The clinical presentation of COVID-19 shows a remarkably broad spectrum of symptoms. Although studies with adult twins on SARS-CoV-2 infection are rare so far, the fact that there is a genetic ...component associated with the highly variable clinical outcomes of COVID-19 has already been highlighted in recent studies investigating potential candidate genes and polymorphisms. This is the first study of adult monozygotic (MZ) and dizygotic (DZ) twins concordantly affected by SARS-CoV-2 infection to estimate variances explained by genetic, shared, and individual environmental components of both somatic and psychological symptoms following SARS-CoV-2 infection.
Data were collected from 10 adult twin pairs (5 MZ, 5 DZ) in which both twins already had a SARS-CoV-2 infection. A self-designed questionnaire, the Barthel Index, and the Multidimensional Fatigue Inventory (MFI) were used to assess various symptoms and health status following SARS-CoV-2 infection. Intra-class correlations were calculated, and the Falconer formula was used to quantify and differentiate the percentages of genetic influences as well as common environment and personal experiences on the examined traits. In addition, potential factors influencing symptom burden were examined and discussed.
We found high estimated heritability for mental impairment after SARS-CoV-2 infection (
= 1.158) and for general fatigue (
= 1.258). For symptom burden, reduced activity, and reduced motivation the individual environment appears to have the strongest influence. Other fatigue symptoms are influenced by genetic effects which range between 42.8 and 69.4%.
Both genetics and individual environment play a role in health status after SARS-CoV-2 infection-mental status could be influenced primarily by genetic make-up, whereas for symptom burden and certain fatigue dimensions, non-shared environment could play a more critical role. Possible individual factors influencing the course of the disease were identified. However, gene-environment interactions may still be a source of differences between twins, and the search for candidate genes remains crucial on the road to personalized medicine.
Medizinische Zwillingsforschung in Deutschland Enck, Paul; Goebel-Stengel, Miriam; Rieß, Olaf ...
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
2021/10, Letnik:
64, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Zusammenfassung
Nach dem Zweiten Weltkrieg wurden weltweit Zwillingskohorten aufgebaut, die inzwischen ca. 1,5 Mio. Zwillinge umfassen und zwischen 1950 und 2012 über 2748 Zwillingsstudien ...hervorgebracht haben. Diese Zahl steigt jedes Jahr um weitere 500 bis 1000. Die Unterrepräsentanz deutscher Zwillingsstudien in diesen Datenbanken lässt sich nicht allein durch den Missbrauch medizinischer Forschung im Nationalsozialismus erklären. Entwicklung und Ausbau großer Zwillingskohorten sind ethisch und datenschutzrechtlich eine Herausforderung. Zwillingskohorten ermöglichen jedoch die Langzeit- und Echtzeiterforschung vieler medizinischer Fragestellungen; und die Zwillingsstudien tragen auch nach der Entschlüsselung des Humangenoms erheblich zur Beantwortung der Frage nach Anlage oder Umwelt als mögliche Erkrankungsauslöser bei.
Derzeit gibt es 2 deutsche Zwillingskohorten: die biomedizinische Kohorte
HealthTwiSt
mit ca. 1500 Zwillingspaaren und
TwinLife
, eine soziologisch-psychologische Kohorte mit ca. 4000 Zwillingspaaren. Daneben gibt es krankheitsspezifische Kohorten. 2016 startete das
TwinHealth
-Konsortium der Medizinischen Fakultät der Universität Tübingen mit dem Ziel, eine forschungsoffene und nachhaltige Zwillingsforschung am Standort Tübingen zur Bearbeitung unterschiedlicher Fragestellungen zu etablieren.
Der Artikel bietet mithilfe einer systematischen Literaturrecherche und einer medizinhistorischen Betrachtung einen Überblick über die weltweite und nationale Entwicklung von Zwillingsstudien und -datenbanken der letzten 100 Jahre. Anhand der Tübinger
TwinHealth
-Initiative beleuchtet er den Aufbau eines Zwillingskollektivs und dessen juristische, ethische und Datenschutzaspekte.
Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein ...expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects,
< 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (
< 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (
< 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (
< 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.
Tail pinch stimulates food intake in rats. We investigated brain mechanisms of this response and the influence of repeated exposure. Sprague-Dawley rats received acute (5 min) or repeated (5 min/day ...for 14 days) tail pinch using a padded clip. Acute tail pinch increased 5-min food intake compared with control (0.92 ± 0.2 vs. 0.03 ± 0.01 g,
P
< 0.01). This response was inhibited by 76% by intracerebroventricular injection of BIBP-3226, a neuropeptide Y
1
(NPY
1
) receptor antagonist, increased by 48% by astressin-B, a corticotropin-releasing factor (CRF) receptor antagonist, and not modified by S-406-028, a somatostatin subtype 2 antagonist. After the 5-min tail pinch without food, blood glucose rose by 21% (
P
< 0.01) while changes in plasma acyl ghrelin (+41%) and adrenocorticotropic hormone (+37%) were not significant. Two tail pinches (45 min apart) activate pontine and hindbrain catecholaminergic and hypothalamic paraventricular CRF neurons. After 14 days of repeated tail pinch, the 5-min orexigenic response was not significantly different from
days 2
to
11
but reduced by 50% thereafter (
P
< 0.001). Simultaneously, the 5-min fecal pellet output increased during the last 5 days compared with the first 5 days (+58%,
P
< 0.05). At
day 14
, the body weight gain was reduced by 22%, with a 99% inhibition of fat gain and a 25% reduction in lean mass (
P
< 0.05). The orexigenic response to acute 5-min tail pinch is likely to involve the activation of brain NPY
1
signaling, whereas that of CRF tends to dampen the acute response and may contribute to increased defecation and decreased body weight gain induced by repeated tail pinch.
(1) Background: Booster vaccinations for SARS-CoV-2 convalescents are essential for achieving herd immunity. For the first time, this study examined the influencing factors of vaccination willingness ...among SARS-CoV-2 infected individuals and identified vaccination-hesitant subgroups. (2) Methods: Individuals with positive SARS-CoV-2 PCR results were recruited by telephone. They completed an online questionnaire during their home isolation in Germany. This questionnaire assessed the vaccination willingness and its influencing factors. (3) Results: 224 home-isolated individuals with acute SARS-CoV-2 infection were included in the study. Vaccination willingness of home-isolated SARS-CoV-2 infected individuals with asymptomatic or moderate course was 54%. The following factors were associated with significantly lower vaccination willingness: younger age, foreign nationality, low income, low trust in vaccination effectiveness, fear of negative vaccination effects, low trust in the governmental pandemic management, low subjective informativeness about SARS-CoV-2, support of conspiracy theories. (4) Conclusions: The vaccination willingness of home-isolated SARS-CoV-2 infected individuals with asymptomatic or moderate symptomatic course was low. Motivational vaccination campaigns should be adapted to individuals with acute SARS-CoV-2 infection and consider the vaccination-hesitant groups. Vaccination education should be demand-driven, low-threshold, begin during the acute infection phase, and be guided for example by the established 5C model ("confidence, complacency, constraints, calculation, collective responsibility").
Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the ...possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5-25 kg/m(2)), underweight (anorexia nervosa, BMI < 17.5 kg/m(2)) and overweight (obesity with BMI 30-40, 40-50 and >50 kg/m(2), n = 14-15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m(2), n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m(2), n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9-85 kg/m(2), n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = -0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating.
During the pandemic, mental health was not only impaired in people after a SARS-CoV-2 infection, but also in people without previous infection. This is the first study on twins without prior ...SARS-CoV-2 infection to estimate the influence of genetic components and shared as well as individual environments on pandemic-associated fatigue. The study sample included 55 monozygotic and 45 dizygotic twin pairs. A total of 34.5% reported an increase in fatigue since the pandemic. A significant correlation was shown between the responses within monozygotic (χ21 = 11.14, p = 0.001) and dizygotic pairs (χ21 = 18.72, p < 0.001). In all pandemic-associated fatigue dimensions, individual environment (ranging from e2 = 0.64 to e2 = 0.84) and heritability (ranging from h2 = 0.32 to h2 = 1.04) seem to have the highest impact. The number of comorbidities significantly correlated with physical fatigue (Spearman’s ρ = 0.232, p < 0.001) and psychological impairment due to pandemic measures with the total fatigue score (Spearman’s ρ = 0.243, p < 0.001). However, calculated ANCOVAs with these significant correlations as covariates showed no significant influence on the mean values of the respective fatigue dimensions. Susceptibility to pandemic-associated fatigue may be genetically and environmentally determined, while intensity is also influenced by individual components. The prevalence of fatigue is high even in individuals without prior SARS-CoV-2 infection. Future mental health prevention and intervention programs should be implemented to alleviate the impact of the pandemic on the global population.
Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We ...investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity.
Due to phoenixin's role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide ...(LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (
= 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (
< 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold,
< 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (
< 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress.
Anorexia nervosa (AN) is accompanied by severe somatic and psychosocial complications. However, the underlying pathogenesis is poorly understood, treatment is challenging and often hampered by high ...relapse. Therefore, more basic research is needed to better understand the disease. Since hyperactivity often plays a role in AN, we characterized an animal model to mimic AN using restricted feeding and hyperactivity. Female Sprague-Dawley rats were divided into four groups: no activity/
feeding (
, AL,
= 9), activity/
feeding (activity, AC,
= 9), no activity/restricted feeding (RF,
= 12) and activity/restricted feeding (activity-based anorexia, ABA,
= 11). During the first week all rats were fed
, ABA and AC had access to a running wheel for 24 h/day. From week two ABA and RF only had access to food from 9:00 to 10:30 a.m. Body weight was assessed daily, activity and food intake monitored electronically, brain activation assessed using Fos immunohistochemistry at the end of the experiment. While during the first week no body weight differences were observed (
> 0.05), after food restriction RF rats showed a body weight decrease: -13% vs. day eight (
< 0.001) and vs. AC (-22%,
< 0.001) and AL (-26%,
< 0.001) that gained body weight (+10% and +13%, respectively;
< 0.001). ABA showed an additional body weight loss (-9%) compared to RF (
< 0.001) reaching a body weight loss of -22% during the 2-week restricted feeding period (
< 0.001). Food intake was greatly reduced in RF (-38%) and ABA (-41%) compared to AL (
< 0.001). Interestingly, no difference in 1.5-h food intake microstructure was observed between RF and ABA (
> 0.05). Similarly, the daily physical activity was not different between AC and ABA (
> 0.05). The investigation of Fos expression in the brain showed neuronal activation in several brain nuclei such as the supraoptic nucleus, arcuate nucleus, locus coeruleus and nucleus of the solitary tract of ABA compared to AL rats. In conclusion, ABA combining physical activity and restricted feeding likely represents a suited animal model for AN to study pathophysiological alterations and pharmacological treatment options. Nonetheless, cautious interpretation of the data is necessary since rats do not voluntarily reduce their body weight as observed in human AN.
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