While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998-2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The proportion of homeless persons who were foreign-born increased from 24% in 1998-2002 to 39% in 2003-2007. Among foreign-born homeless persons with TB, 56% of infections were caused by strains not known to circulate among homeless persons in Toronto. Only 2% of infections were resistant to first-line TB medications. The rise in foreign-born homeless persons with TB strains likely acquired overseas suggests that the risk for drug-resistant strains entering the homeless shelter system may be escalating.
Cites: Am J Public Health. 2000 Mar;90(3):435-810705867
Cites: Ann Intern Med. 1992 Feb 15;116(4):299-3031733384
Cites: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):460-410934071
Cites: Int J Tuberc Lung Dis. 1999 Dec;3(12):1088-9510599012
Cites: Eur Respir J. 2000 Aug;16(2):209-1310968493
Cites: Ann Intern Med. 2000 Nov 21;133(10):779-8911085840
Cites: Int J Tuberc Lung Dis. 2002 Jul;6(7):615-2112102301
We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (ß = 3.8?mmol?l(-1), P = 2.5?×?10(-35)) and serum insulin (ß = 165?pmol?l(-1), P = 1.5?×?10(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (ß = -0.18 mmol?l(-1), P = 1.1?×?10(-6)) and fasting serum insulin (ß = -8.3?pmol?l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6?×?10(-24)). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (ß = 0.43?mmol?l(-1), P = 5.3?×?10(-5)). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.
Most common hereditary diseases in humans are complex and multifactorial. Large-scale genome-wide association studies based on SNP genotyping have only identified a small fraction of the heritable variation of these diseases. One explanation may be that many rare variants (a minor allele frequency, MAF
The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
Comment In: Cell Host Microbe. 2015 May 13;17(5):543-425974295
Erratum In: Cell Host Microbe. 2015 Jun 10;17(6):85226308884
Erratum In: Cell Host Microbe. 2015 Jun 10;17(6):852Jun, Wang [corrected to Wang, Jun]
Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.
Cites: Am J Hum Genet. 2009 Apr;84(4):477-8219303062
Institute of Polar Environment & Anhui Key Laboratory of Polar Environment and Global Change, Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei, 230026, China; College of Resources and Environment, Key Laboratory of Agricultural Environment in Universities of Shandong, Shandong Agricultural University, Tai'an, 271000, China.
Ny-Ålesund has been significantly impacted by anthropogenic activities (e.g. coal mining, scientific research, tourist shipping) over the past 100 years. However, the studies of potential toxic elements (PTEs) contamination in Ny-Ålesund currently mainly focus on surface soil or surface fjord sediments, and little is known about the history and status of PTEs contamination over the past 100 years. In this study, we collected a palaeo-notch sediment profile YN, analyzed the contents of six typical PTEs (Cu, Pb, Cd, Hg, As, Se) in the sediments, and assessed the historical pollution status in Ny-Ålesund using the pollution load index, geo-accumulation index and enrichment factor. The results showed that the contents of PTEs over the past 100 years increased rapidly compared with those during the interval of 9400-100 BP. In addition, Pb, Cd and Hg showed a clear signal of enrichment and were the main polluters among the PTEs analyzed. The contamination was likely linked to gas-oil powered generators, coal mining, research station, tourist shipping and long-range transport of pollutants.
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
Cites: Appl Environ Microbiol. 1999 Nov;65(11):4799-80710543789
Managing tuberculosis in foreign born patients entails a complex interaction between patient and provider.
Using a retrospective cohort study and survival analysis, this study evaluates the impact of patient and provider factors on the survival of foreign born outpatients with active tuberculosis. The primary outcome of the study is 1 year all-cause mortality.
In our cohort, patient-provider language discordance was associated with an increased risk of death [HR: 2.33; 95% CI: 1.39-3.88], while receiving treatment from a tuberculosis experienced physician [HR: 0.41; 95% CI: 0.22-0.77] and treatment in a dedicated tuberculosis clinic [HR: 0.53; 95% CI: 0.29-0.98] was associated with a lower risk of death.
Patient-provider communication and health systems factors played a large role in the survival of our cohort of foreign born tuberculosis outpatients. These findings suggest that language barriers and the provision of care by experienced providers in specialized clinic settings may have important effects on health outcomes.
The aim of this study was to examine how the major components of the metabolic syndrome relate to each other and to the development of diabetes using factor analysis.
The screening survey for type 2 diabetes was conducted in 1994, and a follow-up study of nondiabetic individuals at baseline was carried out in 1999 in the Beijing area. Among 934 nondiabetic and 305 diabetic subjects at baseline, factor analysis was performed using the principle components analysis with varimax orthogonal rotation of continuously distributed variables considered to represent the components of the metabolic syndrome. Fasting insulin was used as a marker for insulin resistance. Of the 559 subjects without diabetes at baseline, 129 developed diabetes during the 5-year follow-up. Factors identified at baseline were used as independent variables in univariate and multivariate logistic regression models to determine risk factor clusters predicting the development of diabetes.
Four factors were identified in nondiabetic and diabetic subjects. Fasting insulin levels, BMI, and waist-to-hip ratio were associated with one factor. Systolic and diastolic blood pressures were associated with the second factor. Two-hour postload plasma glucose (2-h PG) and serum insulin and fasting plasma glucose were associated with the third factor. Serum total cholesterol and triglycerides were associated with the fourth factor. The first and the third factors predicted the development of diabetes. In diabetic patients at baseline, the combination of systolic and diastolic blood pressure was the most important factor, and urinary albumin excretion rate clustered with fasting and 2-h PG levels.
Insulin resistance alone does not underlie all features of the metabolic syndrome. Different physiological processes associated with various components of the metabolic syndrome contain unique information about diabetes risk. Microalbunuria is more likely to be a complication of type 2 diabetes or hypertension than a marker for the metabolic syndrome.