Impact of long-hours family caregiving on non-fatal coronary heart disease risk in middle-aged people: Results from a longitudinal nationwide survey in Japan

AimThe effects of family caregiving, especially long-hours caregiving, on coronary heart disease (CHD) are debatable. We examined the impact of family caregiving on incident non-fatal CHD.MethodsWe used data from the Longitudinal Survey of Middle-Aged and Elderly Persons from 2005 to 2010, a nationwide panel survey for Japanese people aged 50–59 years in 2005 (baseline). After we excluded non-respondents and people with missing key variables at baseline, 25 121 individuals without CHD, stroke or cancer were followed up for a mean of 4.6 years. The exposure was assessed at baseline by three indicators: (i) family caregiving; (ii) hours spent caregiving; and (iii) kinship type of care recipient. The non-fatal CHD incidence was identified according to questionnaire responses from 2006 to 2010.ResultsCox\u27s proportional hazards analysis did not show a statistically significant association between family caregiving and incident non-fatal CHD (hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.92–1.40). Caregivers who spent 20–69 h per week on care showed a statistically significant increased risk for non-fatal CHD (HR 1.78, 95% CI 1.23–2.58) compared with non-caregivers; whereas this increased risk was statistically significant only among women (HR 1.98, 95% CI 1.27–3.08), but not among men (HR 1.35, 95% CI 0.67–2.71). Kinship type of care recipient did not make a significant difference to the effects of family caregiving on incident non-fatal CHD.ConclusionsLong-hours family caregiving could be an independent risk factor for incident non-fatal CHD among middle-aged women in Japan. Geriatr Gerontol Int 2017; 17: 2109–2115

Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development

AbstractNotch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development

Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues

The version of record of this article, first published in Analytical and Bioanalytical Chemistry, is available online at Publisher’s website: https://doi.org/10.1007/s00216-024-05477-5.Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI

Measurements of ultrafast dissociation in resonant inelastic x-ray scattering of water

There has been a discussion on the interpretation of the resonant inelastic x-ray scattering (RIXS) spectra of liquid water in terms of either different structural environments or that core hole dynamics can generate well-resolved dissociative spectral components. We have used RIXS with high resolution in the OH stretch vibration energy part, at extremely high overtones going toward the continuum of full OH bond breakage, to identify the amount of dissociative contributions in the valence band RIXS spectra at different excitation energies. We observe that at low excitation energies, corresponding to population of states with strongly antibonding character, the valence band RIXS spectra have a large contribution from a well-resolved dissociative feature. Instead, at higher excitations, this spectral component diminishes and becomes a weak structure on the high-energy side of one of the spectral peaks related to the 1b1 state from tetrahedral configurations. This result brings both interpretations to be essential for the understanding of RIXS spectra of liquid water

Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study

Background The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). Methods In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. Results The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). Conclusion As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN

Characteristics and in-hospital mortality of patients with COVID-19 from the first to fifth waves of the pandemic in 2020 and 2021 in the Japanese Medical Data Vision database

Objectives We aimed to describe patient characteristics, healthcare utilization, and in-hospital mortality among patients with COVID-19 in Japan across waves. Methods Using a large-scale hospital-based database, we identified patients hospitalized for COVID-19 in the first (January–June 2020), second (June–October 2020), third (October 2020–February 2021), fourth (March–June 2021), and fifth (June–December 2021) waves. We summarized patient characteristics, healthcare utilization, and in-hospital mortality during each wave and performed multivariable logistic regression analyses for in-hospital mortality. Results From the first to fifth waves, the number of patients (mean age ± standard deviation, years) was 2958 (61.2 ± 22.8), 7981 (55.6 ± 25.3), 18,788 (63.6 ± 22.9), 17,729 (60.6 ± 22.6), and 23,656 (51.2 ± 22.3), respectively. There were 190 (6.4%), 363 (4.5%), 1261 (6.7%), 1081 (6.1%), and 762 (3.2%) in-hospital deaths, respectively. The adjusted odds ratios for in-hospital deaths (95% confidence interval) were 0.78 (0.65–0.95), 0.94 (0.79–1.12), 0.99 (0.84–1.18), 0.77 (0.65–0.92), in the second to fifth waves, respectively, compared with the first wave. Conclusions In-hospital COVID-19 mortality improved from the first to the second wave; however, during the third and fourth waves, mortality was as serious as in the first wave. Although in-hospital mortality during the fifth wave improved, careful monitoring is needed for upcoming waves, considering changing patient and viral characteristics