Acute Vigorous Exercise Decreases Subsequent Non-Exercise Physical Activity and Body Temperature Linked to Weight Gain.

PURPOSE: Exercise benefits the body and mind, but its weight loss effect is less than generally expected. Although this phenomenon is likely due to an exercise intensity-dependent decrease in non-exercise physical activity (NEPA), resulting in a decrease in non-exercise activity thermogenesis, the underlying mechanisms and effects of exercise intensity remain unknown. Here we show that acute vigorous exercise decreases subsequent NEPA and body temperature (BT) in association with body weight gain. METHODS: Adult male C57BL/6 J mice were categorized into three groups: sedentary, moderate exercise, and vigorous exercise, with exercise groups undergoing a 30 min treadmill session. Using an intraperitoneally implanted activity monitor, NEPA and BT were monitored for two days before and three days after exercise. The daily synchrony between NEPA and BT was evaluated using a cross-correlation function. Plasma corticosterone was also detected 6 and 24 h after exercise. RESULTS: Notably, Only the vigorous exercise group exhibited a decline in both NEPA and BT, resulting in body weight gain the following day, despite no observed changes in food intake. Furthermore, vigorous exercise induces a distinct delay in the daily dynamics of NEPA compared to BT. A positive correlation was observed between plasma corticosterone levels and changes in NEPA levels before and after exercise across all exercise groups. CONCLUSIONS: Our findings provide evidence for vigorous exercise-specific reduction in subsequent NEPA, BT, and their synchrony linked to weight gain, likely due to the disturbed circadian rhythm of corticosterone. This is an initial investigation redefining the significance of exercise intensity in beneficial effects beyond the energy expenditure of the exercise itself.

Experiences in COVID-19 clinical management and health-care pathways in the Western Pacific.

The coronavirus disease (COVID-19) pandemic has transformed clinical practice and health systems. This paper provides an overview of COVID-19 clinical management and health-care pathway challenges that the World Health Organization and its Member States in the Western Pacific Region have faced. The experiences and lessons identified can help countries to better prepare for future pandemics.

Enlarged housing space and increased spatial complexity enhance hippocampal neurogenesis but do not increase physical activity in mice.

Introduction: Environmental enrichment (EE) improves various health outcomes, such as hippocampal neurogenesis, in rodents, which is thought to be caused, in part, by increased physical activity. However, the specific effect of each enrichment component, such as enlarged housing spaces and increased spatial complexity with a variety of objects, on physical activity remains unclear because of methodological limitations in measuring physical activity. We aimed to examine whether enlarged housing spaces and increased spatial complexity increase physical activity in mice using a body-implantable actimeter. Methods: Adult male C57BL/6J mice were assigned to either standard housing or EE groups. The housing environment in the EE mice was gradually enriched by enlarging the housing space and the placement of a variety of objects. Physical activity was measured using a body-implanted actimeter. Hippocampal neurogenesis was immunohistochemically examined. Results: Enlarged housing spaces and the placement of a variety of objects did not increase physical activity in mice. In contrast, hippocampal neurogenesis was enhanced in the EE mice, suggesting that environmental interventions successfully provided enriched housing conditions for these mice. Conclusions: These results indicate that enlarged housing spaces and increased spatial complexity do not increase physical activity in mice. Furthermore, we found that EE enhanced hippocampal neurogenesis without increasing activity volume. Besides the current understanding that increasing the amount of physical activity is key to improving hippocampal function, our result suggests that the environment in which physical activity takes place is also a crucial contextual factor in determining the impact of physical activity on hippocampal function.

Maintaining health-system functionality in response to the surge of COVID-19 cases due to the Omicron variant, Japan.

Problem: The Omicron variant of severe acute respiratory syndrome coronavirus 2 caused the largest surge of coronavirus disease (COVID-19) cases in Japan starting in the summer of 2022. We describe the mechanisms introduced to provide appropriate health care to all Omicron cases, provide appropriate health care to all non-COVID-19 patients, and protect health-care workers (HCWs) while providing necessary health services. Optimization of care for elderly patients was particularly important. Context: Japan is home to 125 million people, of whom 28.6% are 65 years or older. Between January and June 2022, the country experienced 4.3 times more COVID-19 cases than in the previous 2 years (7.3 million vs 1.7 million). Action: To adjust care pathways, inpatient treatment capacity was increased, a home-based care system was established, and an on-site treatment scheme at long-term care facilities was started. Among essential health services, disruption of emergency care became most noticeable. Administrative and financial support was provided to hospitals with emergency departments to maintain emergency medical services. To protect HCWs while maintaining hospital services, flexible exemptions were introduced to enable those who became close contacts to return to work, and broadly targeted contact tracing and testing in case of nosocomial outbreaks were all helpful. Outcome: As a result of the adjustments made to inpatient capacity and patient flow, bed occupancy for COVID-19 patients decreased, mostly because many patients were cared for at home or in temporary-care facilities. Discussion: From this study, we extracted two essential lessons to aid in current and future health emergencies: how to balance the provision of acute medical care for elderly patients and maintain their well-being; and how to maintain essential health services.

Exercise type influences the effect of an acute bout of exercise on hippocampal neuronal activation in mice.

The effects of exercise on the hippocampus depend on exercise conditions. Exercise intensity is thought to be a dominant factor that influences the effects of exercise on the hippocampus; however, it is uncertain whether the type of exercise influences its effectiveness. This study investigated whether the effect of an acute bout of exercise on hippocampal neuronal activation differs between two different types of exercise: treadmill and rotarod exercise. The intensities of both exercises were matched at just below the lactate threshold (LT), based on blood lactate concentration. Immunohistochemical examination of c-Fos, a marker of neuronal activation, revealed that treadmill exercise at 15 m/min (T15) significantly increased c-Fos expression in all subfields of the hippocampus (dentate gyrus DG, CA1, CA3), but rotarod exercise at 30 rpm (R30) did not, as compared with the respective control groups. These results demonstrate that moderate treadmill exercise more efficiently evokes hippocampal neuronal activation than does intensity-matched rotarod exercise. This suggests that exercise type is another important factor affecting the effects of exercise on the hippocampus.

High prevalence of pre-treatment HIV drug resistance in Papua New Guinea: findings from the first nationally representative pre-treatment HIV drug resistance study.

BACKGROUND: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. METHODS: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. RESULTS: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8-24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6-23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6-17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1-56.4%). CONCLUSIONS: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.

Social isolation is a direct determinant of decreased home-cage activity in mice: A within-subjects study using a body-implantable actimeter.

NEW FINDINGS: What is the central question of this study? It is generally recognized that social isolation is associated with physical inactivity, but is social isolation a direct determinant of decreased physical activity? What is the main finding and its importance? We conducted a within-subjects experiment with the aid of a body-implantable actimeter. Our results clearly demonstrated that social isolation decreased home-cage activity in mice. This might have resulted from increased immobility and decreased vigorous activity, suggesting that avoidance of social isolation is important to prevention of physical inactivity. ABSTRACT: An inactive lifestyle can have a negative impact on physiological and mental health. Social isolation is associated with physical inactivity; however, it remains uncertain whether social isolation is a direct determinant of decreased physical activity. Hence, we assessed whether social isolation decreases home-cage activity using a within-subjects design and examined the effects of social isolation on hippocampal neurogenesis in mice. This study used a body-implantable actimeter called nanotag, which enabled us to measure home-cage activity despite housing the mice in groups. Initially, we examined the influence of the intraperitoneal implantation of nanotag on home-cage activity. Although nanotag implantation decreased home-cage activity temporarily, at 7 days postimplantation the activity recovered to the same level as that of control (non-implanted) mice, suggesting that implantation of nanotag does not have a negative influence on home-cage activity if mice undergo a 1 week recovery period after implantation. In the main experiment, after the 1 week baseline measurement performed with mice in group housing, the mice were placed in a group or in isolation. Home-cage activity was measured for an additional 4 weeks. Home-cage activity in isolated mice during the dark period decreased by 26% from pre-intervention to the last week of intervention. Furthermore, the reduction in the number of 5 min epochs during which the activity count exceeded 301 (an index of vigorous activity) was significantly larger for isolated mice. Contrary to expectations, social isolation did not impair hippocampal neurogenesis. Our results demonstrate that social isolation is a direct determinant of decreased physical activity, possibly because of reduced vigorous physical activity.

Long-term weight gain after initiating combination antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus.

OBJECTIVE: To investigate changes in weight following the initiation of antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus (PLWH). METHODS: This retrospective observational study evaluated adult treatment-naïve Asian PLWH who started antiretroviral therapy based on an integrase strand transfer inhibitor, a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor at the AIDS Clinical Centre, Tokyo between January 2005 and February 2019. Patients were followed-up until October 2019. Multi-variate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight was reported at 3-month intervals until censoring or for 5 years after treatment initiation. RESULTS: Five years after treatment initiation, average weight gain in PLWH who started on dolutegravir-, darunavir- and elvitegravir-based treatment was 5.3 kg, 4.1 kg and 4.6 kg, respectively, while those who started on raltegravir-, lopinavir- and atazanavir-based treatment gained an average of 1.9 kg, 2.1 kg and 2.3 kg, respectively. Average weight gain in PLWH who started treatment with the backbone drugs, tenofovir alafenamide, abacavir and tenofovir disproxil fumarateb was 4.1 kg, 3.0 kg and 3.0 kg, respectively, and those treated with dolutegravir plus tenofovir alafenamide/emtricitabine gained an average of 6.7 kg. CONCLUSIONS: Antiretroviral-therapy-associated weight gain continued to increase for 5 years following treatment initiation. A combination of dolutegravir and tenofovir alafenamide/emtricitabine was associated with the greatest weight gain.

Interaction between intensity and duration of acute exercise on neuronal activity associated with depression-related behavior in rats.

We examined the activities of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) during acute treadmill running at different speeds (control, low, high) and durations (15, 30, 60 min) in male Wistar rats using c-Fos/5-HT or CRF immunohistochemistry. We also performed elevated plus maze test (EPM) and forced swim test (FST) after acute treadmill running in rats. Acute treadmill running at low speed, regardless of exercise duration, significantly increased c-Fos expression in 5-HT neurons in the DRN compared with controls, whereas high-speed running significantly activated 5-HT neurons only at 60-min duration. In contrast, c-Fos expression in CRF neurons in the PVN was enhanced in an intensity-dependent manner, regardless of exercise duration. c-Fos expression in 5-HT neurons in the DRN induced by the acute treadmill running for 30 or 60 min, but not 15 min, was positively correlated with the time spent on the open arms in the EPM and was negatively correlated with the immobility time in the FST. These results suggest an interaction between exercise intensity and duration on the antidepressant effects of acute physical exercise.

Infectious Disease Emergency Specialist (IDES) Training Program in Japan: an innovative governmental challenge to respond to global public health emergencies.

In 2015, Japan created a unique governmental program to train experts in health emergencies called Infectious Disease Emergency Specialist (IDES). This is a concept paper to set out the goal and structure of the program, and to describe the achievement and the way forward to further contribute to global health security. The IDES program background, mission, structure, achievement, and future directions were reviewed and discussed by the IDES trainees, graduates, and program coordinators/supervisors. Since 2015, thirteen Japanese medical doctors have graduated from the program while five are currently in training. The IDES core competencies were identified in the context of a wide range of skillsets required for health emergencies. A large national and global network has been created through the training. Coordinated work with surge capacity of experts is of paramount importance to prepare for and respond to public health emergencies. The IDES program can be a good model to many other governments, and contribute to global health security.

Prevalence of syphilis, gonorrhoea and chlamydia in women in Fiji, the Federated States of Micronesia, Papua New Guinea and Samoa, 1995-2017: Spectrum-STI model estimates.

OBJECTIVE: To estimate prevalence levels of and time trends for active syphilis, gonorrhoea and chlamydia in women aged 15-49 years in four countries in the Pacific (Fiji, the Federated States of Micronesia [FSM], Papua New Guinea [PNG] and Samoa) to inform surveillance and control strategies for sexually transmitted infections (STIs). METHODS: The Spectrum-STI model was fitted to data from prevalence surveys and screenings of adult female populations collected during 1995-2017 and adjusted for diagnostic test performance and to account for undersampled high-risk populations. For chlamydia and gonorrhoea, data were further adjusted for age and differences between urban and rural areas. RESULTS: Prevalence levels were estimated as a percentage (95% confidence interval). In 2017, active syphilis prevalence was estimated in Fiji at 3.89% (2.82 to 5.06), in FSM at 1.48% (0.93 to 2.16), in PNG at 3.91% (1.67 to 7.24) and in Samoa at 0.16% (0.07 to 0.37). For gonorrhoea, the prevalence in Fiji was 1.63% (0.50 to 3.87); in FSM it was 1.59% (0.49 to 3.58); in PNG it was 11.0% (7.25 to 16.1); and in Samoa it was 1.61% (1.17 to 2.19). The prevalence of chlamydia in Fiji was 24.1% (16.5 to 32.7); in FSM it was 23.9% (18.5 to 30.6); in PNG it was 14.8% (7.39 to 24.7); and in Samoa it was 30.6% (26.8 to 35.0). For each specific disease within each country, the 95% confidence intervals overlapped for 2000 and 2017, although in PNG the 2017 estimates for all three STIs were below the 2000 estimates. These patterns were robust in the sensitivity analyses. DISCUSSION: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO's Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.

Stress drives deliberative tendencies by influencing vicarious trial and error in decision making.

Previous studies have reported the effects of stress on decision making. However, the wide range of findings make it difficult to identify the fundamental effects of stress on decision making and, therefore, how stress affects decision making remains unknown. To investigate the influence of stress on decision making, we employed "vicarious trial and error" (VTE), which refers to a rat's behavior of orienting the head toward options at a decision point. VTE is thought to reflect mental simulation for possible options preceding a decision. We examined effects of acute restraint stress on VTE in a T-maze choice task. VTE depended on learning and past reward outcomes. Acute restraint stress before rats ran the T-maze choice task induced VTE, especially in trials with low demand of VTE, and increased the number of head orientations and time spent during each VTE. On the other hand, stress did not affect task performance (probability of advantageous choice) and patterns of behavioral choice (win-stay lose-shift, exploration-exploitation). In addition, stress activated serotonergic and noradrenergic neurons in the dorsal raphe nucleus and locus coeruleus, which are modulators of impulsivity and attentional control in decision making. These results suggest that stress in decision making drives the VTE process, which may lead to deep consideration, over-thinking, and indecisiveness.

Effectiveness and Tolerability of Oral Amoxicillin in Pregnant Women with Active Syphilis, Japan, 2010-2018.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010-2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

The Spectrum-STI Groups model: syphilis prevalence trends across high-risk and lower-risk populations in Yunnan, China.

The Spectrum-STI model, structured by sub-groups within a population, was used in a workshop in Yunnan, China, to estimate provincial trends in active syphilis in 15 to 49-year-old adults. Syphilis prevalence data from female sex workers (FSW), men who have sex with men (MSM), and lower-risk women and men in Yunnan were identified through literature searches and local experts. Sources included antenatal care clinic screening, blood donor screening, HIV/STI bio-behavioural surveys, sentinel surveillance, and epidemiology studies. The 2017 provincial syphilis prevalence estimates were 0.26% (95% confidence interval 0.17-0.34%) in women and 0.28% (0.20-0.36%) in men. Estimated prevalence was 6.8-fold higher in FSW (1.69% (0.68-3.97%) than in lower-risk women (0.25% (0.18-0.35%)), and 22.7-fold higher in MSM (5.35% (2.74-12.47%) than in lower-risk men (0.24% (0.17-0.31%). For all populations, the 2017 estimates were below the 2005 estimates, but differences were not significant. In 2017 FSW and MSM together accounted for 9.3% of prevalent cases. These estimates suggest Yunnan's STI programs have kept the overall prevalence of syphilis low, but prevalence remains high in FSW and MSM. Strengthening efforts targeting FSW and MSM, and identification of other risk populations e.g. among heterosexual men, are critical to reduce syphilis.

Mortality and causes of death in people living with HIV in the era of combination antiretroviral therapy compared with the general population in Japan.

OBJECTIVES: To determine the mortality and causes of death in people living with HIV (PLHIV) in Japan. DESIGN: A prospective cohort study at AIDS Clinical Center, Tokyo, which treats approximately 10% of PLHIV in care in Japan. METHODS: Either PLHIV who visited our center for the first time between January 2005 and December 2014 or PLHIV who started their regular visit before January 2005 and visited us between January and March 2005 were included and followed by the end of 2016. Causes of death were defined according to the CoDe protocol. RESULTS: Two thousand, seven hundred and ninety-seven PLHIV were analysed with total of 18 858 person-years of follow-up, which constitutes 14% of the estimated number of PLHIV in care in Japan. One hundred and sixty-five (5.9%) PLHIV died with all-cause mortality rate of 8.75 per 1000 person-years. All-cause mortality rate for PLHIV in care in Japan was estimated to be 8.75 per 1000 person-years (95% CI 5.53-12.0). Among causes of death, AIDS-defining illnesses accounted for 39% and malignancy contributed to 47%. Standardized mortality ratio (SMR) for all-cause mortality, malignancy-related mortality, and suicide were 5.96 (95% CI 5.05-6.87), 7.76 (95% CI 6.02-9.51), and 3.24 (95% CI 1.54-4.94), respectively. Even among the patients who were diagnosed early or without history of AIDS, SMR was four times higher than the general population. CONCLUSION: Mortality of PLHIV, even among those with early diagnosis, is substantially higher than that of the general population in Japan, highlighting the importance of further efforts towards prevention, early diagnosis and prompt treatment initiation.

Central nucleus of the amygdala is involved in induction of yawning response in rats.

Yawning behavior is characterized by mouth opening accompanied by deep inspiration, as well as arousal response, and is often observed not only in states of boredom or drowsiness, but also in stressful emotional situations in humans and animals. These phenomena suggest that yawning response may be an emotional behavior, possibly through activation of the central nucleus of amygdala (CeA), which is a critical region for emotional responses. However, the involvement of the CeA in triggering yawning remains unknown. Here, we investigated whether neuronal activation of the CeA by microinjection of L-glutamate into the CeA is able to induce stereotyped yawning responses in anesthetized, spontaneously breathing rats. In addition, we assessed the effects of the CeA stimulation on the activation of oxytocin (OT) and CRF (corticotropin-releasing factor) neurons in the paraventricular nucleus of the hypothalamus (PVN), which is responsible for induction of yawning, using c-Fos immunohistochemistry. Microinjection of L-glutamate into the CeA causes an initial depressor response in the blood pressure and an arousal shift on the electrocorticogram followed by a single inspiration, which is the same as the typical pattern of the stereotyped yawning response induced by the PVN stimulation. In addition, the CeA stimulation activated the neuronal activities of both OT and CRF neurons in the PVN, as well as yawning responses. These results indicate that activation of the CeA is involved in the induction of yawning response, suggesting that yawning is an emotional behavior.

Case Report: Hemophagocytic Lymphohistiocytosis Caused by Disseminated Histoplasmosis in a Venezuelan Patient with HIV and Epstein-Barr Virus Reactivation Who Traveled to Japan.

We describe a Venezuelan visitor to Japan who was diagnosed with hemophagocytic lymphohistiocytosis (HLH). The patient was also diagnosed with human immunodeficiency virus (HIV) and Epstein-Barr virus infection by the Western blot and polymerase chain reaction (PCR) tests, respectively. The cause of HLH was considered to be these two infections at first; however, the patient did not recover with antiretroviral/anti-herpes virus therapy. Thereafter, diagnosis of disseminated histoplasmosis was confirmed with an antigen detection test, culture, and PCR test of blood, urine, and bone marrow, and the patient improved gradually after the initiation of liposomal amphotericin B. This case highlights the importance of ruling out endemic mycosis as a cause of HLH even if other probable causes exist in patients from endemic areas.

Tenofovir nephrotoxicity among Asians living with HIV: review of the literature.

Tenofovir disoproxil fumarate (TDF), prodrug of tenofovir (TFV), is one of the most widely used nucleotide reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infection in resource-rich and resource-limited settings with proven efficacy and safety, and also for the treatment of hepatitis B infections. However, TDF can cause renal proximal tubular dysfunction and also reduces estimated glomerular filtration rate (eGFR) more than other NRTIs. To date, TDF-associated renal dysfunction is generally regarded as mild and tolerable. However, it is notable that low body weight is one of the risk factors for TFV nephrotoxicity and that Asians are generally of smaller body stature and can be susceptible to such nephrotoxicity, as shown in several cohort studies. Until tenofovir alafenamide (TAF), another prodrug of TFV with minimal renal toxicity, becomes widely accessible for people living with HIV and replaces TDF, it is warranted that physicians who prescribe TDF have a good understanding of TFV nephrotoxicity. This paper reviews recent literature on TFV nephrotoxicity among people living with HIV especially focusing on Asians who might be susceptible to TFV nephrotoxicity due to their lower body weight and discusses implications for clinical care and future directions.