Towards the elimination of HTLV-1 infection in Japan Nishijima, Takeshi; Shimada, Satoshi; Noda, Hiroyuki ...
The Lancet infectious diseases,
January 2019, 2019-01-00, 20190101, Letnik:
19, Številka:
1
Journal Article
Recenzirano
...counselling was made available for people living with HTLV-1 infection and associated diseases, and training materials and courses for health-care providers and counsellors were organised. ...the ...coordination of care for HTLV-1-associated diseases was strengthened, with better coordination between health-care facilities that care for patients with HTLV-1-associated diseases and the development of guidelines for the management of adult T-cell leukaemia-lymphoma and HAM-TSP. ...a public awareness campaign, in collaboration with Hataraku Saibou (Cells at Work!; a Japanese animation series), was launched in 2018.
•Hippocampal neuronal activation differs with exercise type of similar intensity.•Mouse hippocampal activity is activated more by treadmill than by rotarod exercise.•Exercise type is a key factor ...influencing exercise effects on the hippocampus.
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.
•Neuronal activities to acute exercise at different intensities were examined.•Changes in anxiety- and depressive-like behaviors by acute exercise were assessed.•Acute exercise with mild or low ...stress induces antidepressant/anxiolytic effects.
Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic–pituitary–adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30min of treadmill running at different speeds (high speed, 25m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high-speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high-speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects.
Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic ...infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients.
Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox's proportional hazards model was used to estimate hazard ratios (HR).
During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40-59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40-49, 50-59, 60-69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8-0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score.
Liver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40-59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.
•Microinjection of L-glutamate into the CeA caused the typical pattern of stereotyped yawning responses.•The CeA stimulation activated the neuronal activities of both OT and CRF neurons in the PVN, ...which are responsible for triggering yawning.•Yawning might be an emotional behavior, being based on neural mechanisms.
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.
•Body weight increases among Asian people living with human immunodeficiency virus following the initiation of antiretroviral therapy (ART).•Long-term weight gain following ART initiation depends on ...drug combination•The combination of dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine is associated with the greatest weight gain.•TAF-containing regimens are associated with the greatest weight gain.
To investigate changes in weight following the initiation of antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus (PLWH).
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.
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.
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.
Physical exercise can improve brain function, but the effects of exercise cessation are largely unknown. This study examined the time-course profile of hippocampal neurogenesis following exercise ...cessation. Male C57BL/6 mice were randomly assigned to either a control (Con) or an exercise cessation (ExC) group. Mice in the ExC group were reared in a cage with a running wheel for 8 wk and subsequently placed in a standard cage to cease the exercise. Exercise resulted in a significant increase in the density of doublecortin (DCX)-positive immature neurons in the dentate gyrus (at
). Following exercise cessation, the density of DCX-positive neurons gradually decreased and was significantly lower than that in the Con group at 5 and 8 wk after cessation, indicating that exercise cessation leads to a negative rebound in hippocampal neurogenesis. Immunohistochemistry analysis suggests that the negative rebound in neurogenesis is caused by diminished cell survival, not by suppression of cell proliferation and neural maturation. Neither elevated expression of ΔFosB, a transcription factor involved in neurogenesis regulation, nor increased plasma corticosterone, were involved in the negative neurogenesis rebound. Importantly, exercise cessation suppressed ambulatory activity, and a significant correlation between change in activity and DCX-positive neuron density suggested that the decrease in activity is involved in neurogenesis impairment. Forced treadmill running following exercise cessation failed to prevent the negative neurogenesis rebound. This study indicates that cessation of exercise or a decrease in physical activity is associated with an increased risk for impaired hippocampal function, which might increase vulnerability to stress-induced mood disorders.
Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently ...demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso-ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity.
Little information is available on the mortality and risk factors associated with death in disseminated non-tuberculous mycobacterial infection (dNTM) in HIV-infected patients in the ART-era.
In a ...single-center study, HIV-infected dNTM with positive NTM culture from sterile sites between 2000 and 2013 were analysed. The clinical characteristics at commencement of anti-mycobacterial treatment (baseline) were compared between those who survived and died.
Twenty-four patients were analyzed. The median CD4 27/μL (range 2-185). Mycobacterium avium and M. intracellulare accounted for 20 (83%) and 3 (13%) of isolated NTM. NTM bacteremia was diagnosed in 15 (63%) patients. Seven (29%) patients died, and NTM bacteremia was significantly associated with mortality (p = 0.022). The baseline CD4 count was significantly lower in the non-survivors than the survivors (median 7/μL versus 49, p = 0.034). Concomitant AIDS-defining diseases or malignancies were not associated with mortality. Immune-reconstitution syndrome (IRS) occurred to 19 (79%) patients (8 paradoxical and 11 unmasking), and prognosis tended to be better in unmasking-IRS than the other patients (n = 13) (p = 0.078). Patients with paradoxical-IRS had marginally lower CD4 count and higher frequency of bacteremia than those with unmasking-IRS (p = 0.051, and 0.059). Treatment with systemic corticosteroids was applied in 63% and 55% of patients with paradoxical and unmasking-IRS, respectively.
dNTM in HIV-infected patients resulted in high mortality even in the ART-era. NTM bacteremia and low CD4 count were risk factors for death, whereas patients presented with unmasking-IRS had marginally better prognosis. IRS occurred in 79% of the patients, suggesting difficulty in the management of dNTM.
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.
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