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Abstract Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status. Methods Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values. Results Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively. Conclusions Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status.

Introduction: In pharmacotherapy for inflammatory bowel disease (IBD), good medication adherence is necessary to control the condition. However, some patients show poor adherence. Pharmacists need to provide appropriate medication guidance to improve medication adherence. Community pharmacists often have to provide medication guidance in case of insufficient patient information because of varying affiliations. Therefore, to help improve medication adherence in patients with IBD and establish cooperation between community and hospital pharmacies, we investigated the awareness of IBD among pharmacists and the actual status of pharmacist-led medication guidance for patients with IBD. Methods: This study comprised a knowledge test for IBD and a survey of medication guidance for IBD in the form of questionnaires, which were administered to pharmacists using web forms. Results: Community pharmacy affiliation (p < 0.01) and having no experience in medication guidance for IBD (p < 0.01) contributed to low scores in the IBD knowledge test. There was a difference in the correct answer rate for interactions or screening tests prior to medication administration between community and hospital pharmacists. Medication guidance consultations involving residual drug adjustment (p < 0.01), confirmation of symptoms (p < 0.01), prescription from other hospitals (p = 0.04), therapeutic effects (p = 0.04), and confirmation of medication adherence were more common among community pharmacists than among hospital pharmacists. Cooperation between community and hospital pharmacies was most commonly achieved through tracing reports or personal medication handbooks. Conclusion: Improving pharmacists’ awareness of IBD and sharing information are important to facilitate cooperation between community and hospital pharmacists to improve medication adherence.

Hiroshi Nakagawa,1 Akio Hiura2 1Dentistry for Persons with Disability, Tokushima University Hospital, Tokushima, Japan; 2Department of Oral Histology, School of Dentistry, University of Tokushima, Tokushima, Japan Background: It has been demonstrated that N-ethyl-lidocaine (QX-314) can target the transient receptor protein vanilloid 1 (TRPV1) nociceptors when coadministered with capsaicin, resulting in a selective block of the nociceptors. Capsaicin is problematic in therapeutic use because it induces firing of nociceptors. The present study aimed to search for substitutes for capsaicin. We also examined the transportability of QX-314 into nociceptive neurons, through the pores of transient receptor potential ankyrin 1 (TRPA1), transient receptor potential melastatin-8 (TRPM8), and TRPV1. Methods: To investigate the effect on TRPA1, injections of a vehicle, allyl isothiocyanate (AITC), QX-314, or AITC/QX-314 were made into the hind paws of rats. The effects of menthol and capsaicin on the opening of TRPM8 and TRPV1 were also examined and compared with the potency of QX-314. To examine inhibition of the antinociceptive effect by capsaicin/QX-314, capsazepine (50 µg/mL; 10 µL) was injected 30 minutes prior to capsaicin/QX-314 (10 µL) injection. Thermal sensitivity was investigated by the Hargreaves method. 5(6)-carboxyfluorescein (FAM)-conjugated QX-314 was used as a tracer to examine how many and which kind of dorsal root ganglia accumulate this molecule. QX-314-FAM, capsaicin/QX-314-FAM, AITC/QX-314-FAM, and menthol/QX-314-FAM were injected into the paw. Two weeks after injections, dorsal root ganglia were removed and sectioned with a cryostat. Results: The capsaicin/QX-314 group induced longer withdrawal-response latency at 60 to 300 minutes after injection than the control. Both menthol only and menthol/QX-314 injections showed analgesia 10 to 60 minutes after injection. No significant difference was seen between the capsazepine/capsaicin/QX-314 group and the vehicle group. The fluorescence in small- and medium-sized neurons was conspicuous in only the dorsal root ganglia injected with capsaicin/QX-314-FAM. Conclusion: These results indicate that TRPA1 and TRPM8 are ineffective in the transport of QX-314 compared with TRPV1. Keywords: anesthetics, capsaicin, AITC, menthol, capsazepine, behavioral tests

Abstract Aim The available evidence for predicting length of stay in acute psychiatric hospitals includes demographics, diagnosis, and treatment variables. This study aimed to evaluate the association between neutrophil‐to‐lymphocyte ratio (NLR) and length of hospital stay in an acute psychiatric hospital. Methods A total of 116 patients who were admitted to an acute psychiatric ward at Urawa Neuropsychiatric Sanatorium (Saitama, Japan) from August 2022 to December 2022 were eligible for this study. Laboratory data of lymphocytes and neutrophils were assessed on the first day of admission and NLR was calculated based on the data. Participants were categorized into two groups, high NLR and low NLR, which were set as predictor variables, as well as using NLR as a continuous variable. Multiple linear regression was performed to determine the association between NLR and length of hospital stay, adjusting for confounding factors. Results A total of 90 participants were included in this study. The association of NLR as a continuous variable and length of hospital stay was not significant. When we categorized participants into high‐ and low‐NLR groups, the association was significant even after adjusting by covariates (p

Objective: Hypertension quality improvement programs reduce uncontrolled blood pressure (BP) but impact may differ by sex and age. Methods: This study examined uncontrolled BP, defined as a BP ≥ 140/90 mmHg, and therapeutic inertia, defined as absence of medication initiation or escalation during visits with uncontrolled BP, by sex and by age group (19–40, 41–65, 66–75, and 76+ years) during a 12 month follow-up period among 21, 861 patients with hypertension and ≥ two visits in primary care clinics enrolled in the American Medical Association (AMA) Measure Accurately, Act Rapidly, and Partner with Patients (MAP) BP hypertension quality improvement program. Results: The mean age was 64.8 years (standard deviation [SD 12.8]) and ranged from 19 to 87 years; 53.6% were female. In age groups 19–40, 41–65, 66–75, 76–87 years, uncontrolled BP at the first clinic visit was present in 51.5%, 42.5%, 37.5% and 36.6% of males, respectively, and in 40.0%, 38.0%, 36.0% and 39.6% of females, respectively. Based on vital signs at the first vs. last clinic visit, the proportion of patients with uncontrolled BP in age groups 19–40, 41–65, 66–75 years declined by 19.4%, 13.5%, 10.1% and 8.7% in males, respectively, and 14.4%, 12.5%, 9.3%, and 8.4%, among females, respectively. Therapeutic inertia ranged from 66.5% and 75.9% of clinic visits among males and females age 19–40 years, to 85.6% and 84.9% of clinic visits among males and females age 76–87 years, respectively. The proportion of clinic visits with therapeutic inertia was lower among males vs. females across all age groups until age 76–87 years. Conclusion: A quality improvement program improves BP control but declines in uncontrolled BP are larger and therapeutic inertia is lower for younger vs. older age groups and for males vs. females. More interventions are needed to reduce sex and age disparities in hypertension management.

Several factors related to liana abundance have been shown at broad scales, however, the information on factors affecting liana distribution in temperate zones is limited. Climbing types of lianas appear to be associated with interspecific variations of lianas and may be related to the broad-scale distribution and functions of lianas. We aimed to assess the environmental factors related to the abundance of all lianas and those of each climbing type from subtropical to subboreal forests in the Japanese archipelago to better understand the geographical gradient of the liana community.We established six 400 m2 subplots within each of 19 forest plots and recorded the species, stem diameter, and climbing types of lianas with stem diameters ≥ 1 cm. We used generalised linear mixed effects models and model selection based on Akaike's information criterion to examine the effects of climate, soil, and forest structural attributes on liana stem density and basal area.Liana abundance varied substantially among the 19 plots and some forests were characterized by abundant lianas in temperate zones. Twining and root climbers were the major climbing types. Mean annual temperature positively affected the stem density of twining climbers and negatively affected the basal area of root climbers. Maximum snow depth positively affected the stem density of root climbers and negatively affected the basal area of twining climbers. Carbon:nitrogen ratio and dry mass of the soil organic layer had negative effects on the abundance of twining climbers and stem density of both climbers, respectively. Tree basal area positively affected the basal area of root climbers.This study demonstrated the effects of environmental factors, including unique factors such as snow accumulation, on liana distribution at a broad scale from the subtropical to the subboreal zone. Furthermore, the difference between climbing types in distribution may contribute to the gradient of forest ecosystem functions along the environmental factors.

The link between forest productivity, species diversity and climate remains contentious. Here, Kohyama et al. examine stand productivity and tree diversity in old-growth forests from Japan to Indonesia, showing that warmer sites are more productive, largely due to small-biomass species.

Forests are major carbon sinks, but tree species composition and forest biomass have changed significantly under climate change. However, the extent to which forests have changed with climate change is unclear due to a lack of information before the recent climate change. In this study, we used forest inventory and environmental data (480 plots, 467 ha in total) from 1929 to 1938 in northern mixed forests in Japan (1) to estimate the biomass of the forest at that time, (2) to determine the environmental factors (temperature, precipitation, topographic wetness index, solar radiation, geology) affecting the AGB and species-specific biomass and (3) to estimate the relationship between AGB and diversity, structural equation models were used to determine whether the relationships are significant. The results showed that the average AGB of the forest was 61±22.4 (MgC/ha), which was not much higher than that of the present forest after human disturbances. Regarding species-specific biomass, biomass for subboreal conifers tended to increase in areas with less precipitation, and biomass for cool temperate deciduous broadleaved trees tended to increase in areas with more precipitation. Environmental factors indirectly affected AGB via forest structural factors, and the relationship between diversity and AGB was insignificant. This study revealed the feature of the forest ecosystem before recent climate change, and showed the potential for a detailed understanding of the effects of environmental factors related to biomass by analyzing species-specific response.

The temperature dependence of the optical properties of In0.4Ga0.6As0.98N0.02 quantum dots (QDs) was investigated using continuous-wave and time-resolved photoluminescence (PL). Significant increases in the PL peak energy and the PL linewidth were observed at temperatures above 200 K, which reflected the high luminescence efficiency of ground and excited states at high temperatures. The PL decay times of the ground state were almost constant between 200 and 300 K at 200–220 ps, which were significantly longer than that of 38 ps for the In0.4Ga0.6As QDs at 300 K. The temperature independence of the PL decay time represents significant suppression of the thermal escape and the thermal excitation of electrons because the electron ground-state localization energy is much larger than the thermal energy. The PL intensity of the In0.4Ga0.6As0.98N0.02 QDs was seven times stronger than that of the In0.4Ga0.6As QDs at 300 K, and this tendency was maintained up to 400 K with a PL intensity one order of magnitude stronger. These findings demonstrate that lowering the QD conduction band by nitrogen incorporation is an effective approach for achieving strong QD luminescence above room temperature. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction Poor glycemic control is known to be associated with severe infection development. This retrospective observational study examined whether glycemic control before coronavirus disease 2019 (COVID‐19) onset contributes to progression from non‐severe to severe COVID‐19. Materials and Methods Glycated hemoglobin (HbA1c) was measured on hospital admission in 415 patients with non‐severe COVID‐19. The outcome was determined from time of hospital admission to severe progression, based on clinical practice guidelines for COVID‐19 in Japan. Results The median value for HbA1c on admission was 6.1%, with diabetes present in 138 patients (33.3%). Among the total cohort, 93 (22.4%) progressed to severe COVID‐19 with a median (interquartile range) time of 4 days (3–7 days), whereas 322 (77.6%) were discharged after 13 days (10–17 days). A multivariable Cox proportional hazards regression model showed that HbA1c level on admission was independently associated with progression to severe COVID‐19 (hazard ratio for 1% increase 1.237, 95% confidence interval 1.037–1.475; P = 0.018), with findings consistent among several sensitivity analyses. In subgroup analyses, such an association was significant in patients with diabetes, as well as older age, current smoking habit, lower estimated glomerular filtration rate, higher C‐reactive protein level, moderate II COVID‐19, dyslipidemia and chronic respiratory disease, with no remarkable inconsistency among the subgroups. Finally, higher HbA1c level (≥7%) was more strongly associated with severe COVID‐19 progression than diabetes. Conclusions The results suggest that poor glycemic control before COVID‐19 onset contributes to progression from non‐severe to severe COVID‐19, even in patients with severe COVID‐19 risk factors regardless of the presence of diabetes.

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) 3He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP 3He MRI measuring pAO2, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm2/s) correlated with emphysema and heterogeneity in pAO2 measurements. Strong correlations were found between the heterogeneity of global pAO2 as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic pAO2 values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between pAO2 SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas pAO2 heterogeneity and the fraction of non-physiological pAO2 results increase in mild to moderate COPD. Measurements of pAO2 are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation.

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the ‘Hamburg Declaration’. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the ‘Global Alliance for the Promotion of Physical Activity’ to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The ‘Hamburg Declaration’ calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.

Purpose: The present study used near-infrared spectroscopy to investigate the relationships between cerebral oxygen metabolism and perfusion in the prefrontal cortex (PFC) during exercises of different intensities.Methods: A total of 12 recreationally active men (age 24 ± 6 years) were enrolled. They performed 17 min of low-intensity exercise (ExL), followed by 3 min of moderate-intensity exercise (ExM) at constant loads. Exercise intensities for ExL and ExM corresponded to 30% and 45% of the participants’ heart rate reserve, respectively. Cardiovascular and respiratory parameters were measured. We used near-infrared time-resolved spectroscopy (TRS) to measure the cerebral hemoglobin oxygen saturation (ScO2) and total hemoglobin concentration ([HbT]), which can indicate the cerebral blood volume (CBV). As the cerebral metabolic rate for oxygen (CMRO2) is calculated using cerebral blood flow (CBF) and ScO2, we assumed a constant power law relationship between CBF and CBV based on investigations by positron emission tomography (PET). We estimated the relative changes in CMRO2 (rCMRO2) and CBV (rCBV) from the baseline. During ExL and ExM, the rate of perceived exertion was monitored, and alterations in the subjects’ mood induced by exercise were evaluated using the Profile of Moods Scale-Brief.Results: Three minutes after exercise initiation, ScO2 decreased and rCMRO2 surpassed rCBV in the left PFC. When ExL changed to ExM, cardiovascular variables and the sense of effort increased concomitantly with an increase in [HbT] but not in ScO2, and the relationship between rCMRO2 and rCBV was dissociated in both sides of the PFC. Immediately after ExM, [HbT], and ScO2 increased, and the disassociation between rCMRO2 and rCBV was prominent in both sides of the PFC. While blood pressure decreased and a negative mood state was less prominent following ExM compared with that at rest, ScO2 decreased 15 min after exercise and rCMRO2 surpassed rCBV in the left PFC.Conclusion: Dissociated coupling between cerebral oxidative metabolism and perfusion in the PFC was consistent with the effort required for increased exercise intensity and associated with post-exercise hypotension and altered mood status after exercise. Our result demonstrates the first preliminary results dealing with the coupling between cerebral oxidative metabolism and perfusion in the PFC using TRS.