1,517 research outputs found

    Perched Ponds: An Arctic Variety

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    Data obtained during several seasons of field research on a small drainage basin in the Colville River delta of northern Alaska were used in a study of permafrost as an aquaclude for the maintenance of a pond above the regional water table. The development of the active layer of permafrost in the basin and the water budget of the pond were monitored. It was shown that the permafrost table enables the general form of the basin's subaerial surface to be maintained throughout the thaw season. The resulting prevention of percolation, when combined with a low evaporation rate, is sufficient to ensure that the pond is perennial

    HIF-mediated innate immune responses: cell signaling and therapeutic implications

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    Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs) are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out

    Genetic diversity and evidence for acquired antimicrobial resistance in Mycobacterium tuberculosis at a large hospital in South India

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    AbstractObjectives: To assess genetic diversity and drug resistance of Mycobacterium tuberculosis isolates collected at Christian Medical College Hospital (CMCH), Vellore, India, between July 1995 and May 1996.Materials and Methods: Isolates were subjected to IS6110-based restriction fragment length polymorphism (RFLP) analysis and tested for resistance to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide, and DNA from selected strains was sequenced in regions associated with drug resistance.Results: One hundred and one M. tuberculosis isolates were collected from 87 patients with pulmonary tuberculosis. Charts of 69 patients were reviewed for history of tuberculosis illness and treatment. DNA from 29 strains was sequenced in katG, rpoB, and gyrA, and sometimes pncA regions. Analysis by RFLP revealed a high degree of genetic diversity, with no identifiable clusters of infection. Of the strains tested, 51 % were resistant to at least one antibiotic, and 43% were resistant to more than one drug. There was a high rate of resistance observed in patients whose charts indicated a history of improperly administered tuberculosis treatment, whereas little drug resistance was observed in patients never previously treated for tuberculosis. Sequencing of genes associated with drug resistance revealed several previously unreported mutations in resistant strains.Conclusions: This analysis suggests that the cases of tuberculosis in the sample are largely reactivation of long-standing infections and that the drug resistance among patients in CMCH is largely acquired or secondary rather than attributable to the spread of drug-resistant strains

    Biallelic inheritance of hypomorphic PKD1 variants is highly prevalent in very early onset polycystic kidney disease

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    Purpose To investigate the prevalence of biallelic PKD1 and PKD2 variants underlying very early onset (VEO) polycystic kidney disease (PKD) in a large international pediatric cohort referred for clinical indications over a 10-year period (2010–2020). Methods All samples were tested by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) of PKD1 and PKD2 genes and/or a next-generation sequencing panel of 15 additional cystic genes including PKHD1 and HNF1B. Two patients underwent exome or genome sequencing. Results Likely causative PKD1 or PKD2 variants were detected in 30 infants with PKD-VEO, 16 of whom presented in utero. Twenty-one of 30 (70%) had two variants with biallelic in trans inheritance confirmed in 16/21, 1 infant had biallelic PKD2 variants, and 2 infants had digenic PKD1/PKD2 variants. There was no known family history of ADPKD in 13 families (43%) and a de novo pathogenic variant was confirmed in 6 families (23%). Conclusion We report a high prevalence of hypomorphic PKD1 variants and likely biallelic disease in infants presenting with PKD-VEO with major implications for reproductive counseling. The diagnostic interpretation and reporting of these variants however remains challenging using current American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) and Association of Clinical Genetic Science (ACGS) variant classification guidelines in PKD-VEO and other diseases affected by similar variants with incomplete penetrance

    Health care professionals’ attitudes towards evidence-based medicine in the workers’ compensation setting: a cohort study

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    Abstract Background Problems may arise during the approval process of treatment after a compensable work injury, which include excess paperwork, delays in approving services, disputes, and allegations of over-servicing. This is perceived as undesirable for injured people, health care professionals and claims managers, and costly to the health care system, compensation system, workplaces and society. Introducing an Evidence Based Medicine (EBM) decision tool in the workers’ compensation system could provide a partial solution, by reducing uncertainty about effective treatment. The aim of this study was to investigate attitudes of health care professionals (HCP) to the potential implementation of an EBM tool in the workers’ compensation setting. Methods The study has a mixed methods design. The quantitative study consisted of an online questionnaire asking about self-reported knowledge, attitudes and behaviour to EBM in general. The qualitative study consisted of interviews about an EBM tool being applied in the workers’ compensation process. Participants were health care practitioners from different clinical specialties. They were recruited through the investigators’ clinical networks and the workers’ compensation government regulator’s website. Results Participants completing the questionnaire (n = 231) indicated they were knowledgeable about the evidence-base in their field, but perceived some difficulties when applying EBM. General practitioners reported having the greatest obstacles to applying EBM. Participants who were interviewed (n = 15) perceived that an EBM tool in the workers’ compensation setting could potentially have some advantages, such as reducing inappropriate treatment, or over-servicing, and providing guidance for clinicians. However, participants expressed substantial concerns that the EBM tool would not adequately reflect the impact of psychosocial factors on recovery. They also highlighted a lack of timeliness in decision making and proper assessment, particularly in pain management. Conclusions Overall, HCP are supportive of EBM, but have strong concerns about implementation of EBM based decision making in the workers’ compensation setting. The participants felt that an EBM tool should not be applied rigidly and should take into account clinical judgement and patient variability and preferences. In general, the treatment approval process in the workers’ compensation insurance system is a sensitive area, in which the interaction between HCP and claims managers can be improved

    Association of the resolvin precursor 17-HDHA, but not D- or E- series resolvins, with heat pain sensitivity and osteoarthritis pain in humans

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    Resolvins are omega-3 fatty acid derived potent bioactive lipids that resolve inflammation and modulate transient receptor potential channels. Exogenous administration of the resolvin precursor 17-HDHA shows a strong analgesic effect in animal models of osteoarthritis and acute inflammatory pain, but has not been studied in humans. Our aim was to assess the role of 17-HDHA and resolvins in heat pain sensitivity and in osteoarthritis pain in humans. Resolvins D1, D2, D3, D5, E1 and 17-HDHA, were measured by liquid chromatography-mass spectrometry and tested for association with heat pain thresholds in 250 healthy volunteers who had undergone quantitative sensory testing. Resolvins D1, D2 and 17-HDHA were then tested in 62 individuals affected with knee osteoarthritis and 52 age matched controls and tested for association with knee pain. Circulating levels of docosahexaenoic acid (DHA) were also measured. Levels of 17-HDHA, but not those of the other 5 resolvins tested, were associated with increased heat pain thresholds (beta = 0.075; 95%CI 0.024, 0.126; p<0.0046). 17-DHDA was associated with lower pain scores in OA patients (beta -0.41; 95%CI-0.69, -0.12; p<0.005; adjusted for covariates) but not with osteoarthritis. The associations of 17-HDHA associations with heat pain sensitivity and osteoarthritis pain were independent of DHA levels
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