An analysis of factors contributing to household transmission of COVID-19-using data from active epidemiological investigations performed in the Setagaya ward of Tokyo, Japan.

An active epidemiological investigation of COVID-19 cases in the Setagaya ward of Tokyo revealed that household transmission was the main route of infection spread. This study aimed to identify the factors affecting household transmission in patients diagnosed with COVID-19 and their cohabitants, during the wild type virus (December 2020) and alpha variant epidemic (May 2021). Index case factors significantly associated with household transmission for both wild type (WT) and alpha variant (AV), were at least 3 days from onset to diagnosis (WT: risk ratio [RR] 1.44, 95% confidence interval [CI] 1.16-1.79/AV: RR 1.66, CI 1.32-2.08), and a household size of three or more people (WT: RR 1.37, CI 1.10-1.72/AV: RR 1.29, CI 1.05-1.59). There were also significant differences in age ≥ 65 (RR 2.39, CI 1.26-4.54) and symptomatic at diagnosis (RR 3.05, CI 1.22-7.63) in index cases of WT. Among cohabitants, factors associated with household transmission for both strains were being the spouse/partner of the index case (WT: RR 1.68, CI 1.21-1.82/AV: RR 1.97, CI 1.59-2.43) and at least 3 days from onset to diagnosis of the index case (WT: RR 1.48, CI 1.34-2.10/ AV: RR 1.86, CI1.52-2.28). Early diagnosis and isolation are effective for preventing household transmission.

Combinatorial characterization of metastable luminous silver cations.

Thermodynamically metastable glasses that can contain metastable species are important functional materials. X-ray absorption near-edge structure (XANES) spectroscopy is an effective technique for determining the valence states of cations, especially for the doping element in phosphors. Herein, we first confirm the valence change of silver cations from monovalent to trivalent in aluminophosphate glasses by X-ray irradiation using a combination of Ag L3-edge XANES, electron spin resonance, and simulated XANES spectra based on first-principles calculations. The absorption edge of the experimental and simulated XANES spectra demonstrate the spectral features of Ag(III), confirming that AgO exists as Ag(I)Ag(III)O2. A part of Ag(I) changes to Ag(III) by X-ray irradiation, and the generation of Ag(III) is saturated after high irradiation doses, in good agreement with conventional radiophotoluminescence (RPL) behaviour. The structural modelling based on a combination of quantum beam analysis suggests that the local coordination of Ag cations is similar to that of Ag(III), which is confirmed by density functional theory calculations. This demonstration of Ag(III) in glass overturns the conventional understanding of the RPL mechanism of silver cations, redefining the science of silver-related materials.

Sodium glucose cotransporter 2 inhibitor suppresses renal injury in rats with renal congestion.

Renal congestion is an issue of cardiorenal syndrome in patients with heart failure. Recent clinical and basic studies suggest a renoprotective potential of sodium-glucose cotransporter (SGLT) 2 inhibitors. However, the effect on renal congestion and its mechanism is not fully understood. Thus, we aimed to clarify the effect of SGLT inhibition in a renal congestion model. Renal congestion was induced in the left kidney of male Sprague-Dawley rats by ligation of the inferior vena cava between the renal veins. The SGLT2 inhibitor tofogliflozin or vehicle was orally administered daily from the day before IVC ligation until two days after surgery. On the third postoperative day, both the right control kidney and the left congested kidney were harvested and analyzed. Kidney weight and water content was increased, and renal injury and fibrosis were observed in the left congested kidney. Kidney weight gain and hydration were improved with tofogliflozin treatment. Additionally, this treatment effectively reduced renal injury and fibrosis, particularly in the renal cortex. SGLT2 expression was observed in the congested kidney, but suppressed in the damaged tubular cells. Molecules associated with inflammation were increased in the congested kidney and reversed by tofogliflozin treatment. Mitochondrial dysfunction provoked by renal congestion was also improved by tofogliflozin treatment. Tofogliflozin protects against renal damage induced by renal congestion. SGLT2 inhibitors could be a candidate strategy for renal impairment associated with heart failure.

Pericyte detachment and renal congestion involve interstitial injury and fibrosis in Dahl salt-sensitive rats and humans with heart failure.

Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.

Inhibition of sodium-glucose cotransporter 2 suppresses renal stone formation.

BACKGROUND AND AIMS: Nephrolithiasis is a common renal disease with no effective medication. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, an anti-diabetic agent, have diuretic and anti-inflammatory properties and could prevent nephrolithiasis. Here, we investigated the potential of SGLT2 inhibition against nephrolithiasis using large-scale epidemiological data, animal models, and cell culture experiments. METHODS: This study included the data of diabetic patients (n = 1,538,198) available in the Japanese administrative database and divided them according to SGLT2 inhibitor prescription status. For animal experiments, renal calcium oxalate stones were induced by ethylene glycol in Sprague-Dawley rats, and phlorizin, an SGLT1/2 inhibitor, was used for the treatment. The effects of SGLT2-specific inhibition for renal stone formation were assessed in SGLT2-deficient mice and a human proximal tubular cell line, HK-2. RESULTS: Nephrolithiasis prevalence in diabetic men was significantly lower in the SGLT2 inhibitor prescription group than in the non-SGLT2 inhibitor prescription group. Phlorizin attenuated renal stone formation and downregulated the kidney injury molecule 1 (Kim1) and osteopontin (Opn) expression in rats, with unchanged water intake and urine volume. It suppressed inflammation and macrophage marker expression, suggesting the role of the SGLT2 inhibitor in reducing inflammation. SGLT2-deficient mice were resistant to glyoxylic acid-induced calcium oxalate stone formation with reduced Opn expression and renal damages. High glucose-induced upregulation of OPN and CD44 and cell surface adhesion of calcium oxalate reduced upon SGLT2-silencing in HK-2 cells. CONCLUSION: Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis.

Inhibition of platelet-derived growth factor pathway suppresses tubulointerstitial injury in renal congestion.

OBJECTIVE: Increased central venous pressure in congestive heart failure is responsible for renal dysfunction, which is mediated by renal venous congestion. Pericyte detachment from capillaries after renal congestion might trigger renal fibrogenesis via pericyte-myofibroblast transition (PMT). Platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated in our recently established renal congestion model. This study was designed to determine whether inhibition of the PDGFR pathway could suppress tubulointerstitial injury after renal congestion. METHODS: The inferior vena cava between the renal veins was ligated in male Sprague-Dawley rats, inducing congestion only in the left kidney. Imatinib mesylate or vehicle were injected intraperitoneally daily from 1 day before the operation. Three days after the surgery, the effect of imatinib was assessed by physiological, morphological and molecular methods. The inhibition of PDGFRs against transforming growth factor-ß1 (TGFB1)-induced fibrosis was also tested in human pericyte cell culture. RESULTS: Increased kidney weight and renal fibrosis were observed in the congested kidneys. Upstream inferior vena cava (IVC) pressure immediately increased to around 20 mmHg after IVC ligation in both the imatinib and saline groups. Although vasa recta dilatation and pericyte detachment under renal congestion were maintained, imatinib ameliorated the increased kidney weight and suppressed renal fibrosis around the vasa recta. TGFB1-induced elevation of fibrosis markers in human pericytes was suppressed by PDGFR inhibitors at the transcriptional level. CONCLUSION: The activation of the PDGFR pathway after renal congestion was responsible for renal congestion-induced fibrosis. This mechanism could be a candidate therapeutic target for renoprotection against renal congestion-induced tubulointerstitial injury.

Factors Predicting Tongue Pressure Decline among Community-Dwelling Older Adults: The Takashimadaira Study.

A limited number of longitudinal studies have explored factors contributing to decreases in tongue pressure (TP). This longitudinal study aimed to clarify the factors affecting TP decline among community-dwelling older adults. We followed the Takashimadaira Study participants with a baseline TP ≥ 30 kPa for 2 years. A TP of <30 kPa at follow-up was defined as TP decline. We used Poisson regression with robust standard errors to explore the factors related to TP decline. The studied baseline variables were dental status, sociodemographic characteristics, health behaviors, appetite, medical conditions, physical function, cognitive status, and anthropometric and body composition characteristics. Inverse probability weighting (IPW) was used to adjust for selection bias. Overall, 357 individuals (159 men and 198 women) with a mean (standard deviation) age of 75.9 (4.1) years were included in the analyses. Of these, 59 study participants (16.5%) exhibited TP decline. After adjusting for baseline TP and applying IPW, poor appetite (incident rate ratio [95% confidence interval] = 1.58 [1.01−2.48]), low skeletal muscle mass index (1.66 [1.02−2.70]), and cognitive impairment (1.93 [1.12−3.33]) were associated with TP decline. In conclusion, we demonstrated that baseline appetite, body composition, and cognitive status could predict future TP decline among community-dwelling older adults.

ß-Lactolin improves mitochondrial function in Aß-treated mouse hippocampal neuronal cell line and a human iPSC-derived neuronal cell model of Alzheimer's disease.

Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). ß-Lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine tetrapeptide, has been previously reported to prevent AD-like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of ß-lactolin on neuronal cells and neuronal mitochondrial functions remains unknown. Here, we investigated the effects of ß-lactolin on mitochondrial functions in amyloid ß (Aß)-treated mouse hippocampal neuronal HT22 cells and human induced-pluripotent cell (hiPSC)-derived AD model neurons. Adding ß-lactolin to Aß-treated HT22 cells increased both the oxygen consumption rate and cellular ATP concentrations, suggesting that ß-lactolin improves mitochondrial respiration and energy production. Using high content image analysis, we found that ß-lactolin improved mitochondrial fragmentation, membrane potential, and oxidative stress in Aß-treated cells, eventually preventing neuronal cell death. From a mechanistic perspective, we found that ß-lactolin increased gene expression of mitofusin-2, which contributes to mitochondrial fusion events. Finally, we showed that ß-lactolin improves both mitochondrial morphologies and membrane potentials in hiPSC-derived AD model neurons. Taken together, ß-lactolin improved mitochondrial functions AD-related neuronal cell models and prevented neuronal cell death. The dual function of ß-lactolin on both neuron and microglia marks an advantage in maintaining neuronal health.

Severity of Dementia Is Associated with Increased Periodontal Inflamed Surface Area: Home Visit Survey of People with Cognitive Decline Living in the Community.

No studies have measured the periodontal inflamed surface area in people with dementia, although periodontal disease is a major health issue in this group. This study aimed to determine the relationship between dementia severity and periodontal inflamed surface area. An interdisciplinary team, including a dentist and psychiatrist, conducted an in-home survey of older people living in the community. This cross-sectional study was designed as part of a larger cohort study. The interdisciplinary team visited 198 individuals with cognitive decline. We surveyed the clinical dementia rating, periodontal inflamed surface area, number of teeth, and other health issues. We used multiple linear regression analysis to assess the 75 people who were able to take part in all the visits. Number of teeth (Beta = 0.479, p < 0.001), clinical dementia rating (Beta = 0.258, p = 0.013), and age (Beta = 0.250, p = 0.017) were independently associated with periodontal inflamed surface area after adjusting for biological sex, depression, diabetes, collagen disease, visual disorder, and osteoporosis medication. To make communities more dementia-friendly, we must protect older people with dementia from developing poor oral health, which may require home visits for dental assessment.

Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans.

Previous studies have revealed the importance of inter-tissue communications for lifespan regulation. However, the inter-tissue network responsible for lifespan regulation is not well understood, even in a simple organism Caenorhabditis elegans. To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension. Our tissue-specific knockdown and knockout analyses demonstrated that IIS reduction in neurons and the intestine markedly extended lifespan. DAF-16 activation in neurons resulted in DAF-16 activation in the intestine and vice versa. Our dual gene manipulation method revealed that intestinal and neuronal DAF-16 mediate longevity induced by daf-2 knockout in neurons and the intestine, respectively. In addition, the systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. Collectively, these results highlight the importance of the neuronal DAF-16-to-intestinal DAF-16 communication for organismal lifespan regulation.

The effect of partially hydrolyzed guar gum on preventing influenza infection.

BACKGROUND & AIMS: Seasonal influenza infection in hospitals is a serious problem, and infection prevention is important. We examined retrospectively the effect of prebiotics using partially hydrolyzed guar gum (PHGG) in the prevention of influenza infection. METHODS: Among the patients who were admitted to Hokusei Hospital between April 2017 and March 2019, 522 patients consuming food orally (492 in the convalescent rehabilitation ward and 30 in the long-term care ward) were included in this single-center retrospective cohort study. Patients were divided into two groups: a group continuously taking PHGG (PHGG group; 172 patients in the convalescent rehabilitation ward and 16 patients in the long-term care ward) and a group not taking PHGG (non-PHGG group; 320 patients in the convalescent rehabilitation ward and 14 patients in the long-term care ward). The incidence of influenza during hospitalization, stool pH, and Bristol Stool Form Scale (BSS) at 2 months after admission (2 months after the start of PHGG intake in the PHGG group) were compared between the two groups. In addition, stool pH and BSS were compared between patients who developed influenza and those who did not. RESULTS: A total of 24 patients developed influenza. These patients were from the non-PHGG group (12 in the convalescent rehabilitation ward and 12 in the long-term care ward), with a significant difference in the incidence of influenza between these two sub-groups (p < 0.001). The non-PHGG group had more patients with high stool pH (90th percentile or higher) (p = 0.097, not clinically significant, in the convalescent rehabilitation ward and p < 0.001 in the long-term care ward). This group also had more patients with very poor BSS (score 1 or 7) (p = 0.045 in the convalescent rehabilitation ward and p < 0.001 in the long-term care ward). In addition, patients with influenza onset had high stool pH and very poor BSS regardless of their wards. CONCLUSION: The incidence of influenza was found to be different between patients with and without taking PHGG. Stool pH and BSS were different between patients with and without PHGG intake and those with and without influenza onset, suggesting that PHGG can affect the intestinal environment and thus contribute to reducing the incidence of influenza.

Bitter taste receptor activation by hop-derived bitter components induces gastrointestinal hormone production in enteroendocrine cells.

Matured hop bitter acids (MHBA) are bitter acid oxides derived from hops, widely consumed as food ingredients to add bitterness and flavor in beers. Previous studies have suggested a potential gut-brain mechanism in which MHBA simulates enteroendocrine cells to produce cholecystokinin (CCK), a gastrointestinal hormone which activates autonomic nerves, resulting in body fat reduction and cognitive improvement; however, the MHBA recognition site on enteroendocrine cells has not been fully elucidated. In this study, we report that MHBA is recognized by specific human and mouse bitter taste receptors (human TAS2R1, 8, 10 and mouse Tas2r119, 130, 105) using a heterologous receptor expression system in human embryonic kidney 293T cells. In addition, knockdown of each of these receptors using siRNA transfection partially but significantly suppressed an MHBA-induced calcium response and CCK production in enteroendocrine cells. Furthermore, blocking one of the essential taste signaling components, transient receptor potential cation channel subfamily M member 5, remarkably inhibited the MHBA-induced calcium response and CCK production in enteroendocrine cells. Our results demonstrate that specific bitter taste receptor activation by MHBA drives downstream calcium response and CCK production in enteroendocrine cells. These findings reveal a mechanism by which food ingredients derived from hops in beer activate the gut-brain axis for the first time.

Hop bitter acids containing a ß-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system.

The prevention of age-related cognitive decline and dementia is becoming a high priority because of the rapid growth of aging populations. We have previously shown that hop bitter acids such as iso-α-acids (IAAs) and matured hop bitter acids (MHBAs) activate the vagus nerve and improve memory impairment. Moreover, supplements with MHBAs were shown to improve memory retrieval in older adults. However, the underlying mechanisms have not been entirely elucidated. We aimed to investigate the effects of MHBAs and the common ß-tricarbonyl moiety on memory impairment induced by the activation of microglia and the loss of the noradrenergic system. MHBAs and a model compound with ß-tricarbonyl moiety were administered to LPS-inoculated mice and 5 × FAD Alzheimer's disease (AD) model mice, following the evaluation in behavioral tests and microglial activation. To evaluate the association of noradrenaline with MHBAs effects, mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin that selectively damages noradrenergic projections from the locus coeruleus, were subjected to the behavioral evaluation. MHBAs reduced brain inflammation and improved LPS-induced memory impairment. A model compound possessing the ß-tricarbonyl moiety improved the LPS-induced memory impairment and neuronal loss via the vagus nerve. Additionally, the protective effects of MHBAs on memory impairment were attenuated by noradrenaline depletion using DSP-4. MHBAs suppressed the activation of microglia and improved the memory impairment in 5 × FAD mice, which was also attenuated by noradrenaline depletion. Treatment with MHBAs increased cholecystokinin production from the intestinal cells. Generally, cholecystokinin activates the vagal nerve, which stimulate the noradrenergic neuron in the locus ceruleus. Taken together, our results reveal that food ingredients such as hop bitter acids with a ß-tricarbonyl moiety suppress microglial activation and improve memory impairment induced by inflammation or AD pathology via the activation of the gut-brain axis and noradrenergic system. Supplements with hop bitter acids, including MHBAs, might be a novel approach for the prevention of cognitive decline and dementia.

Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.

BACKGROUND: Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan. METHODS: Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses. RESULTS: Groups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex. CONCLUSION: HCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.

Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue.

Matured hop bitter acids (MHBA) are oxidation products from bitter components in hops, which are used widely as food materials to add flavor and bitterness in beer production. Our previous study has shown that MHBA induces thermogenesis in brown adipose tissue (BAT) via sympathetic nerves in rodents and reduces body fat in healthy adults. However, it is unclear how MHBA affects the sympathetic nervous system. In this study, we demonstrate that MHBA treatment of enteroendocrine cells increases Ca2+ levels and induces the secretion of the gastrointestinal hormone, cholecystokinin (CCK), in a dose-dependent manner. These effects were eliminated by Ca2+ depletion from the medium or blockers of L-type voltage-sensitive Ca2+ channels during pretreatment. Induction of CCK secretion by MHBA was also confirmed using isolated rat small intestines. Elevation of the sympathetic nerve activity innervating BAT (BAT-SNA) and BAT temperature by MHBA administration in rats was blocked by pretreatment with a CCK receptor 1 (CCK1R) antagonist. Moreover, the intraperitoneal injection of CCK fragment elevated BAT-SNA, and this increase was blocked by subdiaphragmatic vagotomy. These results demonstrate that MHBA induces CCK secretion in the gastrointestinal tracts and elevates BAT-SNA via CCK1R and vagal afferent nerves. In addition, MHBA increases BAT temperature via CCK1R. Our findings reveal a novel mechanism of the beneficial metabolic effects of food ingredients.

The relationship between the effect of matured hop extract and physical activity on reducing body fat: re-analysis of data from a randomized, double-blind, placebo-controlled parallel group study.

BACKGROUND: We recently reported that successive ingestion of matured hop extract (MHE), produced by oxidation of hops, results in a reduction of body fat in healthy overweight participants. A combined effect of MHE and physical activity on body fat has not been investigated. Thus, we re-analyzed data from the previous study to explore the relationship between the effect of MHE and walking as an index of physical activity. METHODS: This analysis uses existing data from a randomized, double-blind, placebo-controlled parallel group study in which MHE (active) or placebo was given for 12 w to 200 healthy overweight Japanese, from May to December 2014. Correlation between the change in abdominal fat areas at 12 w and the number of steps taken per day was tested by Spearman's correlation coefficient test. The subjects were stratified using the average number of steps per day of Japanese into walking less and walking more subgroups (WL and WM, respectively) as follows: placebo (WL, n = 43; WM, n = 44) and active (WL, n = 49; WM, n = 42). Reductions in total, visceral, and subcutaneous fat area (TFA, VFA and SFA, respectively) were evaluated. The interaction effect between ingestion (active/placebo) and walking (WL/WM) was analyzed using two-way analysis of variance (ANOVA). RESULTS: There was a significant negative correlation between the change in VFA and daily steps taken in the active group (r = - 0.208, P = 0.048). No significant correlation in TFA or SFA. Although the interaction effect in TFA was not significant, the main effect of ingestion was significant (P = 0.045). In contrast, the interaction effect in VFA was suggested to be synergistic (P = 0.055). CONCLUSION: The results suggested that MHE ingestion combined with light intensity exercise would induce a greater reduction in VFA which would be beneficial for obese or overweight individuals in reducing obesity and obesity-related diseases. TRIAL REGISTRATION: UMIN-CTR UMIN000014185 registered 6 June 2014.

Better Healing of the Exit Site with Negative-Pressure Wound Therapy.

Exit-site infection poses a risk for peritonitis and can shorten peritoneal dialysis (PD) vintage. A loose fit of the skin around the catheter at the exit site can push bacteria surrounding the catheter into the subcutaneous tunnel. Negative-pressure wound therapy (NPWT) has been used to hasten healing of the wound after an operation or to treat pressure ulcers. We hypothesized that NPWT could speed the healing of the exit site and tighten the fit of the skin around the catheter. Using a V.A.C. Therapy system [vacuum-assisted closure (KCI, San Antonio, TX, U.S.A.)], NPWT was therefore applied in 9 patients for 1 - 2 weeks after the PD catheter insertion operation. Results in those patients were compared with results in patients who did not receive NPWT.The healed exit site was classified as either tightly fitted (when the skin was tightly connected around the PD catheter) or loosely fitted (when the skin was not tightly connected around the catheter). The relevant data were retrieved from the medical record and analyzed retrospectively.Patients who received NPWT had a tight exit site after 1 - 2 weeks. Those who did not receive NPWT did not have a tight exit site after 1 - 2 weeks. No bleeding was observed in patients receiving NPWT. Bleeding from the exit site after the catheter insertion operation was observed in 3 patients not receiving NPWT.Because we use a fine trocar to make the subcutaneous catheter tunnel, bleeding from the vasculature can often be observed. That bleeding could be minimized with the application of NPWT. Negative pressure could also hasten wound healing and result in a tight fit of the skin around the catheter within in 1 - 2 weeks compared with the 1 month typically required with the use of conventional film dressings.Negative-pressure wound therapy is beneficial for creating a tight fit of the skin to the catheter within 1 - 2 weeks and might reduce the number of exit-site and tunnel infections, which could result in a reduction in the peritonitis rate.

Pathophysiological and molecular mechanisms involved in renal congestion in a novel rat model.

Increased central venous pressure in congestive heart failure causes renal dysfunction; however, the underlying mechanisms are unclear. We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.

Genetic, acute and subchronic toxicity studies of matured hop extract produced by extraction from heat-treated hops.

It has been demonstrated that successive ingestion of matured hop extract (MHE), produced by extraction from heat-treated hops, results in body fat reduction in animals and humans; however, preclinical safety studies have not been reported. In this study, we conducted in vitro and in vivo safety studies for MHE. Genotoxicity was evaluated using the Ames test, in vitro chromosomal aberration test, and in vivo micronucleus test. To assess acute safety, a single, oral administration of MHE to rats was monitored. Subchronic safety was assessed by repeated feeding with MHE for 90 days. The in vitro chromosomal aberration test was positive at 3,330 µg/mL and 5,000 µg/mL without metabolic activation. However, MHE did not induce any reverse mutation with or without metabolic activation in the Ames test, and no abnormalities were observed at a dose of 2,000 mg/kg body weight in the rat micronucleus test. In the acute and subchronic safety studies, no deaths or toxicological signs were recorded during the observation period. In addition, no changes in body weights, feed/water consumption, clinical signs, ophthalmoscopy, urinalysis, hematology, blood biochemistry, organ weights, or histopathology were observed after repeated administration of MHE. Therefore, the no-observed-adverse-effect-level (NOAEL) of MHE was considered to be over 3,484 and 4,022 mg/kg body weight/day in males and females, respectively. These results indicate that there is no safety concern for MHE in the present preclinical safety study.