Organochlorine Compounds in the Plasma of Peregrine Falcons and Gyrfalcons Nesting in Greenland

Levels of organochlorine compounds in the blood plasma of after-second-year female peregrine falcons (Falco peregrinus) were determined from samples collected from southern Greenland in 1985 and western Greenland from 1983 to 1989, and from adult and nestling gyrfalcons (Falco rusticolus) from western Greenland in 1989 and 1990. Samples were taken during nesting. Levels of p,p'-DDE(DDE) in peregrine plasma were 140 µg/kg wet weight geometric mean (GM) for the southern samples, and 220 µg/kg GM for the western samples. Calculated levels of DDE for eggs from plasma levels are below those associated with declining peregrine populations. Only DDE was found in the gyrfalcon plasma; levels were below 20 µg/kg. In addition to DDE, other organochlorines quantified in peregrine plasma included p,p'-DDD, p,p'-DDT, polychlorinated biphenyls, six chlordane compounds, ß-HCH, HCB, and Mirex. There was no trend over time for any of the compounds reported in peregrines except HCB, which decreased over the study period. There was no significant difference in the levels of the compounds reported between the regions. Females, which were sampled more than once, showed no clear trends with respect to increasing or decreasing residues.Key words: peregrine falcon, gyrfalcon, DDE, organochlorine, blood plasma, GreenlandOn a déterminé le niveau des composés organochlorés dans le plasma sanguin de faucons pèlerins (Falco peregrinus) femelles ayant plus de deux ans à partir d'échantillons provenant du Groenland méridional en 1985 et du Groenland occidental de 1983 à 1990, ainsi que de faucons gerfauts (Falco rusticolus) adultes et au nid prélevés dans le Groenland occidental en 1989 et 1990. Les échantillons ont été prélevés durant la période de nidification. Les niveaux de p,p'-DDE (DDE) dans le plasma des faucons pèlerins avaient une moyenne géométrique de 140 µg/kg de poids frais pour les échantillons provenant de la zone méridionale, et de 220 µg/kg pour les échantillons provenant de la zone occidentale. Les niveaux de DDE pour les oeufs, calculés à partir des niveaux de plasma, sont inférieurs à ceux que l'on associe avec les populations de faucons pèlerins en déclin. Seul le DDE a été trouvé dans le plasma du faucon gerfaut; les niveaux étaient inférieurs à 20 µg/kg. En plus du DDE, les autres organochlorés que l'on a quantifié dans le plasma du faucon pèlerin comprenaient le p,p'-DDD, p,p'-DDT, les polychlorés biphényls, six composés du chlordane, le ß-HCH, le HCB et le mirex. On n'a décelé de tendance pour aucun des composés trouvés dans les faucons pèlerins, sauf le HCB qui a diminué au cours de la période d'étude. On n'a noté aucune différence significative dans les niveaux des composés rapportés entre les diverses zones. Les femelles, qui ont fourni des échantillons plus d'une fois, n'ont pas montré de tendance nette en ce qui concerne une augmentation ou une diminution des résidus.Mots clés: faucon pèlerin, faucon gerfaut, DDE, organochloré, plasma sanguin, Groenlan

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

Major histocompatibility complex class I Chain-related A and B (MICA and MICB) gene, allele, and haplotype associations with dengue infections in ethnic thais

Background. Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. Methods. MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. Results. MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI,.21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI,.22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI,.14-.60). Conclusions. Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells

Enhancing the quality of extended life years. Identification of the oldest old with a very good and very poor quality of life

The objective of the study was to investigate quality of life in very old age by analyzing what proportion of older people had cumulative difficulties across several domains of quality of life, what proportion had no or few problems, and how these distributions changed over time. The design was a structured interview survey of people living in Hackney aged 85 and over at baseline, at two points in time. The follow-up interviews took place 2.5-3 years after the baseline interviews. The sample formed a census of all people aged 85 and over living in an East London borough, identified from centralized family doctors' records, validated against the electoral register. Respondents were interviewed at home by one of 12 trained interviewers. The subjects were 630 people aged 85 and over living at home, at baseline (70% response rate); 78% of survivors were re-interviewed. The main outcome measures were nine variables which were used to represent three major domains of quality of life: perceived 'wellbeing and autonomy','health and activity' (these two areas can be categorized under 'health and well being') and 'environment'. These were selected on the basis of the literature and information from focus groups held with study members, and measured using validated measurement scales and items. They were analyzed by respondents' sociodemographic characteristics, and features of their lives, and mortality up to 30 months after baseline. Close to half of older people achieved 'good' scores/on at least five of the nine indicators of quality of life used. Few people achieved 'good' scores on all nine items, or 'poor' scores on most items. The deterioration or increase in scores between the baseline and follow-up interviews among surviving sample members was not substantial. There was an association between number of 'good' quality of life scores and mortality within 30 months of baseline interview. The study confirms the great diversity of the elderly population, even in relatively homogeneous areas, and the need to adopt a multidimensional perspective on quality of life in old age. The study is unique in its longitudinal analysis of a very elderly population, and in adopting a multifaceted approach, rather than analyzing each domain of quality of life separately