EEG signatures change during unilateral Yogi nasal breathing

Airflow through the left-and-right nostrils is said to be entrained by an endogenous nasal cycle paced by both poles of the hypothalamus. Yogic practices suggest, and scientific evidence demonstrates, that right-nostril breathing is involved with relatively higher sympathetic activity (arousal states), while left-nostril breathing is associated with a relatively more parasympathetic activity (stress alleviating state). The objective of this study was to further explore this laterality by controlling nasal airflow and observing patterns of cortical activity through encephalographic (EEG) recordings. Thirty subjects participated in this crossover study. The experimental session consisted of a resting phase (baseline), then a period of unilateral nostril breathing (UNB) using the dominant nasal airway, followed by UNB using the non-dominant nasal airway. A 64-channel EEG was recorded throughout the whole session. The effects of nostril-dominance, and nostril-lateralization were assessed using the power spectral density of the neural activity. The differences in power-spectra and source localization were calculated between EEG recorded during UNB and baseline for delta, theta, alpha, beta and gamma bands. Cluster-based permutation tests showed that compared to baseline, EEG spectral power was significantly (1) decreased in all frequency bands for non-dominant nostril UNB, (2) decreased in alpha, beta and gamma bands for dominant nostril UNB, (3) decreased in all bands for left nostril UNB, and (4) decreased in all bands except delta for right nostril UNB. The beta band showed the most widely distributed changes across the scalp. our source localisation results show that breathing with the dominant nostril breathing increases EEG power in the left inferior frontal (alpha band) and left parietal lobule (beta band), whereas non-dominant nostril breathing is related to more diffuse and bilateral effects in posterior areas of the brain.These preliminary findings may stimulate further research in the area, with potential applications to tailored treatment of brain disorders associated with disruption of sympathetic and parasympathetic activity

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Nasal microbial composition and chronic otitis media with effusion: A case-control study.

ObjectivesChronic otitis media with effusion (COME) in children can cause prolonged hearing loss, which is associated with an increased risk of learning delays and behavioural problems. Dispersal of bacterial pathogens from the nasal passages to the middle ear is implicated in COME. We sought to determine whether there is an association between nasal microbial composition and COME in children.MethodsA case-control study of children aged 3 and 4 years was conducted. Cases undergoing placement of tympanostomy tubes for COME were compared to healthy controls. Nasal swabs were collected and a questionnaire was administered. The V1-3 region of the 16S rRNA gene was amplified, and sequenced on the Illumina MiSeq.Results73 children with COME had a lower Shannon diversity index than 105 healthy controls (1.62 [.80] versus 1.88 [.84], respectively; P = .046). The nasal microbiota of cases and controls differed in composition using Bray-Curtis dissimilarity (p = 0.002). Children with COME had a higher abundance of otopathogens and lower abundance of commensals including alpha haemolytic Streptococci and Lactococcus. Cluster analysis revealed 4 distinct nasal microbial profiles. Profiles that were Corynebacterium-dominated (aOR 4.18 [95%CI, 1.68-10.39], Streptococcus-dominated (aOR 3.12 [95%CI, 1.08-9.06], or Moraxella-dominated (aOR 4.70 [95%CI, 1.73-12.80] were associated with COME, compared to a more mixed microbial profile when controlling for age, ethnicity, and recent antibiotics use.ConclusionsChildren with COME have a less diverse nasal microbial composition with a higher abundance of pathogens, compared to healthy children who have a more mixed bacterial profile with a higher abundance of commensals. Further research is required to determine how nasal microbiota may relate to the pathogenesis or maintenance of COME, and whether modification of the nasal microbiota can prevent or treat children at risk of COME

Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study.

Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. The aim of this study was to compare the effect of monthly high-dose vitamin D supplementation on a pain impact questionnaire (PIQ-6) score and prescription of analgesics in the general population. We performed a randomized, double-blind, placebo-controlled trial of 5108 community-dwelling participants, aged 50 to 84 years, who were randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. The PIQ-6 was administered at baseline, year 1, and final follow-up. Analgesic prescription data were collected from Ministry of Health. There was no difference in mean PIQ-6 score at the end of follow-up (adjusted mean difference: 0.06; P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants. The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%); the relative risk (RR) adjusted for age, sex, and ethnicity was 0.94 (P = 0.24). Similar results were observed for dispensing of nonsteroidal anti-inflammatory drugs (RR = 0.94; P = 0.24) and other nonopioids (RR = 0.98; P = 0.34). Focusing on vitamin D deficient participants (<50 nmol/L, 24.9%), there was a lower risk of dispensing nonsteroidal anti-inflammatory drugs in the vitamin D group compared with placebo (RR = 0.87; P = 0.009); all other subgroup analyses were not significant. Long-term monthly high-dose vitamin D supplementation did not improve mean PIQ-6 score or reduce analgesic dispensing in the general population