The Swiss Spinal Cord Injury Cohort Study (SwiSCI) biobank: from concept to reality.

OBJECTIVES: To describe the concept, establishment and the operationalization of the biobank of the Swiss Spinal Cord Injury Cohort Study (SwiSCI), the available biosamples, and demographic and clinical characteristics of study participants. SETTING: The SwiSCI biobank is a platform for research within SwiSCI. It collects and processes serum, plasma, PBMCs, RNA, DNA, and urine from three rehabilitation centers. Samples are collected at admission to first rehabilitation and at discharge. Additionly, the biobank provides services to projects nested in SwiSCI or otherclinical trials among Spinal Cord Injury population. METHODS: Descriptive statistics were used for an overview of available biosamples, study participant characteristics, and comparison of the participating centers. RESULTS: Between the SwiSCI biobank establishment on June 27th, 2016, and October 19th, 2023, the SwiSCI Study has obtained informed consent from 524 individuals. Of these, 315 (60.1%) have agreed to donate biospecimens to the biobank. The average age of the contributors was 54 years (range: 38-65), with the majority being male (80%). Most participants suffered from traumatic injuries (66%) and were classified as paraplegic (64%). Approximately 80% presented with motor and sensory-incomplete SCI. The median Spinal Cord Independence Measure (SCIM) score was 31 (Interquartile Range: 19-58). The proportion of individuals providing paired biosamples at two distinct time points ranged from 63% (for RNA) to 65% (for urine and urine sediment). CONCLUSIONS: The SwiSCI biobank is a unique platform designed to serve as a basis for collaborative SCI research, including multi-omics approaches. The longitudinal collection of biospecimens and cryopreservation of multiple aliquots for each participant are fundamental for scrutinizing the temporal associations, ensuring research reproducibility, and achieving an adequate sample size for future investigations.

Systematic Review of the Effects of Oat Intake on Gastrointestinal Health.

BACKGROUND: Oats are a food source with multiple health benefits that could support beneficial bacterial groups and provide important bioactive compounds for the gut. OBJECTIVES: This review explores the association between oat intake, gastrointestinal (GI) symptoms, and microbial community changes in individuals with celiac disease (CeD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) and without GI disease. METHODS: Four databases and Google Scholar were systematically searched from inception until April 29, 2021. Clinical trials, observational studies, and in vitro studies with human gut-derived samples were included. RESULTS: There were 84 articles [23 randomized controlled trials (RCTs), 21 nonrandomized trials, 8 observational studies, and 32 in vitro studies] included. Oat intake increased total bacterial count, Lactobacilli spp., and Bifidobacterium spp. in healthy individuals and those with CeD. There was an increased concentration of short-chain fatty acids and improved gut permeability with oat intake but with no significant quality-of-life difference. In some individuals with CeD, consumption of certain oat types was associated with worsening of GI symptoms. We found no studies reporting on IBS and only 3 for IBD. The quality of RCTs showed some concerns mostly in domains of randomization (73.9%), whereas the quality of evidence of non-RCTs, observational studies, and in vitro studies was satisfactory. CONCLUSIONS: Oat intake was associated with the increase of beneficial bacterial groups in individuals without GI disease and those with CeD. Most studies showed no changes in GI symptoms with oat consumption. In vitro studies in CeD provide insight to oat-sensitive individuals and their GI mucosa, but the clinical studies remain limited, precluding our ability to draw firm conclusions. The prevalence of oat sensitivity in individuals with CeD should be further explored as this could improve clinical management and facilitate inclusion of oat in the diet for this population.

The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). METHODS: We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). RESULTS: We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, -14.5 mmHg, 95% CI -19.2, -9.9; -7.0 mmHg 95% CI -9.2, -4.8, respectively), lower triglycerides (-10.9 mg/dL, 95% CI -19.7, -2.1), total cholesterol (-9.9 mg/dL, 95% CI -14.5, -5.4), high-density lipoprotein (-1.7 mg/dL, 95% CI -3.3, -0.2) and low-density lipoprotein (-5.8 mg/dL, 95% CI -9.0, -2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (-10.3 mmHg, 95% CI -13.4, -7.1; -5.3 mmHg 95% CI -7.5, -3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. CONCLUSION: In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

Innovations in phenotyping of mouse models in the German Mouse Clinic.

Under the label of the German Mouse Clinic (GMC), a concept has been developed and implemented that allows the better understanding of human diseases on the pathophysiological and molecular level. This includes better understanding of the crosstalk between different organs, pleiotropy of genes, and the systemic impact of envirotypes and drugs. In the GMC, experts from various fields of mouse genetics and physiology, in close collaboration with clinicians, work side by side under one roof. The GMC is an open-access platform for the scientific community by providing phenotypic analysis in bilateral collaborations ("bottom-up projects") and as a partner and driver in international large-scale biology projects ("top-down projects"). Furthermore, technology development is a major topic in the GMC. Innovative techniques for primary and secondary screens are developed and implemented into the phenotyping pipelines (e.g., detection of volatile organic compounds, VOCs).

Body Composition According to Spinal Cord Injury Level: A Systematic Review and Meta-Analysis.

The level of injury is linked with biochemical alterations and limitations in physical activity among individuals with spinal cord injury (SCI), which are crucial determinants of body composition. We searched five electronic databases from inception until 22 July 2021. The pooled effect estimates were computed using random-effects models, and heterogeneity was calculated using I2 statistics and the chi-squared test. Study quality was assessed using the Newcastle-Ottawa Scale. We pooled 40 studies comprising 4872 individuals with SCI (3991 males, 825 females, and 56 sex-unknown) in addition to chronic SCI (median injury duration 12.3 y, IQR 8.03-14.8). Individuals with tetraplegia had a higher fat percentage (weighted mean difference (WMD) 1.9%, 95% CI 0.6, 3.1) and lower lean mass (WMD -3.0 kg, 95% CI -5.9, -0.2) compared to those with paraplegia. Those with tetraplegia also had higher indicators of central adiposity (WMD, visceral adipose tissue area 0.24 dm2 95% CI 0.05, 0.43 and volume 1.05 L 95% CI 0.14, 1.95), whereas body mass index was lower in individuals with tetraplegia than paraplegia (WMD -0.9 kg/mg2, 95% CI -1.4, -0.5). Sex, age, and injury characteristics were observed to be sources of heterogeneity. Thus, individuals with tetraplegia have higher fat composition compared to paraplegia. Anthropometric measures, such as body mass index, may be inaccurate in describing adiposity in SCI individuals.

Mice selected for high versus low stress reactivity: a new animal model for affective disorders.

Affective disorders such as major depression are among the most prevalent and costly diseases of the central nervous system, but the underlying mechanisms are still poorly understood. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions (hyper- or hypo-activity) of the hypothalamic-pituitary-adrenal (HPA) axis, play a prominent role in the development of major depressive disorders. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel parameters underlying increased or decreased stress reactivity. Starting from a population of outbred mice (parental generation: 100 males and 100 females of the CD-1 strain), two breeding lines were established according to the outcome of a 'stress reactivity test' (SRT), consisting of a 15-min restraint period and tail blood samplings immediately before and after exposure to the stressor. Mice showing a very high or a very low secretion of corticosterone in the SRT, i.e. animals expressing a hyper- or a hypo-reactivity of the HPA axis, were selected for the 'high reactivity' (HR) and the 'low reactivity' (LR) breeding line, respectively. Additionally, a third breeding line was established consisting of animals with an 'intermediate reactivity' (IR) in the SRT. Already in the first generation, i.e. animals derived from breeding pairs selected from the parental generation, significant differences in the reactivity of the HPA axis between HR, IR, and LR mice were observed. Moreover, these differences were found across all subsequent generations and could be increased by selective breeding, which indicates a genetic basis of the respective phenotype. Repeated testing of individuals in the SRT furthermore proved that the observed differences in stress responsiveness are present already early in life and can be regarded as a robust genetic predisposition. Tests investigating the animal's emotionality including anxiety-related behavior, exploratory drive, locomotor activity, and depression-like behavior point to phenotypic similarities with behavioral changes observed in depressive patients. In general, HR males and females were 'hyperactive' in some behavioral paradigms, resembling symptoms of restlessness and agitation often seen in melancholic depression. LR mice, on the other hand, showed more passive-aggressive coping styles, corresponding to signs of retardation and retreat observed in atypical depression. Several morphometric and neuroendocrine findings further support this view. For example, monitoring the circadian rhythm of glucocorticoid secretion revealed clearly increased trough levels in HR mice, resulting in a flattened diurnal rhythm, again adding to the neuroendocrine similarities to patients suffering from melancholic depression. Taken together, our results suggest that distinct mechanisms influencing the function and regulation of the HPA axis are involved in the respective behavioral and neurobiological endophenotypes. Thus, the generated HR/IR/LR mouse lines can be a valuable model to elucidate molecular genetic, neuroendocrine, and behavioral parameters associated with altered stress reactivity, thereby improving our understanding of affective disorders, presumably including the symptomatology and pathophysiology of specific subtypes of major depression.

MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy.

Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.