Care needs of caregivers of the elderly with early-stage dementia.

Objective: This study aimed to identify the care needs of family caregivers of elderly patients with early-stage dementia and examine support measures. Materials and Methods: We conducted a self-administered questionnaire survey with 115 primary caregivers of outpatients who visited A City Community General Support Center or B University Hospital Department of Neurology for memory loss consultation. The questionnaire content included demographic characteristics, the care needs scale for caregivers of the elderly with early-stage dementia (Care Needs Scale), and the Japanese short version of the Zarit Burden Interview. The Medical Ethics Committee of Fukuoka University approved this study (approval number: M047). Of the 115 participants, 104 were included in the analysis after excluding 11 respondents with missing data. We divided the participants into a young group (under 65 years of age) and an old group (65 years of age or older) and compared the variables and each scale score using the Mann-Whitney U test. We also compared the correlations between the total score and subscale scores of the Care Needs Scale and each variable, in addition, we performed multiple regression analyses using the total score of the Care Needs Scale as the dependent variable. Results: The young caregivers wanted to know how to take care, prevent deterioration, and deal with symptoms of early-stage dementia. They were trying to balance caregiving with work and housekeeping and reduce the stress and burden of long-term care. Older caregivers were confused about caregiving and wanted someone to talk about their situations. Conclusion: Both groups shared that the family's lack of understanding about caregiving and personal and role strains were associated with the care needs of caregivers of the elderly with early-stage dementia.

Association between having a primary care physician and health behavioral intention in Japan: results from a nationwide survey.

INTRODUCTION: Introducing a primary care physician (Kakaritsuke-I: KI) system to improve the efficiency of the health care system has been controversial in Japan. This study aimed to determine the relevance of KI to an individual's health behavioral intentions. METHODS: We used data from a nationwide, population-based internet survey (N = 5,234) to conduct a cross-sectional regression analysis. Additionally, we used a propensity score matching method to mitigate the potential endogenous biases inherent in the decision to have a KI. RESULTS: KI was positively associated with various behavioral intentions. For example, the probabilities of intending to eat a well-balanced diet and engaging in moderate exercise were 12.8 (95% confidence interval [CI]:9.5-16.1) percentage points and 7.2 (95% CI: 3.9-10.4) percentage points higher, respectively, among those with a KI than among those without a KI. A KI equally increased the likelihood of getting vaccinated against coronavirus (in November 2021) by 7.5 (95% CI: 5.2-9.8) percentage points. CONCLUSIONS: Although further analysis is needed to examine the effect of KI on health, the results of this study suggest the potential benefits of policy measures to promote the KI system.

Ability of older male caregivers to seek help when caring for a wife or mother with dementia living at home.

Objective: We aimed to clarify factors associated with the ability to seek help among older male caregivers who care for women with dementia in their families. Patients and Methods: This information will inform strategies to support their continued provision of long-term care. Participants were 364 male caregivers recruited from three places: The study period was 2017-2018. We obtained ethical approval for this study from the relevant ethics committee. Results: The ability to seek help for care problems among male caregivers was normally distributed. We found that more than 90% of older male caregivers did not actively seek help to resolve care problems, suggesting that older male caregivers had problems with long-term care. In the high score group, health status and the number of emotional support persons in the household were significantly and somewhat strongly positively correlated. The low score group showed a significant and rather weak positive correlation between economic status and health status, and the number of emotional supporters inside and outside the household. Positive correlations for the high score group were self-esteem and depressive symptoms, and self-esteem and resources. Positive correlations for the low score group were self-esteem and depressive symptoms, self-esteem and resources, and resources and depressive symptoms. Conclusion: Male caregivers are more likely to seek help if they are employed or play a role in their community. Nurses also need to support male caregivers with positive words and praise to help them use available support and resources and continue to provide long-term care. It is important for healthcare professionals to observe whether a caregiver presents with depressive symptoms or has long-term care problems because older male caregivers do not seek help. Collaboration between caregivers and medical, long-term care, and welfare professionals is necessary. Direct and timely intervention is needed.

A retrospective study of pulse steroid therapy for acute respiratory failure associated with tuberculosis.

BACKGROUND: Tuberculosis can cause acute respiratory failure, which is associated with a high mortality rate, even in patients receiving effective anti-tuberculosis therapy. We retrospectively analyzed patients with acute respiratory failure associated with tuberculosis who underwent pulse steroid therapy to describe the clinical characteristics and effectiveness of pulse steroid therapy in this condition. METHODS: The medical records of patients admitted to our hospital for culture-proven tuberculosis treatment from April 1, 2017, to March 31, 2022, who received pulse steroid therapy for acute respiratory failure associated with tuberculosis were reviewed. RESULTS: In total, 10 patients were included in this study. Chest computed tomography (CT) revealed diffuse ground-glass opacities and consolidation in these patients. Overall, 70% of the patients (7/10) showed an adjudicated response to pulse steroid therapy, with improved respiratory condition and radiological findings. Three patients died without response to pulse steroid therapy. One patient died of pancreatic cancer after recovering from respiratory failure. The remaining six patients were discharged without supplemental oxygen and completed anti-tuberculosis therapy. CONCLUSIONS: Pulse steroid therapy can lead to dramatic improvements in some patients with acute respiratory failure associated with tuberculosis.

Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity.

Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify antifungal compounds, we screened the RIKEN natural product depository against representative isolates of four major human fungal pathogens. This screen identified NPD6433, a triazenyl indole with broad-spectrum activity against all screening strains, as well as the filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets the enoyl reductase domain of fatty acid synthase 1 (Fas1), covalently inhibiting its flavin mononucleotide-dependent NADPH-oxidation activity and arresting essential fatty acid biosynthesis. Robust Fas1 inhibition kills Candida albicans, while sublethal inhibition impairs diverse virulence traits. At well-tolerated exposures, NPD6433 extended the lifespan of nematodes infected with azole-resistant C. albicans. Overall, identification of NPD6433 provides a tool with which to explore lipid homeostasis as a therapeutic target in pathogenic fungi and reveals a mechanism by which Fas1 function can be inhibited.

Evolutions of Self-Rated Health and Social Interactions during the COVID-19 Pandemic Affected by Pre-Pandemic Conditions: Evidence from a Four-Wave Survey.

The Coronavirus disease 2019 (COVID-19) pandemic has affected individuals' self-rated health (SRH) and social interactions, but their evolution during the pandemic needs further investigation. The present study addressed this issue using longitudinal data from 13,887 observations of 4177 individuals obtained from a four-wave nationwide, population-based survey conducted between January and February 2019 (before the pandemic) and November 2022. We compared the evolutions of SRH and social interactions during the pandemic between individuals who interacted with others before the pandemic and those who did not. Three noteworthy findings were obtained. First, deterioration in SRH in response to the declared state of emergency was concentrated on individuals with no pre-pandemic interaction with others. Second, SRH generally improved during the pandemic, although the improvement was more remarkable among previously isolated individuals. Third, the pandemic has promoted social interactions among previously isolated individuals and reduced such chances among those who previously interacted with others. These findings underscore the importance of pre-pandemic social interactions as key determinants of responding to pandemic-related shocks.

Pre-pandemic social isolation as a predictor of the adverse impact of the pandemic on self-rated health: A longitudinal COVID-19 study in Japan.

Many studies have found adverse effects of the coronavirus disease pandemic on health. Irrespective of being infected by the coronavirus, lockdowns and other measures to restrict mobility have worsened an individual's subjective health assessment. Unlike previous studies, this study examined how pre-pandemic social isolation (in the form of no interaction with others and having no social support) affected the impact of the pandemic on self-rated health in Japan. To this end, we estimated fixed-effects models using 4172 observations of 2086 individuals obtained from a three-wave Internet nationwide survey conducted in January/February 2019 and February 2020 (before the pandemic), in March 2021 (when the pandemic-related state of emergency was effective in four prefectures and just after it was lifted in six prefectures), and in October/November (a full month after the state of emergency was lifted in all prefectures). The state of emergency raised the probability of reporting poor health by 17.8 (95% confidence interval [CI]:1.9-33.8) percentage points among the participants who had not interacted with others before the pandemic, compared with only 0.7 (95% CI: -3.1-4.5) percentage points among other participants. Similar results were obtained in the absence of social support prior to the pandemic. In conclusion, pre-pandemic social isolation was detrimental to health, suggesting that policy measures are needed to avoid social isolation to increase the resilience of public health to external shocks.

Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium.

Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of 13C chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment of the absolute configuration. Janustatins feature a previously unknown pyridodihydropyranone heterocycle and an unusual biological activity consisting of delayed, synchronized cell death at subnanomolar concentrations.

Densification in transparent SiO2 glasses prepared by spark plasma sintering.

Recently, spark plasma sintering (SPS) has become an attractive method for the preparation of solid-state ceramics. As SPS is a pressure-assisted low-temperature process, it is important to examine the effects of temperature and pressure on the structural properties of the prepared samples. In the present study, we examined the correlation between the preparation conditions and the physical and structural properties of SiO2 glasses prepared by SPS. Compared with the conventional SiO2 glass, the SPS-SiO2 glasses exhibit a higher density and elastic modulus, but a lower-height first sharp diffraction peak of the X-ray total structure factor. Micro-Raman and micro-IR spectra suggest the formation of heterogeneous regions at the interface between the SiO2 powders and graphite die. Considering the defect formation observed in optical absorption spectra, reduction reaction mainly affects the densification of SPS-SiO2 glass. Hence, the reaction at the interface is important for tailoring the structure and physical properties of solid-state materials prepared by the SPS technique.

At Which Area Level Does COVID-19 Infection Matter Most for an Individual's Self-Rated Health? A Multilevel Fixed-Effects Model Analysis in Japan.

Several studies have reported the adverse impacts of the COVID-19 pandemic on health outcomes. However, little is known about which area of COVID-19 infection matters most for an individual's subjective health outcomes. We addressed this issue in the present study. We used the longitudinal data of 2260 individuals obtained from a two-wave internet-based nationwide survey conducted in Japan. We estimated the multilevel regression models, which controlled for fixed effects at the individual and prefecture levels, to explain an individual's self-rated health (SRH) based on the reported number of new COVID-19 infection cases at different area levels: prefecture, group of neighboring prefectures, and regional bloc. We found that SRH was highly associated with the average and maximum number of new infection cases among neighboring prefectures or in the regional bloc, but not with those at the prefecture level, if used jointly as explanatory variables. The results suggest that inter-prefectural coordination is needed not only to contain COVID-19 but also to reduce its adverse impact on the subjective health outcomes of residents.

Phenylboronic Ester-Activated Aryl Iodide-Selective Buchwald-Hartwig-Type Amination toward Bioactivity Assay.

In this study, a phenylboronic ester-activated aryl iodide-selective Buchwald-Hartwig-type amination was developed. When the reaction of aryl iodides and aryl/aliphatic amines using Ni(acac)2 is carried out in the presence of phenylboronic ester, the Buchwald-Hartwig-type amination proceeds smoothly to afford the corresponding amines in high yields. This reaction does not proceed in the absence of phenylboronic ester. A wide variety of aryl iodides can be applied in the presence of aryl chlorides and bromides, which remain intact during the reaction. The mechanistic studies of this reaction suggest that the phenylboronic ester acts as an activator for the amines to form the ″ate complex″. Chemical kinetics studies show that the reaction of aryl iodides, base, and Ni(acac)2 follows first-order kinetics, while that of amines and phenylboronic ester follows zero-order kinetics. The bioactivity screening of the corresponding products showed that some amination products exhibit antifungal activity.

The Optimal Anatomical Position and Threshold Temperature of a Temperature Data Logger for Brace-Wearing Compliance in Patients with Scoliosis.

Introduction: Although strict compliance with brace wearing is important for patients with scoliosis, no study has analyzed the most ideal conditions for temperature logger accuracy. We evaluated the optimal brace position and threshold temperature for the logger and determined the reliability of its measurements in patients with scoliosis. Methods: Five temperature loggers were embedded into holes generated at five different brace positions (right scapula, right chest, left chest, lumbar, and abdomen) within the brace. We compared measurement errors at each position using different threshold temperatures to determine the ideal anatomical position and threshold temperature. Under the ideal conditions determined, we calculated the reliability of the temperature logger readings in three healthy participants. Results: Measurement errors (i.e., differences between the actual and logger-recorded brace wearing times) were the lowest at the 28°C and 30°C threshold temperatures when the logger was positioned at the left chest and at 30°C at the abdomen. Among these three temperature/position combinations, we considered the abdomen to be the least affected by the shape of the brace; thus, the placement of the temperature logger at the abdomen using a threshold temperature of 30°C was the most ideal condition. Conclusions: The placement of the temperature logger at the abdomen using a threshold temperature of 30°C was the most ideal condition, with the reliability of the logger being 97.9%±0.9%. This information might be useful for scoliosis management teams, and this temperature logger provides a valuable clinical tool.

Poncet's Disease (Reactive Arthritis Associated with Tuberculosis).

An 82-year-old man with miliary tuberculosis was admitted to our hospital. Approximately six weeks after starting anti-tuberculosis treatment, he complained of pain in the fingers, wrists, and ankles. A histopathological examination of the synovial biopsy revealed nonspecific chronic inflammation with no granulomas. Culture of the biopsy specimen yielded no acid-fast bacilli. Poncet's disease was diagnosed based on the clinical presentation, with no findings suggestive of other diseases. His joint pain rapidly improved with steroid therapy. Tuberculosis can cause arthritis through immune-mediated mechanisms without direct invasion in an entity known as Poncet's disease.

Jerveratrum-Type Steroidal Alkaloids Inhibit ß-1,6-Glucan Biosynthesis in Fungal Cell Walls.

The limited number of available effective agents necessitates the development of new antifungals. We report that jervine, a jerveratrum-type steroidal alkaloid isolated from Veratrum californicum, has antifungal activity. Phenotypic comparisons of cell wall mutants, K1 killer toxin susceptibility testing, and quantification of cell wall components revealed that ß-1,6-glucan biosynthesis was significantly inhibited by jervine. Temperature-sensitive mutants defective in essential genes involved in ß-1,6-glucan biosynthesis, including BIG1, KEG1, KRE5, KRE9, and ROT1, were hypersensitive to jervine. In contrast, point mutations in KRE6 or its paralog SKN1 produced jervine resistance, suggesting that jervine targets Kre6 and Skn1. Jervine exhibited broad-spectrum antifungal activity and was effective against human-pathogenic fungi, including Candida parapsilosis and Candida krusei. It was also effective against phytopathogenic fungi, including Botrytis cinerea and Puccinia recondita. Jervine exerted a synergistic effect with fluconazole. Therefore, jervine, a jerveratrum-type steroidal alkaloid used in pharmaceutical products, represents a new class of antifungals active against mycoses and plant-pathogenic fungi. IMPORTANCE Non-Candida albicans Candida species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents. Here, we report that jervine, a jerveratrum-type steroidal alkaloid, is effective against NCAC and phytopathogenic fungi. Jervine acts on Kre6 and Skn1, which are involved in ß-1,6-glucan biosynthesis. The skeleton of jerveratrum-type steroidal alkaloids has been well studied, and more recently, their anticancer properties have been investigated. Therefore, jerveratrum-type alkaloids could potentially be applied as treatments for fungal infections and cancer.

Carbon Isotope Fractionation during the Formation of CO2 Hydrate and Equilibrium Pressures of 12CO2 and 13CO2 Hydrates.

Knowledge of carbon isotope fractionation is needed in order to discuss the formation and dissociation of naturally occurring CO2 hydrates. We investigated carbon isotope fractionation during CO2 hydrate formation and measured the three-phase equilibria of 12CO2-H2O and 13CO2-H2O systems. From a crystal structure viewpoint, the difference in the Raman spectra of hydrate-bound 12CO2 and 13CO2 was revealed, although their unit cell size was similar. The δ13C of hydrate-bound CO2 was lower than that of the residual CO2 (1.0-1.5‰) in a formation temperature ranging between 226 K and 278 K. The results show that the small difference between equilibrium pressures of ~0.01 MPa in 12CO2 and 13CO2 hydrates causes carbon isotope fractionation of ~1‰. However, the difference between equilibrium pressures in the 12CO2-H2O and 13CO2-H2O systems was smaller than the standard uncertainties of measurement; more accurate pressure measurement is required for quantitative discussion.

Genome-wide screening of genes associated with momilactone B sensitivity in the fission yeast Schizosaccharomyces pombe.

Momilactone B is a natural product with dual biological activities, including antimicrobial and allelopathic properties, and plays a major role in plant chemical defense against competitive plants and pathogens. The pharmacological effects of momilactone B on mammalian cells have also been reported. However, little is known about the molecular and cellular mechanisms underlying its broad bioactivity. In this study, the genetic determinants of momilactone B sensitivity in yeast were explored to gain insight into its mode of action. We screened fission yeast mutants resistant to momilactone B from a pooled culture containing genome-wide gene-overexpressing strains in a drug-hypersensitive genetic background. Overexpression of pmd1, bfr1, pap1, arp9, or SPAC9E9.06c conferred resistance to momilactone B. In addition, a drug-hypersensitive, barcoded deletion library was newly constructed and the genes that imparted altered sensitivity to momilactone B upon deletion were identified. Gene Ontology and fission yeast phenotype ontology enrichment analyses predicted the biological pathways related to the mode of action of momilactone B. The validation of predictions revealed that momilactone B induced abnormal phenotypes such as multiseptated cells and disrupted organization of the microtubule structure. This is the first investigation of the mechanism underlying the antifungal activity of momilactone B against yeast. The results and datasets obtained in this study narrow the possible targets of momilactone B and facilitate further studies regarding its mode of action.

Abatacept for rheumatoid arthritis complicated by disseminated cryptococcosis: a case report.

A 78-year-old man developed disseminated cryptococcosis with central nervous system involvement as encapsulated yeast cells were detected in transbronchial biopsy and skin biopsy specimens, and cerebrospinal fluid. Cryptococcus neoformans was confirmed by culture. He had been treated with low-dose prednisolone and methotrexate for rheumatoid arthritis. He started receiving antifungal therapy with intravenous liposomal amphotericin B followed by oral fluconazole. Methotrexate was discontinued. Approximately 4 months after the course of intravenous liposomal amphotericin B was completed, he complained of pain and swelling of the right wrist, which suggested that rheumatoid arthritis was worsening. Abatacept therapy was initiated along with antifungal therapy, and his symptoms relieved. After 24 months of antifungal therapy, although he was still receiving oral fluconazole, he was doing well and the serum cryptococcal antigen had become negative. Disseminated cryptococcosis is an important opportunistic infection associated with low-dose methotrexate for rheumatoid arthritis. Abatacept therapy may be feasible in strictly selected patients with rheumatoid arthritis complicated with cryptococcosis concomitantly with intensive anti-fungal therapy.

How does area-level deprivation depress an individual's self-rated health and life satisfaction? Evidence from a nationwide population-based survey in Japan.

BACKGROUND: Area-level deprivation is well known to have an adverse impact on mortality, morbidity, or other specific health outcomes. This study examined how area-level deprivation may affect self-rated health (SRH) and life satisfaction (LS), an issue that is largely understudied. METHODS: We used individual-level data obtained from a nationwide population-based internet survey conducted between 2019 and 2020, as well as municipality-level data obtained from a Japanese government database (N = 12,461 living in 366 municipalities). We developed multilevel regression models to explain an individual's SRH and LS scores using four alternative measures of municipality-level deprivation, controlling for individual-level deprivation and covariates. We also examined how health behavior and interactions with others mediated the impact of area-level deprivation on SRH and LS. RESULTS: Participants in highly deprived municipalities tended to report poorer SRH and lower LS. For example, when living in municipalities falling in the highest tertile of municipality-level deprivation as measured by the z-scoring method, SRH and LS scores worsened by a standard deviation of 0.05 (p < 0.05) when compared with those living in municipalities falling in the lowest tertile of deprivation. In addition, health behavior mediated between 17.6 and 33.1% of the impact of municipality-level deprivation on SRH and LS, depending on model specifications. CONCLUSION: Results showed that area-level deprivation modestly decreased an individual's general health conditions and subjective well-being, underscoring the need for public health policies to improve area-level socioeconomic conditions.

Prediction of the duration needed to achieve culture negativity in patients with active pulmonary tuberculosis using convolutional neural networks and chest radiography.

BACKGROUND: We aimed to predict the duration needed to achieve culture negativity in patients with active pulmonary tuberculosis using convolutional neural networks (CNNs) and chest radiography. METHODS: Medical records were searched for eligible patients with culture-confirmed active pulmonary tuberculosis. The eligible patients were randomly assigned to the training dataset group (N = 180) and the validation dataset group (N = 59). Posteroanterior X-ray radiographs in the standing position were obtained at diagnosis. The image data were augmented by a factor of 10 by randomly shifting and rotating the original image. Thus, 1800 images (112 × 112 pixels, 8-bit grayscale) from 180 patients in the training dataset group were used for training the CNN model. The model performance was evaluated on the validation dataset. RESULTS: The values predicted by the CNN model were significantly associated with the actual values (Pearson's correlation coefficient 0.392, p = 0.002). The mean absolute error was 18.0. The visualization of the layer outputs suggested that the CNN model recognized some of the chest radiographic findings that were useful in predicting the duration needed to achieve culture negativity. CONCLUSIONS: The CNN model was useful for predicting the duration needed to achieve culture negativity in active pulmonary tuberculosis, although the accuracy was unsatisfactory. This study suggests that chest radiography findings are as important as other clinical factors for prediction and could be learned by the machine.