Separable amygdala activation patterns in the evaluations of robots.

Given the increasing presence of robots in everyday environments and the significant challenge posed by social interactions with robots, it is crucial to gain a deeper understanding into the social evaluations of robots. One potentially effective approach to comprehend the fundamental processes underlying controlled and automatic evaluations of robots is to probe brain response to different perception levels of robot-related stimuli. Here, we investigate controlled and automatic evaluations of robots based on brain responses during viewing of suprathreshold (duration: 200 ms) and subthreshold (duration: 17 ms) humanoid robot stimuli. Our behavioral analysis revealed that despite participants' self-reported positive attitudes, they held negative implicit attitudes toward humanoid robots. Neuroimaging analysis indicated that subthreshold presentation of humanoid robot stimuli elicited significant activation in the left amygdala, which was associated with negative implicit attitudes. Conversely, no significant left amygdala activation was observed during suprathreshold presentation. Following successful attenuation of negative attitudes, the left amygdala response to subthreshold presentation of humanoid robot stimuli decreased, and this decrease correlated positively with the reduction in negative attitudes. These findings provide evidence for separable patterns of amygdala activation between controlled and automatic processing of robots, suggesting that controlled evaluations may influence automatic evaluations of robots.

Higher emotional synchronization is modulated by relationship quality in romantic relationships and not in close friendships.

Emotions are fundamental to social interaction and deeply intertwined with interpersonal dynamics, especially in romantic relationships. Although the neural basis of interaction processes in romance has been widely explored, the underlying emotions and the connection between relationship quality and neural synchronization remain less understood. Our study employed EEG hyperscanning during a non-interactive video-watching paradigm to compare the emotional coordination between romantic couples and close friends. Couples showed significantly greater behavioral and prefrontal alpha synchronization than friends. Notably, couples with low relationship quality required heightened neural synchronization to maintain robust behavioral synchronization. Further support vector machine analysis underscores the crucial role of prefrontal activity in differentiating couples from friends. In summary, our research addresses gaps concerning how intrinsic emotions linked to relationship quality influence neural and behavioral synchronization by investigating a natural non-interactive context, thereby advancing our understanding of the neural mechanisms underlying emotional coordination in romantic relationships.

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

PURPOSE: This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. METHODS: The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. RESULTS: In this study, 2236 patients with mTNBC (median age 66.0 years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2 months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. CONCLUSION: This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Prevalence and clinical characteristics of people with HIV with limited treatment options in Japan: A Japanese claims data analysis.

INTRODUCTION: Long-term medication leads some people with HIV (PWH) to limited treatment options (LTO) due to multiple factors. The present study investigated the prevalence of PWH with LTO in Japan and their clinical characteristics, persistence, and adherence. METHODS: PWH who received antiretroviral therapy (ART) between 2017 and 2022 were identified in the Medical Data Vision (MDV) Japanese claims database. PWH with LTO were defined as: 1) receiving regimens indicative for LTO or 2) having a complex treatment history (≥4 different core agents, ≥11 ART agents). Prevalence by calendar year, clinical characteristics, persistence, and adherence measured by the proportion of days covered (PDC) of ART were investigated. RESULTS: A total of 5740 PWH were included, and 207 (3.6 %) were identified as LTO. Mean (SD) age was 50.3 (11.8) years, 148 (71.5 %) had evidence of AIDS-defining condition, and 25 (12.1 %) had hemophilia. The prevalence of PWH with LTO increased from 2.58 % in 2017 to 3.55 % in 2022. Persistence at 1 year was estimated as 70.3 % and mean PDC through 1 year was 96.7 %. CONCLUSION: Between the years 2017-2022, 3.6 % (approximately 200) Japanese PWH were identified as having LTO. The results of this analysis found clinical characteristics of PWH with LTO as older age and higher percentages with an AIDS-defining condition and hemophilia than the general HIV population. Low persistence indicates that treatment optimization is required in this population. These results will help health care providers to understand the clinical characteristics of PWH with LTO and may contribute to the establishment of appropriate treatment strategies.

Hysteresis effects of different levels of storm flooding on susceptible enteric infectious diseases in a central city of China.

BACKGROUND: Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. METHODS: Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. RESULTS: There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71-4.76) and 8.16 (95% CI: 2.93-22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40-2.35) and 3.31 (95% CI: 1.97-5.55) after 5 days of general flooding and heavy flooding, respectively. CONCLUSIONS: Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

Enhanced amyloid-ß generation by γ-secretase complex in DRM microdomains with reduced cholesterol levels.

A neuropathologic hallmark of Alzheimer's disease (AD) is the presence of senile plaques that contain neurotoxic amyloid-ß protein (Aß) species, which are generated by the cleavage of amyloid ß-protein precursor by secretases such as the γ-secretase complex, preferentially located in detergent-resistant membrane (DRM) regions and comprising endoproteolysed amino- and carboxy-terminal fragments of presenilin, nicastrin, anterior pharynx defective 1 and presenilin enhancer 2. Whereas some of familial AD patients harbor causative PSEN mutations that lead to more generation of neurotoxic Aß42, the contribution of Aß generation to sporadic/late-onset AD remains unclear. We found that the carboxy-terminal fragment of presenilin 1 was redistributed from DRM regions to detergent-soluble membrane (non-DRM) regions in brain tissue samples from individuals with sporadic AD. DRM fractions from AD brain sample had the ability to generate significantly more Aß and had a lower cholesterol content than DRM fractions from non-demented control subjects. We further demonstrated that lowering the cholesterol content of DRM regions from cultured cells contributed to the redistribution of γ-secretase components and Aß production. Taken together, the present analyses suggest that the lowered cholesterol content in DRM regions may be a cause of sporadic/late-onset AD by enhancing overall Aß generation.

Real-world treatment patterns and clinical outcomes of Japanese patients with non-muscle invasive bladder cancer receiving intravesical bacillus Calmette-Guérin treatment.

OBJECTIVES: To investigate current patterns and outcomes of intravesical bacillus Calmette-Guérin treatment in Japanese patients with bladder cancer, including the proportion of patients completing induction therapy, and time to subsequent treatments. METHODS: This retrospective cohort study utilized administrative claims data from the Medical Data Vision Co., Ltd. database to identify patients with a diagnosis of bladder cancer who had received ≥1 prescription of intravesical bacillus Calmette-Guérin between April 2008 and September 2015, and had ≥1 database record dated ≥12 weeks after the initial bacillus Calmette-Guérin dose. Patients were followed until September 2018, the last date of available data, or in-hospital death. Patients receiving six doses of bacillus Calmette-Guérin at intervals of <21 days were considered to have completed induction according to guidelines. Time from initial bacillus Calmette-Guérin dose to subsequent bladder cancer treatment after the end of treatment was defined as the recurrence-free duration. RESULTS: Of 6140 patients identified (median age 73.0 years; 83.4% males), 4588 (74.7%) completed induction and 1552 (25.3%) did not. Median recurrence-free duration was 64.4, 77.7, and 31.6 months in the overall, complete-induction and incomplete-induction cohorts, respectively. Corresponding 3-year recurrence-free rate was 56.3%, 59.0%, and 48.2% in these groups. The rate of cystectomy was approximately 6% at 5 years in all cohorts. CONCLUSIONS: Approximately 75% of Japanese patients who undergo intravesical bacillus Calmette-Guérin treatment receive a guideline-compliant induction regimen, but outcomes were not satisfactory, highlighting the need for more effective treatments for non-muscle invasive bladder cancer.

Regional differences in the incidence of asthma exacerbations in Japan: A heat map analysis of healthcare insurance claims data.

BACKGROUND: In Japan, regional differences in asthma mortality have been reported; however, regional differences in asthma exacerbations have not been studied extensively. Therefore, using a health insurance claims database, we investigated the regional differences in the incidence of asthma exacerbations in Japan. METHODS: This study used data from Medi-Scope (Japan Medical Information Research Institute Inc., Japan)-a nationwide health insurance claims database. Patients with asthma at the index date (the latest date of an asthma-related prescription with an asthma diagnosis before October 1, 2018) were included in the analysis. The pre-index period was defined as 1 year before the index date, and the follow-up period as 1 year after the index date. The incidence of asthma exacerbation events was analyzed for each region. RESULTS: The primary analysis population comprised 24,883 patients who were continuously prescribed ICS or ICS/LABA at least four times during the pre-index period. The incidence rate of asthma exacerbations with hospitalization was the highest in Chugoku (2.95/100 person-years [95% CI, 1.97-4.43]) and the lowest in Kanto (1.52/100 person-years [95% CI, 1.26-1.83]). The incidence rate of asthma exacerbations for the composite outcome of hospitalization, injectable corticosteroid prescription, and oral corticosteroid burst was the highest in Fukui (105.00/100 person-years [95% CI, 64.53-170.85]) and the lowest in Nagasaki (15.69/100 person-years [95% CI, 10.84-22.72]). CONCLUSIONS: Regional differences in the incidence of asthma exacerbations as well as their treatments were observed in Japan.

Molecular Basis for Chemical Evolution of Flavones to Flavonols and Anthocyanins in Land Plants.

During the course of evolution of land plants, different classes of flavonoids, including flavonols and anthocyanins, sequentially emerged, facilitating adaptation to the harsh terrestrial environment. Flavanone 3ß-hydroxylase (F3H), an enzyme functioning in flavonol and anthocyanin biosynthesis and a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) family, catalyzes the hydroxylation of (2S)-flavanones to dihydroflavonols, but its origin and evolution remain elusive. Here, we demonstrate that functional flavone synthase Is (FNS Is) are widely distributed in the primitive land plants liverworts and evolutionarily connected to seed plant F3Hs. We identified and characterized a set of 2-ODD enzymes from several liverwort species and plants in various evolutionary clades of the plant kingdom. The bifunctional enzyme FNS I/F2H emerged in liverworts, and FNS I/F3H evolved in Physcomitrium (Physcomitrella) patens and Selaginella moellendorffii, suggesting that they represent the functional transition forms between canonical FNS Is and F3Hs. The functional transition from FNS Is to F3Hs provides a molecular basis for the chemical evolution of flavones to flavonols and anthocyanins, which contributes to the acquisition of a broader spectrum of flavonoids in seed plants and facilitates their adaptation to the terrestrial ecosystem.

Mobile HIV Testing Through Social Networking Platforms: Comparative Study.

BACKGROUND: Improving HIV screening in key populations is a crucial strategy to achieve the goal of eliminating AIDS in 2030. Social networking platforms can be used to recruit high risk-taking men who have sex with men (MSM) to promote the delivery of voluntary counseling and testing (VCT) as mobile HIV testing. Therefore, client recruitment and availability of mobile HIV testing through social networking platforms requires further evaluation. OBJECTIVE: The aim of this study is to compare the effects of targeting high risk-taking MSM and HIV case finding between two mobile HIV testing recruitment approaches: through the traditional website-based approach and through social networking platforms. METHODS: A comparative study design and propensity score matching was applied. The traditional VCT model, that is, the control group, recruited MSM through a website, and a trained research assistant visited the walk-in testing station at a gay village on Friday and Saturday nights. The social networking VCT model, the experimental group, recruited MSM from social networking platforms by periodically reloading into and conducting web-based discussions on dating apps and Facebook. The participants then referred to others in their social networks via a popular messenger app in Taiwan. The test was conducted at a designated time and place during weekdays by a trained research assistant. Across both modes of contact, before the mobile HIV testing, participants needed to provide demographic characteristics and respond to a questionnaire about HIV risk-taking behaviors. RESULTS: We recruited 831 MSM over 6 months, with a completion rate of 8.56% (616/7200) in the traditional VCT model and 20.71% (215/1038) in the social networking VCT model. After propensity score matching, there were 215 MSM in each group (mean age 29.97, SD 7.61 years). The social networking model was more likely to reach MSM with HIV risk-taking behaviors, that is, those seeking sexual activity through social media, having multiple sexual partners and unprotected anal intercourse, having experience of recreational drug use, and never having or not regularly having an HIV test, compared with the traditional model. HIV positive rates (incidence rate ratio 3.40, 95% CI 1.089-10.584; P=.03) and clinic referral rates (incidence rate ratio 0.03, 95% CI 0.001-0.585; P=.006) were significantly higher among those in the social networking VCT model than in the traditional VCT model. CONCLUSIONS: Through effective recruitment strategies on social networking platforms, the social networking VCT mode can be smoothly promoted, as compared with the traditional VCT model, to target high risk-taking MSM and increase testing outcomes.

Identification and evolutionary analysis of chalcone isomerase-fold proteins in ferns.

The distribution of type I and II chalcone isomerases (CHIs) in plants is highly family specific. We have previously reported that ancient land plants, such as the liverworts and Selaginella moellendorffii, harbor type II CHIs. To better understand the function and evolution of CHI-fold proteins, transcriptomic data obtained from 52 pteridophyte species were subjected to sequence alignment and phylogenetic analysis. The residues determining type I/II CHI identity in the pteridophyte CHIs were identical to those of type I CHIs. The enzymatic characterization of a sample of 24 CHIs, representing all the key pteridophyte lineages, demonstrated that 19 of them were type I enzymes and that five exhibited some type II activity due to an amino acid mutation. Two pteridophyte chalcone synthases (CHSs) were also characterized, and a type IV CHI (CHIL) was demonstrated to interact physically with CHSs and CHI, and to increase CHS activity by decreasing derailment products, thus enhancing flavonoid production. These findings suggest that the emergence of type I CHIs may have coincided with the divergence of the pteridophytes. This study deepens our understanding of the molecular mechanism of CHIL as an enhancer in the flavonoid biosynthesis pathway.

Effects of mobile health on HIV risk reduction for men who have sex with men.

Mobile health (M-Health) has become a novel method for HIV prevention and the effects need to be promoted. The study purpose was to exam how a smartphone application (app) reduces HIV risky behaviour in men who have sex with men (MSM). The Safe Behaviour and Screening (SBS) app was developed, and included five features: record, output, and resources connection; information provision; testing services; interaction; and online statistics. A random assignment was used. The experimental group used the SBS app for six months. The control group did not use any intervention. There were 130 participants in the experimental group, and 135 in the control group. The average age of all subjects was 27.38 (SD = 5.56). Compared to the control group, the experimental group had significantly higher mean score of safe behaviour knowledge, motivation, and skills; percentage of condom use during anal intercourse; frequency of searching for testing resources and getting HIV and syphilis tests. The frequency of anal intercourse and recreational drug usage were significantly lower in the experimental group. The SBS app could decrease the HIV risky behaviour among MSM and be applied to HIV prevention and nursing intervention.

Effects of exercise interventions on social and cognitive functioning of men with prostate cancer: a meta-analysis.

PURPOSE: Exercise is beneficial for prostate cancer patients' physical functioning; however, effects on social and cognitive functioning are inconsistent. This meta-analysis of exercise interventions for prostate cancer patients had two aims: the primary aim was to evaluate the effects of exercise interventions on social functioning; the secondary aim was to consider additional outcomes of cognitive functioning as well as adverse events. METHODS: Electronic databases (Embase, MEDLINE, PubMed, PsycINFO, and the Chinese database Airti Library) were searched for relevant papers (1987-2019), which included hand searching. After careful inspection, 10 relevant randomized controlled trials were analyzed using Comprehensive Meta-Analysis software; pooled means determined social and cognitive functioning. RESULTS: Meta-analysis of summary scores (fixed-effects model) showed an overall beneficial effect of exercise on social functioning (Hedges' g = 0.35, 95% CI [0.193, 0.515], p < 0.001) and cognitive functioning (Hedges' g = 0.35, 95% CI [0.123, 0.575], p < 0.01) in men with prostate cancer when compared to controls. Intervention durations of 12-16 and 24-48 weeks that provided supervised aerobic exercise combined with resistance exercise sessions had a small to medium effect on social functioning compared to controls. One exercise group experienced one serious, but non-fatal, adverse event due to a higher exercise intensity (50-75% VO2max). DISCUSSION AND RECOMMENDATIONS: To the best of our knowledge, this is the first meta-analysis to examine the effects of exercise interventions on cognitive functioning among prostate cancer patients. We suggest further research be conducted to confirm these findings.

Factors affecting mammography screening behaviour among rural Vietnamese women.

OBJECTIVES: To identify factors associated with mammography screening behaviour and its predictors among rural Vietnamese women. METHOD: A predictive correlational study involving 120 women aged ≥ 40 years was conducted in the suburbs of Hanoi, Vietnam, in July 2018 by using Breast Cancer Awareness Measurement and the Champion Health Beliefs Model Scale. Mammography screening behaviour was assessed by asking participants about their previous mammography experience. RESULTS: Only 16.7% of participants had undergone mammography screening. High education levels, high monthly family income, having family members or friends with breast cancer, and receiving physicians' recommendations increased the likelihood of participants screening for breast cancer. Mean scores on perceived susceptibility and perceived barriers differed significantly between participants who had and those who had not undergone screening (t = 4.31; p < .001; t = -5.05; p < .001, respectively). Perceived susceptibility and perceived barriers significantly increased the predictive power of the hierarchical logistic model (critical value = 6.16; [df = 2]; p = .046). Perceived barriers were the most significant predictors of screening behaviour (odds ratio 0.84; 95% CI, 0.71-0.99; p = .039). CONCLUSION: Efforts are necessary to increase mammography awareness in the community and promote screening rates in Vietnam.

Foot care knowledge, attitudes and practices among patients with diabetic foot and amputation in St. Kitts and Nevis.

About one-third of admissions to the surgical unit annually are diabetes foot infections in need of amputation In St. Kitts and Nevis. However, the risk factors related to diabetes foot and amputation remain unknown. This study investigated factors associated with diabetic foot and amputation (DFA). Retrospective case control study design, and purposive and quota sampling method was used to recruit the participants. Patients with and without DFA were interviewed at two main hospitals, several primary health centres, and a private doctor's office during July and August 2018. Self-development questionnaires were applied to assess patients' demographic, physical and behaviour, foot care knowledge, attitudes, and practices related to DFA. Chi-square, t-test, and multiple logistic regressions were used to analyse the data. A total of 210 patients were evaluated, 89 had DFA, while 121 did not, with a mean age of 61.10 (SD = 11.85). Participants' responses indicated good knowledge, favourable attitudes, and adequate practices related to foot care. The two items of the questionnaire, ways to maintain blood flow in the lower extremities and wash their feet daily, had significant lower score in DFA group. In multiple logistic regression, knowledge, attitudes, and practices related to foot care were not a significant predictor of DFA. Being male was a predictor of DFA than female (OR = 3.53; 95% CI = 1.65-7.57; P < .01). Participants who were currently unemployed were less likely to have DFA than those who were employed (OR = 0.38; 95% Cl = 0.17-0.86; P < .05). Comparing patients with the longest experience of diabetes mellitus (31 years or more) with those who had diabetes for the shortest period of time (between 1 and 10 years) was less likely to have DFA (OR = 0.38; 95% CI = 0.15-0.97; P = <.05). The combination of these independent variables could explain 29% of the variance in DFA. Based on these findings, strategies to prevent diabetic foot and amputation should focus on male and outdoor heavy worker, and longer duration of diabetes patients which are identified in this study.

Functional characterization of a liverworts bHLH transcription factor involved in the regulation of bisbibenzyls and flavonoids biosynthesis.

BACKGROUND: The basic helix-loop-helix (bHLH) transcription factors (TFs), as one of the largest families of TFs, play important roles in the regulation of many secondary metabolites including flavonoids. Their involvement in flavonoids synthesis is well established in vascular plants, but not as yet in the bryophytes. In liverworts, both bisbibenzyls and flavonoids are derived through the phenylpropanoids pathway and share several upstream enzymes. RESULTS: In this study, we cloned and characterized the function of PabHLH1, a bHLH family protein encoded by the liverworts species Plagiochasma appendiculatum. PabHLH1 is phylogenetically related to the IIIf subfamily bHLHs involved in flavonoids biosynthesis. A transient expression experiment showed that PabHLH1 is deposited in the nucleus and cytoplasm, while the yeast one hybrid assay showed that it has transactivational activity. When PabHLH1 was overexpressed in P. appendiculatum thallus, a positive correlation was established between the content of bibenzyls and flavonoids and the transcriptional abundance of corresponding genes involved in the biosynthesis pathway of these compounds. The heterologous expression of PabHLH1 in Arabidopsis thaliana resulted in the activation of flavonoids and anthocyanins synthesis, involving the up-regulation of structural genes acting both early and late in the flavonoids synthesis pathway. The transcription level of PabHLH1 in P. appendiculatum thallus responded positively to stress induced by either exposure to UV radiation or treatment with salicylic acid. CONCLUSION: PabHLH1 was involved in the regulation of the biosynthesis of flavonoids as well as bibenzyls in liverworts and stimulated the accumulation of the flavonols and anthocyanins in Arabidopsis.

Medication Adherence/Persistence and Demographics of Japanese Dyslipidemia Patients on Statin-Ezetimibe as a Separate Pill Combination Lipid-Lowering Therapy　- An Observational Pharmacy Claims Database Study.

BACKGROUND: This study aimed to identify potential predictors of medication adherence and persistence with statin-ezetimibe combinational lipid-lowering therapy (LLT) as a separate pill combination in a real-world setting in Japan.Methods and Results:Patients newly switched to statin-ezetimibe combinational LLT from statin monotherapy were identified within a Japanese national pharmacy claims database during January 2015 to April 2018. Adherence and persistence were measured by the proportion of days covered (PDC), time to treatment discontinuation and persistence rate at 1 year. A stepwise multivariate logistic regression model and Cox proportional hazards regression model were used to explore potential predictors associated with adherence and persistence, respectively. Among 6,921 patients, 71.9% were adherent (PDC ≥80%), and 83.6% were persistent at 1 year after initiation. Patients aged ≤54 years and ≥75 years were prone to be more non-adherent. Secondary prevention was associated with better adherence and longer persistence. Concomitant use of medications for depression/anxiety was associated with shorter persistence, whereas use of antihypertensive drugs was associated with better adherence and persistence. CONCLUSIONS: Age, concomitant use of certain classes of medications (or the existence of these diseases) and secondary prevention were associated with adherence and persistence of statin-ezetimibe combinational LLT. Given that dyslipidemia is a chronic disease requiring life-long control, active interventions are required for patients with poor adherence and persistence.

Cytoplasmic fragment of Alcadein α generated by regulated intramembrane proteolysis enhances amyloid ß-protein precursor (APP) transport into the late secretory pathway and facilitates APP cleavage.

The neural type I membrane protein Alcadein α (Alcα), is primarily cleaved by amyloid ß-protein precursor (APP) α-secretase to generate a membrane-associated carboxyl-terminal fragment (Alcα CTF), which is further cleaved by γ-secretase to secrete p3-Alcα peptides and generate an intracellular cytoplasmic domain fragment (Alcα ICD) in the late secretory pathway. By association with the neural adaptor protein X11L (X11-like), Alcα and APP form a ternary complex that suppresses the cleavage of both Alcα and APP by regulating the transport of these membrane proteins into the late secretory pathway where secretases are active. However, it has not been revealed how Alcα and APP are directed from the ternary complex formed largely in the Golgi into the late secretory pathway to reach a nerve terminus. Using a novel transgenic mouse line expressing excess amounts of human Alcα CTF (hAlcα CTF) in neurons, we found that expression of hAlcα CTF induced excess production of hAlcα ICD, which facilitated APP transport into the nerve terminus and enhanced APP metabolism, including Aß generation. In vitro cell studies also demonstrated that excess expression of Alcα ICD released both APP and Alcα from the ternary complex. These results indicate that regulated intramembrane proteolysis of Alcα by γ-secretase regulates APP trafficking and the production of Aß in vivo.

The effects of early multiple-time PN counseling on newly HIV-diagnosed men who have sex with men in Taiwan.

Partner notification (PN) is an important method for controlling the AIDS epidemic worldwide. Here, we looked into the differences between two PN counseling modes for HIV (+) men who have sex with men in Taiwan. Using random assignment, we placed 42 of the 84 subjects into the experimental group where they received two sessions of PN counseling, while the control group (42) received only one session. All 84 subjects were single males with an average age of 28.06. The mean number of successful notified partner was 5.38 (SD = 3.44) in the experimental which was statistically significantly higher than 2.81 (SD = 1.62) in the control group (ß = 0.650, p = 0.000). The notification success rate was 77.13 % in the experimental and 74.21 % in the control group (IRR 1.039, 95 % CI 0.83-1.30). In the experimental and control group, the average number of the partners accepted an HIV test was 1.86 (SD = 1.58) and 0.79 (SD = 0.66) (ß = 0.601, p = 0.000), and 39.74 and 27.27 % of the tested partners were HIV positive (IRR 1.457, 95 % CI 0.69-3.06). The study results may be used to improve the policies and practices for PN and contact follow-up.

Relationship between adherence to bictegravir/emtricitabine/tenofovir alafenamide fumarate and clinical outcomes in people with HIV in Japan: a claims database analysis.

A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.