Characterization of the ion transport responses to ADH in the MDCK-C7 cell line

The Madin-Darby canine kidney (MDCK) cell line expresses many characteristics of the renal collecting duct. The MDCK-C7 subclone forms a high-resistance, hormone-responsive model of the principal cells, which are found in distal sections of the renal tubule. The electrophysiological technique of short-circuit current measurement was used to examine the response to antidiuretic hormone (ADH) in the MDCK-C7 clone. Three discrete electrogenic ion transport phenomena can be distinguished temporally and by the use of inhibitors and effectors. Initially the cells exhibit anion secretion through the cystic fibrosis transmembrane conductance regulator (CFTR). The presence of CFTR was confirmed by immunoprecipitation followed by Western blotting. The CFTR-mediated anion secretion is transient and is followed, in time, by a verapamil- and Ba(+)-sensitive anion secretion or cation absorption and, finally, by Na+ reabsorption via epithelial Na+ channels (ENaC). In contrast to other studies of MDCK cells, we see no indication that the presence of CFTR functionally inhibits ENaC. The characterization of the various ion transport phenomena substantiates this cell line as a model renal epithelium that can be used to study the hormonal and metabolic regulation of ion transport

Prevalence of Fibromyalgia: A Population‐Based Study in Olmsted County, Minnesota, Utilizing the Rochester Epidemiology Project

Objective To estimate and compare the prevalence of fibromyalgia by 2 different methods in Olmsted County, Minnesota. Methods The first method was a retrospective review of medical records of potential cases of fibromyalgia in Olmsted County using the Rochester Epidemiology Project (from January 1, 2005, to December 31, 2009) to estimate the prevalence of diagnosed fibromyalgia in clinical practice. The second method was a random survey of adults in Olmsted County using the fibromyalgia research survey criteria to estimate the percentage of responders who met the fibromyalgia research survey criteria. Results Of the 3,410 potential patients identified by the first method, 1,115 had a fibromyalgia diagnosis documented in the medical record by a health care provider. The age‐ and sex‐adjusted prevalence of diagnosed fibromyalgia by this method was 1.1%. By the second method, of the 2,994 people who received the survey by mail, 830 (27.6%) responded and 44 (5.3%) met the fibromyalgia research survey criteria. The age‐ and sex‐adjusted prevalence of fibromyalgia in the general population of Olmsted County by this method was estimated at 6.4%. Conclusion To the best of our knowledge, this is the first report of the rate at which fibromyalgia is being diagnosed in a community. This is also the first report of prevalence as assessed by the fibromyalgia research survey criteria. Our results suggest that patients, particularly men, who meet the fibromyalgia research survey criteria are unlikely to have been given a diagnosis of fibromyalgia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97488/1/21896_ftp.pd

Aortic valve replacement in patients aged 50 to 70 years: Improved outcome with mechanical versus biologic prostheses

ObjectiveImproved durability of bioprostheses has led some surgeons to recommend biologic rather than mechanical prostheses for patients younger than 65 years. We compared late results of contemporary bioprostheses and bileaflet mechanical prostheses in patients who underwent aortic valve replacement between 50 and 70 years old.MethodsIn this retrospective study, patients received either St Jude bileaflet valves or Carpentier–Edwards bioprostheses. Operations were performed between January 1991 and December 2000, and groups were matched one-to-one according to age, sex, need for coronary artery bypass grafting, and valve size.ResultsFour hundred forty patients were matched, and follow-up was 92% complete, with median durations of 9.1 years for patients who received mechanical valves and 6.2 years for patients who received bioprostheses. The 5- and 10-year unadjusted survivals were 87% and 68% for mechanical valves and 72% and 50% for bioprostheses, respectively (P < .01). Freedoms from reoperation at 10 years were 98% for mechanical valves and 91% for bioprostheses (P = .06). Rates of late stroke or other embolic events and of endocarditis were similar between groups. Hemorrhagic complications necessitating hospitalization occurred in 15% of patients with mechanical valves and 7% of patients with bioprostheses (P = .01). Notably, 19% of patients with bioprostheses were receiving warfarin sodium at last follow-up. After adjustment for unmatched variables, including diabetes, renal failure, lung disease, New York Heart Association functional class, ejection fraction, and stroke, the use of a mechanical valve was protective against late mortality (hazard ratio 0.46, P < .01).ConclusionIn this study, patients aged 50 to 70 years who underwent aortic valve replacement with mechanical valves had a survival advantage relative to matched patients who received bioprostheses. These findings question recommendations of bioprostheses for younger patients and suggest that a randomized trial may be warranted

Alterations in Platelet Function and Cell-Derived Microvesicles in Recently Menopausal Women: Relationship to Metabolic Syndrome and Atherogenic Risk

A woman’s risk for metabolic syndrome (MS) increases at menopause, with an associated increase in risk for cardiovascular disease. We hypothesized that early menopause-related changes in platelet activity and concentrations of microvesicles derived from activated blood and vascular cells provide a mechanistic link to the early atherothrombotic process. Thus, platelet functions and cellular origin of blood-borne microvesicles in recently menopausal women (n = 118) enrolled in the Kronos Early Estrogen Prevention Study were correlated with components of MS and noninvasive measures of cardiovascular disease [carotid artery intima medial thickness (CIMT), coronary artery calcium (CAC) score, and endothelial reactive hyperemic index (RHI)]. Specific to individual components of the MS pentad, platelet number increased with increasing waist circumference, and platelet secretion of ATP and expression of P-selectin decreased with increasing blood glucose (p = 0.005) and blood pressure (p < 0.05), respectively. Waist circumference and systolic blood pressure were independently associated with monocyte- and endothelium-derived microvesicles (p < 0.05). Platelet-derived and total procoagulant phosphatidylserine-positive microvesicles, and systolic blood pressure correlated with CIMT (p < 0.05), but not with CAC or RHI. In summary, among recently menopausal women, specific platelet functions and concentrations of circulating activated cell membrane-derived procoagulant microvesicles change with individual components of MS. These cellular changes may explain in part how menopause contributes to MS and, eventually, to cardiovascular disease

Phylogenomics and Morphological Reconstruction of Arcellinida Testate Amoebae Highlight Diversity of Microbial Eukaryotes in the Neoproterozoic

Life was microbial for the majority of Earth's history, but as very few microbial lineages leave a fossil record, the Precambrian evolution of life remains shrouded in mystery. Shelled (testate) amoebae stand out as an exception with rich documented diversity in the Neoproterozoic as vase-shaped microfossils (VSMs). While there is general consensus that most of these can be attributed to the Arcellinida lineage in Amoebozoa, it is still unclear whether they can be used as key fossils for interpretation of early eukaryotic evolution. Here, we present a well-resolved phylogenomic reconstruction based on 250 genes, obtained using single-cell transcriptomic techniques from a representative selection of 19 Arcellinid testate amoeba taxa. The robust phylogenetic framework enables deeper interpretations of evolution in this lineage and demanded an updated classification of the group. Additionally, we performed reconstruction of ancestral morphologies, yielding hypothetical ancestors remarkably similar to existing Neoproterozoic VSMs. We demonstrate that major lineages of testate amoebae were already diversified before the Sturtian glaciation (720 mya), supporting the hypothesis that massive eukaryotic diversification took place in the early Neoproterozoic and congruent with the interpretation that VSM are arcellinid testate amoebae

Ancient genomes show social and reproductive behavior of early Upper Palaeolithic foragers

Present-day hunter-gatherers (HGs) live in multilevel social groups essential to sustain a population structure characterized by limited levels of within-band relatedness and inbreeding. When these wider social networks evolved among HGs is unknown. Here, we investigate whether the contemporary HG strategy was already present in the Upper Paleolithic (UP), using complete genome sequences from Sunghir, a site dated to ~34 thousand years BP (kya) containing multiple anatomically modern human (AMH) individuals. Wedemonstrate that individuals at Sunghir derive from a population of small effective size, with limited kinship and levels of inbreeding similar to HG populations. Our findings suggest that UP social organization was similar to that of living HGs, with limited relatedness within residential groups embedded in a larger mating network

Echocardiographic findings and subsequent risk of native valve endocarditis

Background: The association of echocardiographic findings and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. The aim of this study was to determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and predisposing cardiac conditions were excluded. Only patients who had a TTE performed 6 months to 3 years before the development of LS-NVE were included as cases. Controls were patients within the same Mayo location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index, and echocardiography date. Results: There were 148 cases and 431 matched controls. As compared to controls, IE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) (p<0.001). Left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with LS-NVE. Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this pilot study. A larger cohort of LS-NVE patients, however, is needed to validate these findings

Sorption and Photodegradation Processes Govern Distribution and Fate of Sulfamethazine in Freshwater−Sediment Microcosms

The antibiotic sulfamethazine can be transported from manured fields to surface water bodies. We investigated the degradation and fate of sulfamethazine in pond water using 14C-phenyl-sulfamethazine in small pond water microcosms containing intact sediment and pond water. We found a 2.7-day half-life in pond water and 4.2-day half-life when sulfamethazine was added to the water (5 mg L–1 initial concentration) with swine manure diluted to simulate runoff. Sulfamethazine dissipated exponentially from the water column, with the majority of loss occurring via movement into the sediment phase. Extractable sulfamethazine in sediment accounted for 1.9–6.1% of the applied antibiotic within 14 days and then declined thereafter. Sulfamethazine was transformed mainly into nonextractable sediment-bound residue (40–60% of applied radioactivity) and smaller amounts of photoproducts. Biodegradation, as indicated by metabolite formation and 14CO2 evolution, was less significant than photodegradation. Two photoproducts accounted for 15–30% of radioactivity in the water column at the end of the 63-day study; the photoproducts were the major degradates in the aqueous and sediment phases. Other unidentified metabolites individually accounted for \u3c7% of radioactivity in the water or sediment. Less than 3% of applied radioactivity was mineralized to 14CO2. Manure input significantly increased sorption and binding of sulfamethazine residues to the sediment. These results show concurrent processes of photodegradation and sorption to sediment control aqueous concentrations and establish that sediment is a sink for sulfamethazine and sulfamethazine-related residues. Accumulation of the photoproducts and sulfamethazine in sediment may have important implications for benthic organisms