Pulmonary Nocardiosis Due to Nocardia exalbida Infection Following Living-donor Liver Transplantation.

Nocardia exalbida, an uncommon Nocardia, was first identified in 2006. We herein report a 70-year-old man with pulmonary nocardiosis caused by N. exalbida after living-donor liver transplantation. We also review 11 previously reported cases of N. exalbida infections. To our knowledge, there are no case reports available on nocardiosis consequent to N. exalbida infection following transplantation, thus highlighting the importance of identifying bacterial species for the successful management of infection.

Ingesting carbonated water post-exercise in the heat transiently ameliorates hypotension and enhances mood state.

The objective was to assess if post-exercise ingestion of carbonated water in a hot environment ameliorates hypotension, enhances cerebral blood flow and heat loss responses, and positively modulates perceptions and mood states. Twelve healthy, habitually active young adults (five women) performed 60 min of cycling at 45% peak oxygen uptake in a hot climate (35°C). Subsequently, participants consumed 4°C carbonated or non-carbonated (control) water (150 and 100 mL for males and females regardless of drink type) at 20 and 40 min into post-exercise periods. Mean arterial pressure decreased post-exercise at 20 min only (P = 0.032) compared to the pre-exercise baseline. Both beverages transiently (∼1 min) increased mean arterial pressure and middle cerebral artery mean blood velocity (cerebral blood flow index) regardless of post-exercise periods (all P ≤ 0.015). Notably, carbonated water ingestion led to greater increases in mean arterial pressure (2.3 ± 2.8 mmHg vs. 6.6 ± 4.4 mmHg, P < 0.001) and middle cerebral artery mean blood velocity (1.6 ± 2.5 cm/s vs. 3.8 ± 4.1 cm/s, P = 0.046) at 20 min post-exercise period compared to non-carbonated water ingestion. Both beverages increased mouth exhilaration and reduced sleepiness regardless of post-exercise periods, but these responses were more pronounced with carbonated water ingestion at 40 min post-exercise (mouth exhilaration: 3.1 ± 1.4 vs. 4.7 ± 1.7, P = 0.001; sleepiness: -0.7 ± 0.91 vs. -1.9 ± 1.6, P = 0.014). Heat loss responses and other perceptions were similar between the two conditions throughout (all P ≥ 0.054). We show that carbonated water ingestion temporarily ameliorates hypotension and increases the cerebral blood flow index during the early post-exercise phase in a hot environment, whereas it enhances mouth exhilaration and reduces sleepiness during the late post-exercise phase.

Technical Efficiency of Prevention Services for Functional Dependency in Japan's Public Long-term Care Insurance System: An Ecological Study.

BACKGROUND: Public long-term care insurance (LTCI) systems can promote equal and wider access to quality long-term care. However, ensuring the financial sustainability is challenging owing to growing care demand related to population aging. To control growing demand, Japan's public LTCI system uniquely provided home- and community-based prevention services for functional dependency for older people (ie, adult day care, nursing care, home care, functional screening, functional training, health education, and support for social activities), following nationwide protocols with decentralized delivery from 2006 until 2015. However, evaluations of the effects of these services have been inconclusive. METHODS: We estimated the marginal gain and technical efficiency of local prevention services using 2009-2014 panel data for 474 local public insurers in Japan, based on stochastic frontier analysis. The outcome was the transformed sex-and age-adjusted ratio of the observed to expected number of individuals aged ≥65 years certified for moderate care. Higher outcome values indicate lower population risk of moderate functional dependency in each region in each year. The marginal gains of the provided quantities of prevention services as explanatory variables were estimated, adjusting for regional medical and welfare access, care demand and supply, and other regional factors as covariates. RESULTS: Prevention services (except functional screening) significantly reduced the population risk of moderate functional dependency. Specifically, the mean changes in outcome per 1% increase in adult day care, other nursing care, and home care were 0.13%, 0.07%, and 0.04%, respectively. The median technical efficiency of local public insurers was 0.94 (interquartile range: 0.89-0.99). CONCLUSION: These findings suggest that population-based services with decentralized local operation following standardized protocols could achieve efficient prevention across regions. This study could inform current discussions about the range of benefit coverage in public LTCI systems by presenting a useful option for the provision of preventive benefits.

Risk of Urogenital Bacterial Infection with Sodium-Glucose Cotransporter-2 Inhibitors: A Retrospective Cohort Study Using a Claims Database.

INTRODUCTION: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan. METHODS: In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18 years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model. RESULTS: We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51 years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83-0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03-1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61-1.81). CONCLUSIONS: SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks.

Successful use of methylene blue for catecholamine-refractory vasoplegic shock due to metformin intoxication: A case report and literature review.

Background: Severe metformin intoxication can lead to lactic acidosis and vasoplegic shock, for which the optimal management strategy remains uncertain, especially in cases of severe circulatory collapse. Case Presentation: A 45-year-old diabetic woman on metformin therapy presented with impaired consciousness and seizures. She had experienced a cardiac arrest and undergone extracorporeal cardiopulmonary resuscitation. Blood gas analysis showed severe lactic acidosis. A 71-g metformin packet was found at the patient's home, suggesting an overdose. Despite extracorporeal support and blood purification, severe lactic acidosis and hypotension persisted. Methylene blue was administered 32 h from the onset, which improved her metabolic and circulatory status. We examined her blood sample throughout the case to check the transition of metformin blood concentration. Conclusion: Methylene blue may be beneficial for severe metformin toxicity, regardless of the blood concentration of metformin and the time since intoxication. However, further research is needed to establish its optimal use and effectiveness.

The impact of social isolation on functional disability in older people: A multi-cohort study.

OBJECTIVES: We assessed the relationship between social isolation and functional disability in older people. DESIGN: Comparison of longitudinal cohort studies. SETTING AND PARTICIPANTS: Harmonised longitudinal datasets from the United States, England, European countries, Japan, Korea, China and Hong Kong. METHODS: Social isolation was operationalised as a composite score with five domains, such as marital status, living alone, and social contact with others. Functional disability was defined as whether the cohort participant had any difficulty in activities of daily living (ADL). In each dataset, we used robust Poisson regression models to obtain the relative risks (RRs) and the corresponding 95 % confidence intervals (CI). We combined the RRs to synthesize a pooled estimate using meta-analysis with random-effects models. RESULTS: Overall, the social isolation composite score was not associated with ADL disability (pooled RR = 1.05, 95 % CI [0.97-1.14], n = 40,119). Subgroup analysis suggested social isolation composite score was associated with ADL disability in Asian regions (pooled RR = 1.09, 95 % CI [1.02, 1.16], but not in Western regions (pooled RR = 1.01, 95 % CI [0.96, 1.07]). The relationships between different domains of social isolation and ADL disability were heterogeneous, except that no participation in any social clubs or religious groups was consistently associated with ADL disability (pooled RR = 1.12, 95 % CI [1.04, 1.21]). CONCLUSION: Targeting social isolation may prevent decline in functional abilities in older adults, providing an avenue to active and healthy ageing. Nonetheless, interventions tackling social isolation should tailor to the unique cultural and social underpinnings. A limitation of the study is that reverse causality could not be ruled out definitively.

No improvement in mortality among critically ill patients with carbapenems as initial empirical therapy and more detection of multi-drug resistant pathogens associated with longer use: a post hoc analysis of a prospective cohort study.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Acute muscle loss assessed using panoramic ultrasound in critically ill adults: a prospective observational study.

PURPOSE: Panoramic ultrasound is one of the recently introduced ultrasound evaluation techniques. We herein examined the relationship between the cross-sectional area of the rectus femoris muscle on panoramic ultrasound and its volume based on the gold standard computed tomography (CT) evaluation. METHODS: This was a single-center prospective observational study. A panoramic ultrasound assessment of the cross-sectional area of the rectus femoris muscle and a simple CT evaluation of its volume were performed on days 1 and 7 of hospitalization. Physical functions were assessed at discharge. RESULTS: Twenty patients were examined. The rate of change in the cross-sectional area of the rectus femoris muscle on panoramic ultrasound correlated with that in its volume on CT (correlation coefficient 0.59, p = 0.0061). In addition, a correlation was observed between the absolute value for the rectus femoris muscle cross-sectional area on panoramic ultrasound and physical functions at discharge. Rectus femoris muscle distances did not correlate with either. CONCLUSION: In the acute phase of critical illness, the cross-sectional area of the rectus femoris muscle on panoramic images correlated with its volume on CT and, thus, it is a valid method for assessing muscle mass.

Effects of mechanical insufflation-exsufflation on ventilator-free days in intensive care unit subjects with sputum retention; a randomized clinical trial.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) facilitates extubation. However, its potential to reduce the duration of ventilator use remains unclear. Therefore, the present study investigated whether the use of MI-E shortened the duration of mechanical ventilation in patients with high sputum retention. METHODS: A randomized open-label trial was conducted at a single intensive care unit (ICU) in Japan between November 2017 and June 2019. Ventilated subjects requiring suctioning at least once every hour due to sputum retention were randomly assigned to the MI-E group or conventional care group. The primary endpoint was the number of ventilator-free days on day 28. Secondary endpoints were ventilator days in surviving subjects, the length of ICU stay, and mortality and tracheostomy rates among survivors. RESULTS: Forty-eight subjects (81% males) with a median age of 72 years (interquartile range [IQR], 65-85 years) were enrolled. There were 27 subjects in the MI-E group and 21 in the control group. The median number of ventilator-free days was 21 (IQR, 13-24) and 18, respectively (IQR, 0-23) (P = .38). No significant differences were observed in the ICU length of stay (median, 10 days (IQR, 7-12) vs 12 days (IQR, 6-15); P = .31), mortality rate (19% vs 15%; odds ratio [OR], 1.36 [0.28-6.50]; P = .69), or tracheostomy rate among survivors (14% vs 28%; OR, 0.40 [0.08-1.91]; P = .25). CONCLUSION: In ventilated subjects in the ICU with high sputum retention, the use of MI-E did not significantly increase the number of ventilator-free days over that with conventional care.

Association between Sense of Coherence, Disease-Specific Symptoms, and Health-Related Quality of Life among Japanese Patients with Ulcerative Colitis: A Cross-Sectional Study.

INTRODUCTION: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). METHODS: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested. RESULTS: SOC was positively and independently associated with HRQOL (Mental Health: ß = 0.43, 95% confidence interval [CI] = 0.24-0.61, p < 0.001; General Health: ß = 0.41, 95% CI = 0.23-0.59, p < 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: ß = -0.0082, 95% CI = -0.017 to 0.00064, p = 0.07; that of FIQL by SOC: ß = -0.0052, 95% CI = -0.011 to 0.0010, p = 0.10). CONCLUSIONS: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC.

Kluyvera georgiana Bacteremia Due to Acute Cholangitis: A Report of the First Known Case and a Literature Review.

We herein present the first known case of bacteremia caused by Kluyvera georgiana in a 67-year-old female undergoing chemotherapy for recurrent pancreatic cancer. The patient underwent choledochojejunotomy and thereafter developed ascending cholangitis. The diagnosis of K. georgiana was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A literature review of Kluyvera spp. infections indicated potential risk factors including an underlying malignancy and immunosuppression. Although Kluyvera spp. infections are typically sensitive to antibiotics, multidrug resistance is possible. This case highlights the importance of the early diagnosis and treatment of K. georgiana and its associated risk factors.

A case of hypervirulent K1-ST23 Klebsiella pneumoniae endocarditis and papillary muscle rupture secondary to multiple site abscesses.

Hypervirulent Klebsiella pneumoniae (hvKP) causes multisite infections and abscesses. However, endocarditis is a rare presentation of hvKP infection. Herein, we report a case of K. pneumoniae native valve infective endocarditis secondary to community-acquired liver and prostate abscesses. The patient developed papillary muscle rupture, leading to mitral regurgitation, and underwent emergent mitral valve replacement. The diagnosis of endocarditis was confirmed microbiologically and histologically. The causative strain belonged to the hypermucoid K1 capsular genotype and possessed the rmpA gene. The genome sequence was deposited in GenBank under the accession number JAQZBZ000000000.

Astaxanthin: Past, Present, and Future.

Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects. Originally recognized primarily for its role in imparting the characteristic red-pink color to various organisms, AX is currently experiencing a surge in interest and research. The growing body of literature in this field predominantly focuses on AXs distinctive bioactivities and properties. However, the potential of algae-derived AX as a solution to various global environmental and societal challenges that threaten life on our planet has not received extensive attention. Furthermore, the historical context and the role of AX in nature, as well as its significance in diverse cultures and traditional health practices, have not been comprehensively explored in previous works. This review article embarks on a comprehensive journey through the history leading up to the present, offering insights into the discovery of AX, its chemical and physical attributes, distribution in organisms, and biosynthesis. Additionally, it delves into the intricate realm of health benefits, biofunctional characteristics, and the current market status of AX. By encompassing these multifaceted aspects, this review aims to provide readers with a more profound understanding and a robust foundation for future scientific endeavors directed at addressing societal needs for sustainable nutritional and medicinal solutions. An updated summary of AXs health benefits, its present market status, and potential future applications are also included for a well-rounded perspective.

General health literacy, COVID-19-related health literacy, and protective behaviors: evidence from a population-based study in Japan.

Introduction: Health literacy (HL) can be regarded as a key element of non-pharmaceutical interventions used in emergency responses. The present study aimed to determine the associations of combinations of general HL and COVID-19-related HL with COVID-19 protective behaviors and healthy lifestyle behaviors. Methods: A questionnaire survey was conducted from December 2020 to January 2021 among residents in Japanese metropolitan areas. Valid responses were received from 1,443 residents. The levels of HL were categorized into four groups: low level in both HLs (reference), high level in general HL only, high level in COVID-19-related HL only, and high level in both HLs. The total scores of eight COVID-19 protective behaviors were dichotomized into low and high adherence. Healthy lifestyle behaviors included healthy and balanced diet, adequate sleep, and regular exercise. Poisson regression analyses were conducted to examine the associations between the HL groups and high adherence to COVID-19 protective behaviors. Results: High level in COVID-19-related HL only was associated with high adherence to COVID-19 protective behaviors [prevalence ratio (PR), 1.25; 95% confidence interval (CI), 1.09-1.45], while high level in general HL only was associated with healthy and balanced diet (PR, 1.49; 95% CI, 1.04-2.13), adequate sleep (PR, 1.46; 95% CI, 1.02-2.10), and regular exercise (PR, 2.00; 95% CI, 1.29-3.13). High level in both HLs showed the highest prevalence of high adherence to COVID-19 protective behaviors and healthy lifestyle behaviors. Conclusion: These findings indicate that COVID-19-related HL and general HL can both be considered to enhance protective behaviors.

Explaining Variations in Long-term Care Use and Expenditures Under the Public Long-term Care Insurance Systems: A Case Study Comparison of Korea and Japan.

BACKGROUND: Establishing universal coverage of formal long-term care (LTC) services is an urgent policy need for aging populations that requires efficient management of quality and financing. Although current variation in LTC service use between and within countries suggests the potential for improvement by efficient management, this topic remains underexamined. We aimed to identify the sources of variance in LTC use and expenditures through a unique cross-country comparison of Japan and South Korea, which have formal public LTC insurance (LTCI) schemes that are analogous but have unique operational and demographic structures. METHODS: Taking administrative regions as the unit of analysis, we assembled data on the LTC utilization rate of people aged ≥65 years, and expenditures per recipient from 2013 to 2015 as the outcome variables. Explanatory variables included demand-related factors, such as regional demographic and economic conditions, and supply characteristics derived from existing public databases. We conducted weighted least squares regression with fixed effects for the pooled data and used Blinder-Oaxaca decomposition to identify sources of outcome variance between the two countries. RESULTS: The average LTC utilization rate was 6.8% in Korea and 18.2% in Japan. Expenditures per recipient were approximately 1.4 times higher in Japan than in Korea. The difference in the utilization rate was mostly explained by between-country differences in supply- and demand-related factors, whereas the difference in expenditures per recipient was largely attributed to unobserved country-specific factors. CONCLUSION: The current findings suggest that LTC utilization is determined largely by the demographic and functional characteristics of older people, whereas expenditures are more likely affected by institutional factors such as the insurance governance scheme and the policy choice of the target population segment and coverage. The results suggest that strategic choice of LTC institutional schemes is required to ensure financial sustainability to meet changing demands caused by population aging.

Impact of Persistent Inflammation, Immunosuppression, and Catabolism Syndrome during Intensive Care Admission on Each Post-Intensive Care Syndrome Component in a PICS Clinic.

BACKGROUND: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is known as a prolonged immunodeficiency that occurs after severe infection. Few studies have demonstrated a direct relationship between PIICS and physical dysfunction in post-intensive care syndrome (PICS). We herein investigated how each component of PICS was affected by the diagnosis of PIICS during hospitalization and examined the relationship between PIICS and PICS using PICS assessments performed at the Hitachi General Hospital PICS Clinic. METHODS: The 273 patients who visited the PICS clinic at one month after discharge from the ICU at Hitachi General Hospital were included in the study. We used the diagnostic criteria for PIICS described in previous studies. At least two of the following blood test values on day 14 of hospitalization had to be met for a diagnosis of PIICS: C-reactive protein (CRP) > 2.0 mg/dL, albumin (Alb) < 3.0 g/dL, and lymphocytes (Lym) < 800/µL. Blood test values closest to day 14 out of 11-17 days of hospitalization were used. The primary outcome was a Barthel Index (BI) < 90, while secondary outcomes were the results of various PICS assessments, including mental and cognitive impairments, performed at the PICS clinic. We supplemented missing data with multiple imputations by chained equations. We performed a nominal logistic regression analysis with age, sex, BMI, SOFA, and the presence of PIICS as variables for BI < 90. RESULTS: Forty-three out of two hundred seventy-three PICS outpatients met the diagnostic criteria for PIICS during hospitalization. In comparisons with non-PIICS patients, significantly higher severity scores for APACHE II and SOFA and a longer hospital stay were observed in PIICS patients, suggesting a higher clinical severity. The primary outcome, BI, was lower in the PIICS group (97.5 (58.5, 100) vs. 100 (95, 100), p = 0.008), as were the secondary outcomes (FSS-ICU: 35 (31, 35) vs. 35 (35, 35), MRC score: 55 (50.25, 58) vs. 58 (53, 60), grip strength: 16.45 (9.2, 25.47) vs. 20.4 (15.3, 27.7)). No significant differences were noted in mental or cognitive function assessments, such as HADS, IES-R, and SMQ. A multivariable analysis supplemented with missing data revealed that PIICS (odds ratio: 1.23 (1.08-1.40 p = 0.001) and age (odds ratio: 1.007 (1.004-1.01), p < 0.001) correlated with BI < 90, independent of clinical severity such as sequential organ failure assessment (SOFA). Similar results were obtained in the sensitivity analysis excluding missing data. CONCLUSIONS: The present study revealed a strong relationship between PIICS and post-discharge PICS physical dysfunction in patients requiring intensive care.

Effects of Algal Extracellular Polysaccharides on the Formation of Filamentous Manganese Oxide Particles in the Near-Bottom Layer of Lake Biwa.

Filamentous manganese (Mn) oxide particles, which occur in the suboxic zone of stratified waterbodies, are important drivers of diverse elemental cycles. These particles are considered to be bacteriogenic; despite the importance of biogeochemical implications, however, the environmental factor responsible for their formation has not been identified. The aim of this study was to demonstrate the involvement of algal extracellular polysaccharides in Mn oxide particle formation. Based on this study of laboratory cultures of a model Mn(II)-oxidizing bacterium, the supply of algal extracellular mucilage was shown to stimulate Mn(II) oxidation and thus the production of filamentous Mn oxide particles. This observation was consistent with the results obtained for naturally occurring particles collected from a near-bottom layer (depth of approximately 90 m) in the northern basin of Lake Biwa, Japan, that is, most Mn particles resembling δ-MnO2 were associated with an extracellular mucilage-like gelatinous matrix, which contained dead algal cells and was lectin-stainable. In the lake water column, polysaccharides produced by algal photosynthesis sank to the bottom layer. The analysis of the quality of water samples, which have been collected from the study site for 18 years, reveals that the annual average total phytoplankton biovolume in the surface layer correlates with the density of filamentous Mn particles in the near-bottom layer. Among different phytoplankton species, green algae appeared to be the key species. The results of this study suggest that algal extracellular polysaccharides serve as an important inducer for the formation of filamentous Mn oxide particles in the near-bottom layer of the northern basin of Lake Biwa.

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study.

BACKGROUND: Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study. METHODS: Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 µg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events. RESULTS: Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%). CONCLUSIONS: Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial.

OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicentre randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; P = 0.022). Serious adverse events were not observed in either group. Phlebitis occurred in ca. 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

Waning cellular immune responses and predictive factors in maintaining cellular immunity against SARS-CoV-2 six months after BNT162b2 mRNA vaccination.

Several clinical trials have shown that the humoral response produced by anti-spike antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines gradually declines. The kinetics, durability and influence of epidemiological and clinical factors on cellular immunity have not been fully elucidated. We analyzed cellular immune responses elicited by BNT162b2 mRNA vaccines in 321 health care workers using whole blood interferon-gamma (IFN-γ) release assays. IFN-γ, induced by CD4 + and CD8 + T cells stimulated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike epitopes (Ag2), levels were highest at 3 weeks after the second vaccination (6 W) and decreased by 37.4% at 3 months (4 M) and 60.0% at 6 months (7 M), the decline of which seemed slower than that of anti-spike antibody levels. Multiple regression analysis revealed that the levels of IFN-γ induced by Ag2 at 7 M were significantly correlated with age, dyslipidemia, focal adverse reactions to full vaccination, lymphocyte and monocyte counts in whole blood, Ag2 levels before the second vaccination, and Ag2 levels at 6 W. We clarified the dynamics and predictive factors for the long-lasting effects of cellular immune responses. The results emphasize the need for a booster vaccine from the perspective of SARS-CoV-2 vaccine-elicited cellular immunity.