A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru

Background: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls. / Methods: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network. / Results: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected. / Conclusions: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission

A retrospective study of PBDEs and PCBs in human milk from the Faroe Islands

BACKGROUND: Persistent organic pollutants (POPs) in wildlife and humans remain a cause of global concern, both in regard to traditional POPs, such as the polychlorinated biphenyls (PCBs), and emerging POPs, such as the polybrominated diphenyl ethers (PBDEs). To determine the time related concentrations, we analyzed human milk for these substances at three time points between 1987 and 1999. Polychlorobiphenylols (OH-PCBs), the dominating class of PCB metabolites, some of which are known to be strongly retained in human blood, were also included in the assessment. METHODS: We obtained milk from the Faroe Islands, where the population is exposed to POPs from their traditional diet (which may include pilot whale blubber). In addition to three pools, nine individual samples from the last time point were also analyzed. After cleanup, partitioning of neutral and acidic compounds, and separation of chemical classes, the analyses were carried out by gas chromatography and/or gas chromatography/mass spectrometry. RESULTS: Compared to other European populations, the human milk had high PCB concentrations, with pool concentrations of 2300 ng/g fat 1987, 1600 ng/g fat in 1994, and 1800 ng/g fat in 1999 (based on the sum of eleven major PCB congeners). The nine individual samples showed great variation in PCB concentrations. The OH-PCBs were present in trace amounts only, at levels of approximately 1% of the PCB concentrations. The PBDE concentrations showed a clear increase over time, and their concentrations in human milk from 1999 are among the highest reported so far from Europe, with results of individual samples ranging from 4.7 to 13 ng/g fat CONCLUSION: Although remote from pollution sources, the Faroe Islands show high concentrations of POPs in human milk, particularly PCBs, but also PBDEs. The PBDEs show increasing concentrations over time. The OH-PCB metabolites are poorly transferred to human milk, which likely is related to their acidic character

Environmental toxicity, redox signaling and lung inflammation:the role of glutathione

Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox sensitive transcription factors such as Nrf2, NF-κB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-L-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease

Stepwise Development of MAIT Cells in Mouse and Human

Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells

Exposure to p,p′-DDE: A Risk Factor for Type 2 Diabetes

BACKGROUND: Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study was performed within a well-defined cohort of women, age 50-59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p'-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p'-DDE). CONCLUSIONS/SIGNIFICANCE: The results from the present case-control study, including a follow-up design, confirms that p,p'-DDE exposure can be a risk factor for type 2 diabetes

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on Dietary reference values for water

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of dietary reference values for water for specific age groups. Adequate Intakes (AI) have been defined derived from a combination of observed intakes in population groups with desirable osmolarity values of urine and desirable water volumes per energy unit consumed. The reference values for total water intake include water from drinking water, beverages of all kind, and from food moisture and only apply to conditions of moderate environmental temperature and moderate physical activity levels (PAL 1.6). AIs for infants in the first half of the first year of life are estimated to be 100-190 mL/kg per day. For infants 6-12 months of age a total water intake of 800-1000 mL/day is considered adequate. For the second year of life an adequate total water intake of 1100-1200 mL/day is defined by interpolation, as intake data are not available. AIs of water for children are estimated to be 1300 mL/day for boys and girls 2-3 years of age; 1600 mL/day for boys and girls 4-8 years of age; 2100 mL/day for boys 9-13 years of age; 1900 mL/day for girls 9-13 years of age. Adolescents of 14 years and older are considered as adults with respect to adequate water intake. Available data for adults permit the definition of AIs as 2.0 L/day (P 95 3.1 L) for females and 2.5 L/day (P95 4.0 L) for males. The same AIs as for adults are defined for the elderly. For pregnant women the same water intake as in non-pregnant women plus an increase in proportion to the increase in energy intake (300 mL/day) is proposed. For lactating women adequate water intakes of about 700 mL/day above the AIs of non-lactating women of the same age are derive

InAs Quantum Dot Formation Studied at the Atomic Scale by Cross-sectional Scanning Tunnelling Microscopy

Self-assembled quantum dots (QDs) have attracted much attention in the last years. These nanostructures are very interesting from a scientifi c point of view because they form nearly ideal zero-dimensional systems in which quantum confi nement effects become very important. These unique properties also make them very interesting from a technological point of view. For example, InAs QDs are employed in QD lasers, single electron transistors, midinfrared detectors, single-photon sources, etc. InAs QDs are commonly created by the Stranski–Krastanov growth mode when InAs is deposited on a substrate with a bigger lattice constant, like GaAs or InP [10] . Above a certain critical thickness of InAs, three-dimensional islands are spontaneously formed on top of a wetting layer (WL) to reduce the strain energy. Once created, the QDs are subsequently capped, a step which is required for any device application. Self-assembled quantum dots (QDs) have attracted much attention in the last years. These nanostructures are very interesting from a scientifi c point of view because they form nearly ideal zero-dimensional systems in which quantum confi nement effects become very important. These unique properties also make them very interesting from a technological point of view. For example, InAs QDs are employed in QD lasers, single electron transistors, midinfrared detectors, single-photon sources, etc. InAs QDs are commonly created by the Stranski–Krastanov growth mode when InAs is deposited on a substrate with a bigger lattice constant, like GaAs or InP. Above a certain critical thickness of InAs, three-dimensional islands are spontaneously formed on top of a wetting layer (WL) to reduce the strain energy. Once created, the QDs are subsequently capped, a step which is required for any device application

Fish, Mercury, Selenium and Cardiovascular Risk: Current Evidence and Unanswered Questions

Controversy has arisen among the public and in the media regarding the health effects of fish intake in adults. Substantial evidence indicates that fish consumption reduces coronary heart disease mortality, the leading cause of death in developed and most developing nations. Conversely, concerns have grown regarding potential effects of exposure to mercury found in some fish. Seafood species are also rich in selenium, an essential trace element that may protect against both cardiovascular disease and toxic effects of mercury. Such protective effects would have direct implications for recommendations regarding optimal selenium intake and for assessing the potential impact of mercury exposure from fish intake in different populations. Because fish consumption appears to have important health benefits in adults, elucidating the relationships between fish intake, mercury and selenium exposure, and health risk is of considerable scientific and public health relevance. The evidence for health effects of fish consumption in adults is reviewed, focusing on the strength and consistency of evidence and relative magnitudes of effects of omega-3 fatty acids, mercury, and selenium. Given the preponderance of evidence, the focus is on cardiovascular effects, but other potential health effects, as well as potential effects of polychlorinated biphenyls and dioxins in fish, are also briefly reviewed. The relevant current unanswered questions and directions of further research are summarized

Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function