Aversion to a High Salt Taste is Disturbed in Patients With CKD.

Introduction: A reduced salt intake is a vital lifestyle modification in the management of hypertension. Initiatives aimed at decreasing the intake of salt are based on the preference by humans for a salt taste. Salt intake behavior appears to be affected by the balance between attraction to a low salt taste and aversion to a high salt taste. However, aversion to a high salt taste has not yet been quantitively investigated in both healthy individuals and patients with chronic kidney disease (CKD). Methods: Assessments of gustatory and aversion thresholds for salt, bitter, sour, and sweet tastes were performed using a stimulant-impregnated test strip in healthy subjects and patients with CKD. Results: In a pilot taste test of 125 healthy subjects, the number of participants with an aversive reaction increased at higher salt concentrations. The threshold for normal taste perception was arbitrarily defined as 10% NaCl, with 47.2% of healthy subjects displaying an aversive reaction. In taste tests performed by 70 patients with CKD, 10% were unable to recognize a salt taste, even at the highest concentration (20% NaCl), suggesting a significant impairment in taste perception in patients with CKD. Only 15.7% of patients with CKD exhibited a normal aversion to NaCl, whereas 78.6% showed the complete loss of aversion to salt. Conclusion: The present results confirmed the anticipated aversive response to a high salt taste in humans and demonstrated its impairment in patients with CKD, implying that patients with CKD have reduced resistance to a high salt intake.

The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression.

The immense public health burden of diabetic kidney disease (DKD) has led to an increase in research on the pathophysiology of advanced DKD. The present study focused on the significance of proinflammatory vascular cell adhesion molecule 1 (VCAM1)+ tubules in DKD progression. A retrospective cohort study of DKD patients showed that the percentage of VCAM1+ tubules in kidney samples was correlated with poor renal outcomes. We established an advanced DKD model by partial resection of the kidneys of db/db mice and demonstrated that it closely resembled the human advanced DKD phenotype, with tissue hypoxia, tubular DNA damage, tissue inflammation, and high tubular VCAM1 expression. Luseogliflozin ameliorated tissue hypoxia and proinflammatory responses, including VCAM1+ expression, in tubules. These findings suggest the potential of tubular VCAM1 as a histological marker for poor DKD outcomes. SGLT2 inhibitors may attenuate tissue hypoxia and subsequent tissue inflammation in advanced DKD, thereby ameliorating tubular injury.

Synthesis of Curved Polycyclic Arenes Embedded with Oxepine and Thiepine Using Ring Expansion Strategy.

A tandem oxidative ring expansion of a six- to seven-membered ring was developed to construct a new class of negatively curved polycyclic arenes embedded with oxepine and thiepine, namely, dibenzo[b,f]phenanthro[9,10-d]oxepine (DBPO) and dibenzo[b,f]phenanthro[9,10-d]thiepine (DBPT), respectively. Mechanistic studies disclosed that an unexpected [4 + 2] cycloadduct formed between the alkene moiety of o-biphenyl-linked methylenexanthenes and o-chloranil serves as a radical cation or a dication equivalent that facilitates the FeCl3-mediated tandem ring expansion process.

Silver-Catalyzed para-Selective Sulfenyl Group Transfer Reactions of N-Sulfenylanilides.

Silver-catalyzed reactions of N-sulfenylanilides afforded the corresponding p-sulfenylanilides in good to high yields with good para selectivity. The transformation has a high compatibility of functional groups, such as ester, bromo, and iodo groups. Mechanistic studies indicate that the rearrangement reaction proceeds through intermolecular transfer of the sulfenyl group.

Usefulness of Percutaneous Drainage in Determining the Causative Microorganism in Patients with Spondylodiscitis: A Retrospective Cross-Sectional Study.

Purpose: To determine the usefulness of CT-guided percutaneous drainage for the causative microorganism detection in patients with spondylodiscitis. Materials and Methods: Data of patients who underwent CT-guided percutaneous drainage for spondylodiscitis from January 2014 to April 2022 were extracted from the radiological database of our hospital and investigated. The administration rate of antibiotics prior to blood culture and CT-guided percutaneous drainage (CTPD) were analyzed. The detection rate of microorganisms via blood culture and CT-guided percutaneous drainage were compared using the Mann-Whitney's U test with the SPSS software. Results: In this study, a total of 30 (20 male and 10 female) patients were analyzed. A total of 13 patients (43%) were administered antibiotics prior to blood culture. Of them, microorganisms were detected via blood culture in only one patient (7%). A total of 25 patients (83%) were administered antibiotics prior to CTPD. Of them, the causative microorganisms in 19 patients (76%) were detected. Overall, the causative microorganism could be detected in 24 out of 26 patients (92%) via CT-guided percutaneous drainage. There was a statistical significance in the detection rate of microorganisms between blood culture and CTPD (P = 0.004) in favor of CTPD. Conclusion: CT-guided percutaneous drainage showed a high positive rate of microorganism detection in patients with spondylodiscitis regardless of antibiotic administration prior to the procedure. CT-guided percutaneous drainage can be a solution for the detection of the causative microorganism in spondylodiscitis patients who received antibiotics before obtaining any culture.

Copper-catalyzed [1,3]-nitrogen rearrangement of O-aryl ketoximes via oxidative addition of N-O bond in inverse electron flow.

The [1,3]-nitrogen rearrangement reactions of O-aryl ketoximes were promoted by N-heterocyclic carbene (NHC)-copper catalysts and BF3·OEt2 as an additive, affording ortho-aminophenol derivatives in good yields. The reaction of substrates with electron-withdrawing substituents on the phenol moiety are accelerated by adding silver salt and modifying the substituent at the nitrogen atom. Density functional theory calculations suggest that the rate-determining step of this reaction is the oxidative addition of the N-O bond of the substrate to the copper catalyst. The negative ρ values of the substituent at both the oxime carbon and phenoxy group indicate that the donation of electrons by the oxygen and nitrogen atoms accelerates the oxidative addition.

Synthesis of meta-Aminophenol Derivatives via Cu-Catalyzed [1,3]-Rearrangement-Oxa-Michael Addition Cascade Reactions.

Cu-catalyzed reactions of N-alkoxy-2-methylanilines and alcohols in the presence of catalytic amounts of IPrCuBr and AgSbF6 afforded the corresponding meta-aminophenol derivatives in good to high yields. These reactions proceed via a [1,3]-rearrangement, in which the alkoxy group migrates from the nitrogen atom to the methyl-substituted ortho position, followed by an oxa-Michael reaction of the resulting ortho-quinol imine intermediate.

Streptozotocin induces renal proximal tubular injury through p53 signaling activation.

Streptozotocin (STZ), an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings, is incorporated into pancreatic ß-cells or proximal tubular epithelial cells through the glucose transporter, GLUT2. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of STZ-treated tubular epithelial cells in vitro showed the activation of the p53 signaling pathway. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transporters. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic ß-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo. Since the cytotoxic effects of STZ against ß-cells were not impaired by dapagliflozin, pretreatment with an SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ.

Peripheral Parenteral Nutrition Solutions and Bed Bath Towels as Risk Factors for Nosocomial Peripheral Venous Catheter-related Bloodstream Infection by Bacillus cereus.

In Japan, China, and Singapore, several studies have reported increased incidences of peripheral venous catheter-related bloodstream infection by Bacillus cereus during the summer. Therefore, we hypothesized that bed bathing with a B. cereus-contaminated "clean" towels increases B. cereus contact with the catheter and increases the odds of contaminating the peripheral parenteral nutrition (PPN). We found that 1) professionally laundered "clean" towels used in hospitals have B. cereus (3.3×104 colony forming units (CFUs) / 25cm2), 2) B. cereus is transferable onto the forearms of volunteers by wiping with the towels (n=9), and 3) B. cereus remain detectable (80∼660 CFUs /50cm2) on the forearms of volunteers even with subsequent efforts of disinfection using alcohol wipes. We further confirmed that B. cereus grow robustly (102 CFUs /mL to more than 106 CFUs /mL) within 24hours at 30°C in PPN. Altogether we find that bed bathing with a towel contaminated with B. cereus leads to spore attachments to the skin, and that B. cereus can proliferate at an accelerated rate at 30°C compared to 20°C in PPN. We therefore highly recommend ensuring the use of sterile bed bath towels prior to PPN administration with catheter in patients requiring bed bathing.

DNA amplification tests at universal pre-admission screening with enhanced precaution strategies for asymptomatic patients with COVID-19.

Objective: To analyse the effect of hospital pre-admission screening and enhanced precaution strategies on the transmission of severe acute respiratory syndrome coronavirus-2. Methods: This retrospective cohort study was conducted over 17 months from 11 May 2020 to 30 September 2021 at a large hospital in Tokyo. Universal DNA amplification tests were conducted during pre-admission screening, and enhanced precaution strategies were implemented for all patients with negative admission tests. The primary outcome was the occurrence of symptomatic coronavirus disease 2019 (COVID-19) in patients after admission. The secondary outcomes were time-series analyses of monthly positive admission test numbers, positive rates, clinical features in positive cases, and clinically confirmed nosocomial transmission. Results: In total, 32,081 patients were screened pre-admission (29,556 asymptomatic patients and 2525 symptomatic patients). Of the asymptomatic patients, 0.11% (n=32) tested positive and were admitted to a designated COVID-19 ward or were not admitted. Among the five inpatients who developed symptomatic COVID-19 during hospitalization, only two cases were related to a single nosocomial transmission. Conclusion: Pre-admission test screening was effective in identifying asymptomatic cases of COVID-19. This allowed administrators to quarantine patients or delay hospital admission. The combination of testing and enhanced precaution strategies for asymptomatic cases of COVID-19 may minimize nosocomial transmission.

Comparison of methylprednisolone pulse vs conventional dexamethasone for adult cases of COVID-19 requiring oxygen; a Japanese retrospective cohort study.

BACKGROUND: Although dexamethasone is an effective treatment in cases of coronavirus disease 2019 (COVID-19) requiring oxygen, the efficacy of methylprednisolone pulse is unclear. We compared the characteristics and outcomes of methylprednisolone pulse to those of dexamethasone. METHODS: We conducted a retrospective cohort study on adult COVID-19 cases requiring oxygen and no invasive mechanical ventilation treated with methylprednisolone pulse (1 g/day for 3 days) or dexamethasone (6 mg/day orally or 6.6 mg/day intravenously for ≥5 days). The primary outcome was intensive care unit (ICU) admission. The secondary outcomes were hospital mortality, length of hospital stay (LoS), duration of oxygen requirement, and requirement for hospital transfer, vasopressor(s), intubation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). RESULTS: Twenty two cases of methylprednisolone pulse and 77 cases of dexamethasone were included. Mask ventilation was more common in the methylprednisolone pulse group (P < 0.001). The proportion of ICU admissions was similar between both groups (P = 0.635). The secondary outcomes of hospital mortality and the requirement for hospital transfer, vasopressor(s), intubation, and CRRT were similar between groups. No cases received ECMO. Median LoS (P = 0.006) and duration of oxygen requirement (P = 0.004) were longer in the methylprednisolone pulse group. CONCLUSIONS: The proportion of ICU admissions was similar between the methylprednisolone pulse and the dexamethasone group. However, more cases in the methylprednisolone pulse group required mask ventilation than in the dexamethasone group, suggesting that some cases benefited from methylprednisolone pulse.

Gold-Catalyzed Intermolecular Alkyne Insertion into the N-S Bond in Sulfenamides.

Gold-catalyzed reactions between sulfenamides and terminal alkynes proceeded via cis-insertion of alkynes into the N-S bond in sulfenamides, affording the corresponding ß-sulfenylenamines in yields up to 90%. Mechanistic studies revealed that the reactions proceeded via nucleophilic attack of the sulfenamide nitrogen atom on the π-activated alkyne, followed by tosylate-assisted intermolecular transfer of the sulfenyl group.

Acute Hydrocephalus Associated with Streptococcus anginosus Meningitis.

Introduction: Meningitis-related acute hydrocephalus is rare, challenging to diagnose, and has a high mortality rate. Case description: Here we describe the case of a 76-year-old patient diagnosed with bacterial meningitis who developed acute hydrocephalus and subsequently died. Discussion: Although meningitis-related acute hydrocephalus is usually non-occlusive, occlusive hydrocephalus may also occur. Moreover, worsening hydrocephalus despite cerebrospinal fluid drainage should prompt a diagnosis of obstructive hydrocephalus. In such conditions, potential management strategies include ventriculoperitoneal shunt and endoscopic third ventriculostomy. Conclusion: In patients with meningitis-related hydrocephalus, worsening despite appropriate antibiotic administration, treatment may be complicated by ventriculitis and obstructive hydrocephalus, which can be fatal. If intracranial pressure is not medically controlled, bilateral decompression craniectomy should be considered as a potential management strategy. LEARNING POINTS: The extreme rarity of obstructive hydrocephalus caused by bacterial meningitis can lead to delayed diagnosis and treatment.Ventriculoperitoneal shunt and endoscopic third ventriculostomy are the indicated management strategies for early diagnosis of obstructive hydrocephalus.Bilateral decompression craniectomy may be an option in such cases.

Proximal tubular epithelia-specific transcriptomics of diabetic mice treated with dapagliflozin.

Based on recent clinical trials using sodium-glucose co-transporter 2 inhibitor (SGLT2i) demonstrating the significant improvement of outcomes of diabetic kidney disease (DKD), the paradigm shift from "glomerulocentric" to "tubule centric" pathophysiology in DKD progression has been highlighted. Several responsible mechanisms for renoprotective effects by SGLT2i have been proposed recently, but the changes in proximal tubule-specific gene expression by SGLT2i in diabetic mice have not been elucidated. We report the analysis of the proximal tubular-specific pathway, demonstrating the downregulation of oxidative phosphorylation in dapagliflozin-treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having a proximal tubule-specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequencing of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated renal cortical tissue hypoxia in db/db mice, which was improved by dapagliflozin administration. This study suggests that dapagliflozin can ameliorate the excessive oxygen and ATP consumption, and subsequent tissue hypoxia in the diabetic kidney, which may explain, in part, the responsible mechanisms of the renoprotective effects of dapagliflozin.

A fatal case of repeated ventricular fibrillation due to torsade de pointes following repeated administration of metoclopramide.

Although metoclopramide has many adverse effects, torsade de pointes (TdP) is rare. We describe a fatal case of repeated ventricular fibrillation due to TdP following repeated administration of metoclopramide. Administration of multiple doses of metoclopramide over a short time to a patient with risk factors for TdP should be avoided.

Changes in the Genotypic Characteristics of Community-Acquired Methicillin-Resistant Staphylococcus aureus Collected in 244 Medical Facilities in Japan between 2010 and 2018: a Nationwide Surveillance.

Although community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide, no nationwide CA-MRSA surveillance has been conducted in Japan to determine the changes in its molecular characteristics over time. We aimed to characterize the molecular epidemiology of Panton-Valentine leucocidin (PVL)-positive CA-MRSA strains collected from across Japan in the past decade. We isolated 1,770 MRSA strains from the skin and pus samples of outpatients of 244 medical facilities in 31 prefectures between 2010 and 2018 (2010, 2012, 2014, 2016, and 2018). Regions, hospitals, and periods in which strains were isolated and patient age group and sex were tabulated. Staphylococcal cassette chromosome mec (SCCmec) typing, detection of virulence factor genes, and antimicrobial susceptibility testing were performed. Whole-genome analysis was performed for the PVL-positive strains isolated in 2018. All strains harbored the mecA gene. Compared to that in 2010, the percentage of SCCmec type IV increased in 2018, with a corresponding increase in the proportion of PVL-positive strains (10% to 26%). Of the isolates obtained in 2018, clonal complex 8 (CC8) was dominant among PVL-positive strains. Core-genome single-nucleotide polymorphism analysis, using whole-genome sequencing, suggested that the CC8 PVL-positive strains spread throughout Japan over the last decade. Furthermore, a unique ST22 clone carrying both the PVL- and toxic shock syndrome toxin-1-encoding genes has emerged. We demonstrated that the molecular epidemiology of CA-MRSA in Japan differs from that in Europe and the United States; thus, it is crucial to monitor the trend of changes in CA-MRSA characteristics in Japan. IMPORTANCE Community-associated MRSA, which is a multidrug-resistant organism and can cause infections in otherwise-healthy individuals, has become a global problem. This paper describes a nationwide surveillance conducted in Japan to investigate changes in molecular epidemiological characteristics of CA-MRSA over the past decade and provides a detailed review of the characteristics of Panton-Valentine leucocidin (PVL)-positive strains isolated in 2018. Although CA-MRSA is rare in Japan to date, we found that the isolation of PVL-positive strains has been increasing over the past decade. In particular, the PVL-positive strains wherein CC8 was dominant exhibited high interstrain similarity, suggesting that a limited number of clones have spread over the past decade. Furthermore, a unique ST22 clone carrying both PVL-encoding and toxic shock syndrome toxin-1-encoding genes has emerged. This study shows that various changes can be observed when molecular epidemiological analysis, combined with next-generation sequencing, is conducted over a long period.

Individual-level social capital and COVID-19 vaccine hesitancy in Japan: a cross-sectional study.

To reduce vaccine hesitancy, it is important to identify factors that can intervene at the individual or community level. Social capital is a possible factor because it is associated with various vaccine hesitancy, such as for measles and influenza. However, limited studies have explored the association between social capital and vaccination for COVID-19, which is an unprecedented pandemic and infodemic. Therefore, this study aimed to clarify the association between social capital and COVID-19 vaccination during the pandemic. This cross-sectional study used quota sampling for an online-based survey. Participants were asked whether they had previously been vaccinated for COVID-19 and their intention to receive a COVID-19 vaccine booster. Social capital was evaluated using three measures (individual-level civic participation, social cohesion, and reciprocity). Multiple logistic regression analysis was performed to clarify the association between social capital and previous COVID-19 vaccination status as well as intention to receive a COVID-19 booster. Participants were 2,313 individuals, of whom 87.2% had received a COVID-19 vaccine; 72.3% intended to obtain a COVID-19 booster. Individuals with any social capital are more likely to receive a COVID-19 vaccination than those with none (OR: 1.73, 95%CI: 1.18-2.54; OR: 1.58, 95%CI: 1.22-2.05; OR: 3.05, 95%CI: 2.15-4.33). These indicators were also associated with the intention to receive a COVID-19 booster. Thus, our results suggest that among the general public, those with individual-level social capital are more likely to receive a COVID-19 vaccination than those with none. Social capital may be a factor that can reduce vaccine hesitancy during a pandemic.

Persistence of Mental Health Deterioration Among People Living Alone During the COVID-19 Pandemic: A Periodically-repeated Longitudinal Study.

BACKGROUND: This longitudinal study aimed to investigate how psychological distress levels changed from early to middle phases of the new coronavirus (COVID-19) pandemic depending on the living arrangements of individuals. METHODS: An internet-based, longitudinal survey of 2,400 Japanese people was conducted every 5-6 weeks between February 2020 and January 2021. The presence of severe psychological distress (SPD) was measured using the Kessler's psychological distress scale. Living arrangements were classified into two groups (ie, living alone or living with others). Mixed-effects logistic regression analysis was performed to assess whether changes in SPD status were different depending on living arrangements. RESULTS: Of 2,400 respondents, 446 (18.5%) lived alone. Although the proportion of SPD in both individuals living alone and those living with others increased to the same extent in the early phase of the pandemic, the distress levels decreased after the early phase of the pandemic in the group living with others, compared with the group living alone, for which SPD remained high. The odds ratio (OR) of developing SPD in interaction term with survey phases tended to be higher among those who lived alone than those who lived with others in Phase 6 (OR 1.89; 95% confidence interval [CI], 0.99-3.64) and Phase 7 (OR 1.88; 95% CI, 0.97-3.63). CONCLUSION: During the COVID-19 pandemic, those living alone are persistently at a higher risk of SPD compared to those living with others. Effective countermeasures targeting those living alone, such as enhancing online communication or providing psychological therapies, are essential.

Direct evidence of proximal tubular proliferation in early diabetic nephropathy.

Kidney hypertrophy is a common clinical feature in patients with diabetes and is associated with poor renal outcomes. Initial cell proliferation followed by cellular hypertrophy are considered the responsible mechanisms for diabetic kidney hypertrophy. However, whether similar responses against hyperglycemia continue in the chronic phase in diabetes is unclear. We performed lineage tracing analysis of proximal tubular epithelia using novel type 2 diabetic mice with a tamoxifen-inducible proximal tubule-specific fluorescent reporter. Clonal analysis of proximal tubular epithelia demonstrated that the labeled epithelia proliferated in type 2 diabetic mice. Based on the histological analysis and protein/DNA ratio of sorted labeled tubular epithelia, there was no evidence of cellular hypertrophy in type 2 diabetic mice. Lineage tracing and histological analyses of streptozocin-induced type 1 diabetes also revealed that cellular proliferation occurs in the chronic phase of type 1 diabetes induction. According to our study, epithelial proliferation accompanied by SGLT2 upregulation, rather than cellular hypertrophy, predominantly occurs in the hypertrophic kidney in both type 1 and type 2 diabetes. An increased number of SGLT2+ tubular epithelia may be an adaptive response against hyperglycemia, and linked to the hyper-reabsorption of sodium and glucose observed in type 2 diabetes patients.