Symptomatic prostatic cysts are not common. We report a case of a large complex cystic pelvic mass encountered in a Jordanian man that proved to be a huge midline prostatic cyst with seminal vesicle ...contained within the wall. This finding represents a variation of the newly proposed diagnosis, multilocular prostatic cystadenoma.
Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of the sterol ...12α-hydroxylase gene (Cyp8b1) results in complete absence of cholic acid (CA) and its derivatives. Here we investigate the effect of Cyp8b1 deletion on glucose homeostasis. Absence of Cyp8b1 results in improved glucose tolerance, insulin sensitivity, and β-cell function, mediated by absence of CA in Cyp8b1(-/-) mice. In addition, we show that reduced intestinal fat absorption in the absence of biliary CA leads to increased free fatty acids reaching the ileal L cells. This correlates with increased secretion of the incretin hormone GLP-1. GLP-1, in turn, increases the biosynthesis and secretion of insulin from β-cells, leading to the improved glucose tolerance observed in the Cyp8b1(-/-) mice. Thus, our data elucidate the importance of Cyp8b1 inhibition on the regulation of glucose metabolism.
Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively ...healthy older adults with hearing loss.
The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70–84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities ARIC study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422.
From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 24% from ARIC and 739 76% de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 88%). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (–0·200 95% CI –0·256 to –0·144 in the hearing intervention group and –0·202 –0·258 to –0·145 in the control group; difference 0·002 –0·077 to 0·081; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control.
The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline.
US National Institutes of Health.
Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing ...efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy.
•Methodology for fluorination of water collected during goethite dehydroxylation.•Significant intracrystalline temperature-dependent fractionation present in goethite.•Allows for the determination of ...goethite formation temperatures with uncertainties of 2-3°C.•Intracrystalline temperature dependence independent of bulk isotopic composition.
The crystal structure of goethite, FeO(OH), has two distinct oxygen sites, one with exclusively Fe-O bonds, the other with bonds to both iron and hydrogen. We developed a method to assess the oxygen isotope contrast between these sites by measuring both the bulk goethite and the oxygen released in the conversion of goethite to hematite. The method involves collecting the water released by dehydroxylation, fluorinating that population of extracted atoms, and measuring the resulting oxygen isotope composition (extracted δO18). Then, on a separate aliquot, all structural oxygen is fluorinated and measured (bulk δO18). Using synthetic goethite precipitates grown under controlled environmental conditions, we found significant temperature-dependent fractionation, εbulk-extracted=(5.51±0.26)×(106/T2)−(44.5±2.8); T in Kelvin). This intracrystalline fractionation forms the basis of a single-phase paleothermometer with an estimated uncertainty of ∼2-3°C. The temperature dependence appears to be independent of the isotopic composition of the parent fluid from which the goethite formed and the pH of that fluid. This intracrystalline thermometer can be used to simultaneously determine the formation temperature of a goethite and the isotopic composition of the water from which it formed. Natural goethites analyzed with this technique yield geologically reasonable formation temperatures of between 15 and 41°C.
BACKGROUNDCytochrome P450 family 8 subfamily B member 1 (CYP8B1) generates 12α-hydroxylated bile acids (BAs) that are associated with insulin resistance in humans.METHODSTo determine whether reduced ...CYP8B1 activity improves insulin sensitivity, we sequenced CYP8B1 in individuals without diabetes and identified carriers of complete loss-of-function (CLOF) mutations utilizing functional assays.RESULTSMutation carriers had lower plasma 12α-hydroxylated/non-12α-hydroxylated BA and cholic acid (CA)/chenodeoxycholic acid (CDCA) ratios compared with age-, sex-, and BMI-matched controls. During insulin clamps, hepatic glucose production was suppressed to a similar magnitude by insulin, but glucose infusion rates to maintain euglycemia were higher in mutation carriers, indicating increased peripheral insulin sensitivity. Consistently, a polymorphic CLOF CYP8B1 mutation associated with lower fasting insulin in the AMP-T2D-GENES study. Exposure of primary human muscle cells to mutation-carrier CA/CDCA ratios demonstrated increased FOXO1 activity, and upregulation of both insulin signaling and glucose uptake, which were mediated by increased CDCA. Inhibition of FOXO1 attenuated the CDCA-mediated increase in muscle insulin signaling and glucose uptake. We found that reduced CYP8B1 activity associates with increased insulin sensitivity in humans.CONCLUSIONOur findings suggest that increased circulatory CDCA due to reduced CYP8B1 activity increases skeletal muscle insulin sensitivity, contributing to increased whole-body insulin sensitization.FUNDINGBiomedical Research Council/National Medical Research Council of Singapore.
Random orientation of molecules within a sample leads to blurred observations of chemical reactions studied from the laboratory perspective. Methods developed for the dynamic imaging of molecular ...structures and processes struggle with this, as measurements are optimally made in the molecular frame. We used laser alignment to transiently fix carbon disulfide molecules in space long enough to elucidate, in the molecular reference frame, details of ultrafast electronic-vibrational dynamics during a photochemical reaction. These three-dimensional photoelectron imaging results, combined with ongoing efforts in molecular alignment and orientation, presage a wide range of insights obtainable from time-resolved studies in the molecular frame.
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