the lack of evidence concerning an alleged increase in vulnerability, we measured objective and subjective stress and trauma markers, including glucocorticoids from hair samples, in circumcised and non-circumcised males. We found no differences in long-term limbic-hypothalamic-pituitary-adrenal axis activity, subjective stress perception, anxiety, depressiveness, physical complaints, sense of coherence and resilience. Rather, an increase in the glucocorticoid levels indicated a healthy lifestyle and appropriate functioning. Thus, our findings provide evidence that male circumcision does not promote psychological trauma. Moreover, a qualitative approach, the ambivalence construct, was used for the discussion, aiming at a discourse devoid of biases.