Mitochondrial DNA depletion induces innate immune dysfunction rescued by interferon-γ

Monocytes from sepsis patients have mitochondrial DNA (mtDNA) depletion and immune deactivation. Here we find that THP-1 cell immune responses are impaired by experimentally depleting mtDNA, through dysregulated immune signalling, and rescued by interferon-γ treatment

Neuromuscular disease genetics in under-represented populations: increasing data diversity

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses \u27solved\u27 or \u27possibly solved\u27 ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% \u27solved\u27 and ∼13% \u27possibly solved\u27 outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

The “conscious pilot”—dendritic synchrony moves through the brain to mediate consciousness

Cognitive brain functions including sensory processing and control of behavior are understood as “neurocomputation” in axonal–dendritic synaptic networks of “integrate-and-fire” neurons. Cognitive neurocomputation with consciousness is accompanied by 30- to 90-Hz gamma synchrony electroencephalography (EEG), and non-conscious neurocomputation is not. Gamma synchrony EEG derives largely from neuronal groups linked by dendritic–dendritic gap junctions, forming transient syncytia (“dendritic webs”) in input/integration layers oriented sideways to axonal–dendritic neurocomputational flow. As gap junctions open and close, a gamma-synchronized dendritic web can rapidly change topology and move through the brain as a spatiotemporal envelope performing collective integration and volitional choices correlating with consciousness. The “conscious pilot” is a metaphorical description for a mobile gamma-synchronized dendritic web as vehicle for a conscious agent/pilot which experiences and assumes control of otherwise non-conscious auto-pilot neurocomputation

The risk of metabolic syndrome as a result of lifestyle among Ellisras rural young adults

The study aimed to investigate the association between metabolic syndrome (MetS) and lifestyle risk factors among Ellisras adults. A cross-sectional study was conducted on 624 adults (306 males and 318 females). MetS was defined according to the criteria of the International Diabetes Federation. The prevalence of MetS was 23.1% (8.6% males and 36.8 % females). Females appeared to have higher mean values for waist circumference (WC), fasting blood glucose (FBG), total cholesterol (TCHOL) and low-density lipoprotein cholesterol (LDL-C), while males had high mean values for high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). No significant age and gender differences were observed for dietary intake. Significantly more females (51.9%) presented with increased WC than males (4.6%). Participants who had a high dietary energy intake were significantly less likely to present with larger WC (OR: 0.250 95% CI [0.161; 0.389]), low HDL-C (OR: 0.306 95% CI [0.220; 0.425]) and high LDL-C (OR: 0.583 95% CI [0.418; 0.812]) but more likely to present with elevated FBG (OR: 1.01 95% CI [0.735; 1.386]), high TCHOL (OR: 1.039 95% CI [0.575; 1.337]), high TG (OR: 1.186 95% CI [0.695; 2.023]) and hypertension (OR: 5.205 95% CI [3.156; 8.585]). After adjusting for age, gender, smoking, and alcohol status, high energy intake was more than two times likely to predict MetS in adults with a large WC (OR: 2.766 95% CI [0.863; 3.477] and elevated FBG (OR: 2.227 95% CI [1.051; 3.328]). Therefore, identifying groups that are at an increased risk and those that are in their early stages of MetS will help improve and prevent the increase of the MetS in the future

Anti-inflammatory Components from Functional Foods for Obesity

Obesity, defined as excessive fat accumulation that may impair health, has been described throughout human history, but it has now reached epidemic proportions with the WHO estimating that 39% of the world’s adults over 18 years of age were overweight or obese in 2016. Obesity is a chronic low-grade inflammatory state leading to organ damage with an increased risk of common diseases including cardiovascular and metabolic disease, non-alcoholic fatty liver disease, osteo-arthritis and some cancers. This inflammatory state may be influenced by adipose tissue hypoxia and changes in the gut microbiota. There has been an increasing focus on functional foods and nutraceuticals as treatment options for obesity as drug treatments are limited in efficacy. This chapter summarises the importance of anthocyanin-containing fruits and vegetables, coffee and its components, tropical fruit and food waste as sources of phytochemicals for obesity treatment. We emphasise that preclinical studies can form the basis for clinical trials to determine the effectiveness of these treatments in humans