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Summary This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. Background Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. Objective This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. Methods This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients’ conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. Results The mean observation period was 4.0 years (range 0–7 years). The average age at the time of admission was 82 years (range 60–101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82–91), low risk (92–98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate ( p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [ p = 0.004]). Conclusions We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Are agroforestry systems still realistic methods to balance forestation and livelihood for small-scale farmers? To answer this question, the author continuously monitored a 48-year agroforestry management system from the perspective of land management history and tree growth. The study plot is located in Tenggarong district, East Kalimantan Province, Borneo, Indonesia. The site covers a total area of 2 ha and has been managed by a farmer since 1974. Chronological data on the cultivated crops and tree growth were collected through direct observations and mensuration by local university researchers. As of 2022, an Agathis forest with a standing stock volume of 632.4 m3 had been created by agroforestry practices. On the other hand, the average income he generated was US$ 1231/year from 1974 to 2016. The gross cash income of the farmer was below or at the same level as the provincial minimum wage for 23 years or 48% of the entire management period. The results of the current study showed that the main income source changed over the years. This change was influenced by many factors, such as family member life stage, social demand supported by the increasing population, Agathis tree growth and farmer age. In response to change, the farmer planted many kinds of crops and selected the most profitable commodity in each period. Due to this trial-and-selection approach, his income source was diversified and generated a stable cash income not only throughout the year, but also throughout the 48 years management period. The results of the current case study showed that the agroforestry system is a realistic method for forestation and long-term management for small-scale farmer. On the other hand, it is not the optimal method if the purpose is to maximize cash income.

Astrocytic Ca 2+ signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca 2+ imaging showed that nodes were biochemical compartments and Ca 2+ microdomains. Mapping astrocytic Ca 2+ signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on the nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes. Astrocytic Ca 2+ signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. Here, the authors report the organization of astrocytes at nanoscale level and identify nodes as a functional astrocytic component of tripartite synapses.

Mercury (Hg) is one of the most harmful metals and has been a public health concern according to the World Health Organization (WHO). Artisanal and small-scale gold mining (ASGM) is the world’s fastest-growing source of Hg and can release Hg into the atmosphere, hydrosphere, and geosphere. Hg has been widely used in ASGM industries throughout Southeast Asia countries, including Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, and Thailand. Here, 16 relevant studies were systematically searched by performing the PRISMA flow, combining the keywords of “Hg”, “ASGM”, and relevant study areas. Mercury concentrations exceeding the WHO and United States Environmental Protection Agency guideline values were reported in environmental (i.e., air, water, and soil) and biomonitoring samples (i.e., plants, fish, and human hair). ASGM-related health risks to miners and nonminers, specifically in Indonesia, the Philippines, and Myanmar, were also assessed. The findings indicated severe Hg contamination around the ASGM process, specifically the gold-amalgamation stage, was significantly high. To one point, Hg atmospheric concentrations from all observed studies was shown to be extremely high in the vicinity of gold operating areas. Attentions should be given regarding the public health concern, specifically for the vulnerable groups such as adults, pregnant women, and children who live near the ASGM activity. This review summarizes the effects of Hg in Myanmar and other Southeast Asian countries. In the future, more research and assessment will be required to investigate the current and evolving situation in ASGM communities.

Background Tension-type headache (TTH) and migraine are prevalent neurological conditions in children and adolescents that significantly impact activity of daily living (ADL) and quality of life (QOL). Although physical therapy targeting cervical myofascial trigger points (MTrPs) on TTH and migraine has been extensively studied in adults, the efficacy in pediatric patients remains unexplored. The aim of this study is to reveal the effect of physical therapy integrated with pharmacotherapy on TTH and migraine in children and adolescents. Methods We conducted a prospective, observational cohort study recruiting consecutive patients aged 6 to 18 years with TTH and migraine with cervical MTrPs. They were classified into 4 types of headaches: frequent episodic TTH (FRTTH), chronic TTH (CTTH), episodic migraine (EM) and chronic migraine (CM). The once-weekly 40-minutes physical therapy session integrated with pharmacotherapy (integrated physical therapy) was continued until the treatment goals (headache days per week less than 2 days, headache impact test-6 (HIT-6) score to below of 50, and the ability to attend school daily) was achieved. Multifaceted assessments including headache frequency (headache days per week), headache intensity using the Visual Analogue Scale (VAS), pain catastrophizing score (PCS), hospital anxiety and depression scale (HADS) score, HIT-6 scores, and EuroQol 5 dimensions 5-level questionnaire (EQ-5D-5 L) scores, were conducted to evaluate the treatment effects. Results 161 patients were enrolled in this study. 106 patients (65.8%) were diagnosed with TTH: 70 (66.8%) with FETHH, 36 (34.0%) with CTTH, and 55 patients (34.2%) were diagnosed with migraine: 43 patients (78.2%) with EM, 12 patients (21.8%) with CM. We observed significant improvements in headache frequency, headache intensity, PCS, HADS score, HIT-6 scores, and EQ-5D-5 L scores before and after the treatment in all 4 types of headaches. The average number of sessions required to achieve the treatment goals was 4 times (weeks) for patients with FETTH and EM, 5.5 for those with CTTH, and 7.5 for those with chronic migraine. Conclusion The integrated physical therapy on pediatric TTH and migraine patients with the cervical MTrPs was significantly effective in reducing headache symptoms and improving ADL and QOL.

Astrocytes, a glial cell type of the central nervous system, have emerged as detectors and regulators of neuronal information processing. Astrocyte excitability resides in transient variations of free cytosolic calcium concentration over a range of temporal and spatial scales, from sub-microdomains to waves propagating throughout the cell. Despite extensive experimental approaches, it is not clear how these signals are transmitted to and integrated within an astrocyte. The localization of the main molecular actors and the geometry of the system, including the spatial organization of calcium channels IP3R, are deemed essential. However, as most calcium signals occur in astrocytic ramifications that are too fine to be resolved by conventional light microscopy, most of those spatial data are unknown and computational modeling remains the only methodology to study this issue. Here, we propose an IP3R-mediated calcium signaling model for dynamics in such small sub-cellular volumes. To account for the expected stochasticity and low copy numbers, our model is both spatially explicit and particle-based. Extensive simulations show that spontaneous calcium signals arise in the model via the interplay between excitability and stochasticity. The model reproduces the main forms of calcium signals and indicates that their frequency crucially depends on the spatial organization of the IP3R channels. Importantly, we show that two processes expressing exactly the same calcium channels can display different types of calcium signals depending on the spatial organization of the channels. Our model with realistic process volume and calcium concentrations successfully reproduces spontaneous calcium signals that we measured in calcium micro-domains with confocal microscopy and predicts that local variations of calcium indicators might contribute to the diversity of calcium signals observed in astrocytes. To our knowledge, this model is the first model suited to investigate calcium dynamics in fine astrocytic processes and to propose plausible mechanisms responsible for their variability.

The continuing emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be ameliorated by infection prevention through daily diet. In this study, we examined the anti-SARS-CoV-2 activity of 10 commercially available dairy products. They did not show any cytotoxicity against VeroE6/transmembrane protease serine 2 (TMPRSS2) cells (CC50 > 4 mg/ml). Importantly, these cells were checked using the cytopathic effect (CPE) assay, and 4 mg/ml dairy products reduced virus-induced CPE by more than 30%. Notably, Icreo akachan milk, an infant formula, showed the highest antiviral activity with an IC50 of 1.4 mg/ml. We assessed the effects of the dairy products on the entry of SARS-CoV-2 pseudovirus. R1 and Yakult, lactic acid bacterial beverages, inhibited viral entry with IC50 of 2.9 and 3.5 mg/ml, respectively. Collectively, these results indicate that commercially available dairy products moderately inhibit SARS-CoV-2 infection and may reduce the incidence of viral infections.

A patient in Japan with HIV began antiretroviral therapy because of acute hepatitis B virus (HBV) 15 years ago, with low hepatitis B surface antibody, and experienced breakthrough HBV reactivation 4 months after switching from bictegravir/emtricitabine/tenofovir alafenamide to cabotegravir/rilpivirine. An immune escape mutation, E164V, was identified in the isolated HBV DNA.

We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC50 values of 0.53 ± 0.10 μM and 2.37 ± 0.25 μM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC50 = 0.06 ± 0.01 μM) and onnamide B (IC50 = 0.23 ± 0.06 μM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.