Vasopressin-independent renal urinary concentration: Increased rBSC1 and enhanced countercurrent multiplication

Vasopressin-independent renal urinary concentration: Increased rBSC1 and enhanced countercurrent multiplication.BackgroundA close association between the expression of the sodium transporter, rat bumetanide sensitive cotransporter (rBSC), in thick ascending limb of Henle and urinary concentration has been reported. However, direct evidence for this association and the mechanism of rBSC1 expression are still to be elucidated.MethodsBrattleboro (BB) rats weighing approximately 200g were dehydrated by water restriction for 4 hours, which induced around a 5% body weight reduction. Although plasma arginine vasopressin (AVP) was undetectable even after the water restriction, BB rats concentrated urine from 182 ± 23 (mean ± SD) at baseline to 404 ± 65 mOsm/kg · H2O.ResultsUrinary volume was reduced from 5.8 ± 1.8 to 1.4 ± 0.6mL/h. This treatment significantly increased sodium and urea accumulation in the renal medulla and reduced urinary sodium excretion. rBSC1 signals for both mRNA and protein were increased in dehydrated rats, although aquaporin type 2 (AQP2) expression was not enhanced in dehydrated BB rats. Subcutaneous infusion of desmopressin acetate (DDAVP) intensified rBSC1 signals of BB rats more than those in dehydrated condition.ConclusionDehydration increased rBSC1 expression and enhanced countercurrent multiplication even in AVP deficiency. These results supply strong evidence for the association between rBSC1 expression and urinary concentration, and indicate the presence of an AVP-independent mechanism for urine concentration

The effectiveness of Modified Early Warning Score (MEWS) using individual-specific range in predicting pneumonia hospitalization among nursing home residents in Japan: Comparison with National Early Waring Score (NEWS)

Aim: The purpose of this study was to compare the usefulness between the National Early Warning Score (NEWS), which uses the absolute value range, and the Modified Early Warning Score (MEWS), which considers individual-specific ranges (evaluated by mean and standard deviation [SD], relative measures), in predicting pneumonia hospitalization among nursing home residents.Methods: The current study was a retrospective, observational study. The subjects were 235 nursing home residents (75 men and 160 women; pneumonia group, n=62; non-pneumonia group, n=173). The mean and SD of each vital sign (systolic blood pressure, heart rate, body temperature, and oxygen saturation) of each subject recorded over 28 days was calculated. In the pneumonia group, the points at the date of hospitalization were aggregated to derive the NEWS and MEWS. In the non-pneumonia group, the point at the 35th day from the start of the nursing home stay was aggregated to derive the NEWS and MEWS.Results: The area under the curve (AUC) for predicting pneumonia hospitalization was 0.80 (95% confidence interval [CI], 0.72- 0.88) for NEWS and 0.92 (95%CI, 0.87-0.97) for MEWS using individual-specific ranges. The AUC of MEWS using individualspecific ranges was significantly greater than that of NEWS (p<0.0001). When 3 was used as a cutoff value in MEWS, the Youden Index was the best value (0.75). Sensitivity, pecificity, positive predictive value, and negative predictive value were 0.77, 0.97, 0.91, and 0.92, respectively.Conclusion: Our MEWS system using individual-specific ranges showed good performance in predicting hospitalization for pneumonia among nursing home residents

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy

Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy.BackgroundRenal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated.MethodsLi nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined.ResultsRats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 ± 11 (mean ± SD) at baseline to 450 ± 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved.ConclusionsOur results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function

Association of Physical Performance and Pain With Fear of Falling Among Community?Dwelling Japanese Women Aged 65 Years and Older

Our aim was to explore the association of physical performance and pain with fear of falling among community-dwelling Japanese women. The subjects were 278 women aged 65 years and over. We collected information on fear of falling, painful joints, comorbidities, falls in the previous year, and cataracts. Walking time (distance of 6 m), chair stand time (5 times), grip strength, the timed up and go test (TUG), and functional reach were measured. The prevalence of fear of falling was 36.3%, and it increased with age, but it was not significant (P=0.081). Multivariate logistic regression analysis showed that poor physical performance (longer walking time, longer chair stand time, weaker grip strength, and longer TUG) and pain (low back, and upper and lower extremity pain) were significantly associated with fear of falling after adjusting for age, body mass index, comorbidities, falls in the previous year, and cataracts. Maintaining physical functioning and managing pain may be important for elderly women with fear of falling

Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women

BACKGROUND: An increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women. METHODS: The subjects were community-dwelling men (n = 358) and women (n = 503) aged ? 40?years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected. RESULTS: Serum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ? 80?years than those in the age groups of 40-49, 50-59, and 60-69?years. Serum ucOC concentrations in women were higher in the age groups of 50-59 and 60-69?years than those at 40-49?years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men. CONCLUSIONS: Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women

Association between mental health and bone mass among community-dwelling adults: Nagasaki Islands Study on bone health

Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders(age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures

Association of FTO genotype with obesity and bone health among communitydwelling adults ; Goto Island study on bone health

Bone mass is tuned by various factors, including aging, menopause, low body weight, and genetic variations. Here, we showed an independent association between a genotype on the fat mass- and obesity-associated FTO gene (#610966 on OMIM) and bone loss after adjusting for age and body mass index (BMI). A cross-sectional study was nested in a prospective observational study of 1,828 participants (median age: 69 [62-76] years in men and 68 [61-75] years in women) residing in a rural city in western Japan (Goto Island study). Participants were recruited during medical checkups in 2014 and 2016 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. The single nucleotide polymorphism (SNP) rs1421085 was genotyped using a hydrolysis probe. The chi-squared test was used to determine whether the variants were in equilibrium in this population. There were differences in medians of BMI among the genotypes (24.3 in CC, 23.0 in CT, and 22.6 in TT, P = 0.01), but not in those of bone mass. There was a significant association between the minor allele (C) and being overweight in a gene dosage-dependent manner (BMI > 25, OR per allele =1.52, 95% CI = 1.07-2.14, P = 0.02 in men, OR = 1.48, 95% CI = 1.16-1.95, P = 0.01 in women). Logistic regression analysis showed a significant protective association in male carriers of the minor allele against low bone mass (QUS T-score less than -2.0) after adjusting for age and BMI in men aged 65-75 years (OR = 0.50, 95% CI = 0.27-0.96, P = 0.036), with no significant association in women.Our study indicated an association between the genetic polymorphism of FTO and bone mass among community-dwelling men aged 65-75 years. The polymorphism may play a role in bone health with higher BMI and other beneficial functions

Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study: Setting and Participants; The survey population included 1008 postmenopausal women 50?92 years of age residing in rural communities. Methods: Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p < 0.001). Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women

Effect of self-reported walking difficulty on bone mass and bone resorption marker in Japanese people aged 40?years and over

Background: This study aimed to examine the association of walking difficulty with bone mass or bone turnover among community-dwelling Japanese people aged 40 years and older. Methods: We studied 1097 community-dwelling Japanese people aged 40 years and older (379 men and 718 women) who were invited to participate in periodic health examinations in 2006?2009. Walking difficulty was defined as having difficulty walking 100 m on a level surface (self-administered questionnaire). Calcaneal stiffness index (bone mass) was measured by quantitative ultrasound. Spot urine samples were collected, and urinary N-terminal cross-linking telopeptide of type I collagen (NTx) was measured. Values were corrected for creatinine (Cre) concentration. Results: The prevalence of walking difficulty was significantly higher in women than in men (7.4 vs. 3.4 %, p?=?0.011) and significantly increased with age in men (p for trend?=?0.02) and women (p for trend <0.001). In univariate analysis, men and women with walking difficulty were older (p?<?0.001) and had a lower stiffness index (p?<?0.001), compared with those without walking difficulty. Among women, individuals with walking difficulty had significantly higher urinary NTx/Cre than those without walking difficulty (p?<?0.001); however, this was not so among men (p?=?0.39). Multiple regression analysis adjusted for age, weight, and menopausal status showed a significant association between walking difficulty and lower stiffness index in men (p?=?0.004) and women (p?=?0.005). In women, walking difficulty was significantly associated with higher NTx/Cre (p?=?0.001), but not in men (p?=?0.35). Conclusions: Walking difficulty may contribute to low bone mass in both sexes but might cause high bone turnover in women only

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements