A mathematical model for the transmission of co-infection with COVID-19 and kidney disease.

The world suffers from the acute respiratory syndrome COVID-19 pandemic, which will be scary if other co-existing illnesses exacerbate it. The co-occurrence of the COVID-19 virus with kidney disease has not been available in the literature. So, further research needs to be conducted to reveal the transmission dynamics of COVID-19 and kidney disease. This study aims to create mathematical models to understand how COVID-19 interacts with kidney diseases in specific populations. Therefore, the initial step was to formulate a deterministic Susceptible-Infected-Recovered (SIR) mathematical model to depict the co-infection dynamics of COVID-19 and kidney disease. A mathematical model with seven compartments has been developed using nonlinear ordinary differential equations. This model incorporates the invariant region, disease-free and endemic equilibrium, along with the positivity solution. The basic reproduction number, calculated via the next-generation matrix, allows us to assess the stability of the equilibrium. Sensitivity analysis is also utilised to understand the influence of each parameter on disease spread or containment. The results show that a surge in COVID-19 infection rates and the existence of kidney disease significantly enhances the co-infection risks. Numerical simulations further clarify the potential outcomes of treating COVID-19 alone, kidney disease alone, and co-infected cases. The study of the potential model can be utilised to maximise the benefits of simulation to minimise the global health complexity of COVID-19 and kidney disease.

Smokeless tobacco consumption and its association with risk factors of chronic kidney disease in rural and peri-urban Bangladesh.

INTRODUCTION: Compared to smoking, which has major consequences in chronic kidney disease (CKD) initiation and progression, smokeless tobacco (SLT) consumption is considered to have fewer health consequences. We investigated the prevalence of SLT consumption and its association with risk factors of CKD in a rural and peri-urban Bangladeshi population. METHODS: Using random sampling we recruited 872 adults in 2020, from the Mirzapur Demographic Surveillance System of Bangladesh, who had resided in the area for at least five years. Interviews using a semi-structured questionnaire, physical examination and anthropometric measurements were done, followed by blood and urine testing. The blood and urine tests were repeated in selected participants after three months as per the CKD Epidemiology Collaboration equation. RESULTS: The prevalence of SLT consumption was 29%. Being aged ≥46 years (OR=7.10; 95% CI: 4.79-10.94), female (OR=1.64; 95% CI: 1.21-2.22), housewife (OR=1.82; 95% CI: 1.35-2.45), farmer (OR=1.71; 95% CI: 1.06-2.76), widow (OR=3.40; 95% CI: 2.24-5.17), and having no formal schooling (OR=4.91; 95% CI: 3.59-6.72), family income of <$100/month (OR=1.66; 95% CI: 1.13-2.43), sleeping duration <7 hours per day (OR=2.33; 95% CI: 1.70-3.19), were associated with a significantly higher odds of SLT consumption. However, being aged 31-45 years (OR=0.25; 95% CI: 0.16-0.38) had significantly lower odds of being an SLT consumer. Among the diseases investigated, undernutrition (OR=1.63; 95% CI: 1.15-2.33), hypertension (OR=1.52; 95% CI: 1.13-2.05), anemia (OR=1.94; 95% CI: 1.39-2.71) and CKD (OR=1.62; 95% CI: 1.15-2.27) were significantly associated with SLT consumption. In the multivariable analysis, being aged 31-45 years (AOR=3.06; 95% CI: 1.91-4.90), ≥46 years (AOR=15.69; 95% CI: 4.64-53.09) and having no formal schooling (AOR=2.47; 95% CI: 1.72-3.55) were found to have a significant association with being an SLT consumer. CONCLUSIONS: SLT consumption is associated with most of the established risk factors of CKD within the studied population.

Feasibility and acceptability of bubble continuous positive airway pressure oxygen therapy for the treatment of childhood severe pneumonia and hypoxaemia in Bangladeshi children.

Background: Effective management of hypoxaemia is key to reducing pneumonia deaths in children. In an intensive care setting within a tertiary hospital in Bangladesh, bubble continuous positive airway pressure (bCPAP) oxygen therapy was beneficial in reducing deaths in this population. To inform a future trial, we investigated the feasibility of introducing bCPAP in this population in non-tertiary/district hospitals in Bangladesh. Methods: We conducted a qualitative assessment using a descriptive phenomenological approach to understand the structural and functional capacity of the non-tertiary hospitals (Institute of Child and Mother Health and Kushtia General Hospital) for the clinical use of bCPAP. We conducted interviews and focus group discussions (23 nurses, seven physicians, 14 parents). We retrospectively (12 months) and prospectively (three months) measured the prevalence of severe pneumonia and hypoxaemia in children attending the two study sites. For the feasibility phase, we enrolled 20 patients with severe pneumonia (age two to 24 months) to receive bCPAP, putting in place safeguards to identify risk. Results: Retrospectively, while 747 of 3012 (24.8%) children had a diagnosis of severe pneumonia, no pulse oxygen saturation information was available. Of 3008 children prospectively assessed with pulse oximetry when attending the two sites, 81 (3.7%) had severe pneumonia and hypoxaemia. The main structural challenges to implementation were the inadequate number of pulse oximeters, lack of power generator backup, high patient load with an inadequate number of hospital staff, and inadequate and non-functioning oxygen flow meters. Functional challenges were the rapid turnover of trained clinicians in the hospitals, limited post-admission routine care for in-patients by hospital clinicians due to their extreme workload (particularly after official hours). The study implemented a minimum of four hourly clinical reviews and provided oxygen concentrators (with backup oxygen cylinders), and automatic power generator backup. Twenty children with a mean age of 6.7 (standard deviation (SD) = 5.0)) months with severe pneumonia and hypoxaemia (median (md) SpO2 = 87% in room air, interquartile range (IQR) = 85-88)) with cough (100%) and severe respiratory difficulties (100%) received bCPAP oxygen therapy for a median of 16 hours (IQR = 6-16). There were no treatment failures or deaths. Conclusions: Implementation of low-cost bCPAP oxygen therapy is feasible in non-tertiary/district hospitals when additional training and resources are allocated.

Platelet lysate can support the development of a 3D-engineered skin for clinical application.

Safety concerns associated with foetal bovine serum (FBS) have restricted its translation into clinics. We hypothesised that platelet lysate (PL) can be utilised as a safe alternative to produce serum-free 3D-engineered skin. PL supported a short-term expansion of fibroblasts, with negligible replication-induced senescence and directed epidermal stratification. PL-expanded fibroblasts were phenotypically separated into three subpopulations of CD90+FAP+, CD90+FAP- and CD90-FAP+, based on CD90 (reticular marker) and FAP (papillary marker) expression profile. PL drove the expansion of the intermediate CD90+ FAP+ subpopulation in expense of reticular CD90+FAP-, which may be less fibrotic once grafted. The 3D-engineered skin cultured in PL was analysed by immunofluorescence using specific markers. Detection of ColIV and LMN-511 confirmed basement membrane. K10 confirmed near native differentiation pattern of neo-epidermis. CD29- and K5-positive interfollicular stem cells were also sustained. Transmission and scanning electron microscopies detailed the ultrastructure of the neo-dermis and neo-epidermis. To elucidate the underlying mechanism of the effect of PL on skin maturation, growth factor contents in PL were measured, and TGF-ß1 was identified as one of the most abundant. TGF-ß1 neutralising antibody reduced the number of Ki67-positive proliferative cells, suggesting TGF-ß1 plays a role in skin maturation. Moreover, the 3D-engineered skin was exposed to lucifer yellow on days 1, 3 and 5. Penetration of lucifer yellow into the skin was used as a semi-quantitative measure of improved barrier function over time. Our findings support the concept of PL as a safe and effective serum alternative for bioengineering skin for cell therapies.

Neuropharmacological Effects of Chassalia curviflora (Rubiaceae) Leaves in Swiss Albino Mice Model.

The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of Chassalia curviflora (C. curviflora) in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length (P<0.05) in studies on thiopental sodium-induced sleeping time at dosages of 100 and 200 mg/kg and a significant decrease (P<0.05) was found in terms of unconstrained locomotor and explorative activities in both hole crossing and open field tests at dosages of 100 and 200 mg/kg. Furthermore, the extracts increased sleeping time with a dosage-dependent onset of action. The hole-board test extracts also reduced the number of head dips at dosages of 100 and 200 mg/kg (P<0.05). It was found in this study that C. curviflora had the best neuropharmacological properties at a dosage of 200 ml/kg. Our findings also showed that all of the extracts from C. curviflora were experimentally active in an in vivo model. The study results suggested that the leaves had strong anti-depressant and hypnotic CNS properties that might be exploited for neuropharmacological adjuvant therapy in conventional medicine. However, pharmacological studies are warranted to explore the active substances and the mode of action.

Heat Wave and Bushfire Meteorology in New South Wales, Australia: Air Quality and Health Impacts.

The depletion of air quality is a major problem that is faced around the globe. In Australia, the pollutants emitted by bushfires play an important role in making the air polluted. These pollutants in the air result in many adverse impacts on the environment. This paper analysed the air pollution from the bushfires from November 2019 to July 2020 and identified how it affects the human respiratory system. The bush fires burnt over 13 million hectares, destroying over 2400 buildings. While these immediate effects were devastating, the long-term effects were just as devastating, with air pollution causing thousands of people to be admitted to hospitals and emergency departments because of respiratory complications. The pollutant that caused most of the health effects throughout Australia was Particulate Matter (PM) PM2.5 and PM10. Data collection and analysis were covered in this paper to illustrate where and when PM2.5 and PM10, and other pollutants were at their most concerning levels. Susceptible areas were identified by analysing environmental factors such as temperature and wind speed. The study identified how these pollutants in the air vary from region to region in the same time interval. This study also focused on how these pollutant distributions vary according to the temperature, which helps to determine the relationship between the heatwave and air quality. A computational model for PM2.5 aerosol transport to the realistic airways was also developed to understand the bushfire exhaust aerosol transport and deposition in airways. This study would improve the knowledge of the heat wave and bushfire meteorology and corresponding respiratory health impacts.

Nanoparticle transport and deposition in a heterogeneous human lung airway tree: An efficient one path model for CFD simulations.

Understanding nano-particle inhalation in human lung airways helps targeted drug delivery for treating lung diseases. A wide range of numerical models have been developed to analyse nano-particle transport and deposition (TD) in different parts of airways. However, a precise understanding of nano-particle TD in large-scale airways is still unavailable in the literature. This study developed an efficient one-path numerical model for simulating nano-particle TD in large-scale lung airway models. This first-ever one-path numerical approach simulates airflow and nano-particle TD in generations 0-11 of the human lung, accounting for 93% of the whole airway length. The one-path model enables the simulation of particle TD in many generations of airways with an affordable time. The particle TD of 5 nm, 10 nm and 20 nm particles is simulated at inhalation flow rates for two different physical activities: resting and moderate activity. It is found that particle deposition efficiency of 5 nm particles is 28.94% higher than 20 nm particles because of the higher dispersion capacity. It is further proved that the diffusion mechanism dominates the particle TD in generations 0-11. The deposition efficiency decreases with the increase of generation number irrespective of the flow rate and particle size. The effects of the particle size and flow rate on the escaping rate of each generation are opposite to the corresponding effects on the deposition rate. The quantified deposition and escaping rates at generations 0-11 provide valuable guidelines for drug delivery in human lungs.

A platelet-derived hydrogel improves neovascularisation in full thickness wounds.

Platelets are a reservoir of growth factors, cytokines and chemokines involved in spontaneous wound repair. In this study, a platelet-rich and fibrin-rich hydrogel was generated from expired platelet components that would have otherwise been transfused. The material contained physiological concentrations of transforming growth factor ß1 (TGF-ß1, platelet-derived growth factor AB (PDGF-AB), PDGF-BB, insulin-like growth factor-1 (IGF-1), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF). The effect of the hydrogel on wound repair was investigated in SKH-1 mice. Full thickness dorsal wounds were created on the mice and treated with the hydrogel at various concentrations. Immunohistochemical staining with CD31 (endothelial cell marker) revealed that wounds treated with the hydrogel showed significantly enhanced vascularisation in the wound bed. Moreover, high levels of interleukin-6 (IL-6) and KC (IL-8 functional homologue) in treated wounds were sustained over a longer period of time, compared to untreated wounds. We postulate that sustained IL-6 is a driver, at least partly, of enhanced vascularisation in full thickness wounds treated with the hydrogel. Future work is needed to explore whether this hydrogel can be utilised as a treatment option when vascularisation is a critical limitation. STATEMENT OF SIGNIFICANCE: The economic cost of wound repair is estimated in billions of dollars each year. In many cases time required to vascularise wounds is a major contributor to slow wound repair. In this study, we developed a blood-derived platelet- and fibrin-rich hydrogel. It contains a number of growth factors actively involved in spontaneous wound healing. This hydrogel significantly improved dermal repair and vascularisation in a full-thickness wound mouse model. This study provides an action mechanism for modulation of localised inflammation.

Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies.

Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.

Does work-family balance mediate the relationship between work-family conflicts and job satisfaction of academicians?

Extreme workloads and strict work schedules make an individual cut their time and energy from their family domain, which may create a conflict, and this situation is called Work-Family Conflict (W-FC). Besides this, Work Family Balance (WFB) and Job Satisfaction (JS) issues are significant for academics because they have to play two roles (Job and Family) at the same time. This paper's fundamental objective was to investigate the indirect effect (mediation) of WFB through both forms of W-FC and JS. Following the convenience sampling technique, 250 married academicians from different private universities were considered for the sample size. Analysis of Moment Structures (AMOS) and Statistical Package for the Social Sciences (SPSS) was used to complete the data analyses. The outcomes of this study showed that out of the two forms, only W to F has significant adverse effects on JS. Also, it was found that to some extent, WFB showed a partial mediating effect only between W to FC and JS, whereas there was no mediating effect through F to WC and JS. These findings will help both academicians and higher authorities of private universities in Bangladesh. The higher authorities and decision-makers of the private universities in Bangladesh can identify the sources of W-FCs and take the necessary steps to mitigate the level of W-FCs.

Serological Evidence of Avian Influenza in Captive Wild Birds in a Zoo and Two Safari Parks in Bangladesh.

Avian influenza (AI) is endemic and frequently causes seasonal outbreaks in winter in Bangladesh due to high pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2. Among avian influenza A viruses (AIV), H5, H7, and H9 subtypes have the most zoonotic potential. Captive birds in zoos and safari parks are used for educational, recreational, breeding, and conservational purposes in Bangladesh. To screen for AIV in captive birds to assess potential public health threats, we conducted a cross-sectional study in two safari parks and one zoo in Bangladesh for four months, from November to December 2013 and from January to February 2014. We collected blood samples, oropharyngeal, and cloacal swabs from 228 birds. We tested serum samples for AIV antibodies using competitive enzyme-linked immunosorbent assay (c-ELISA) and AIV sero-subtype H5, H7, and H9 using hemagglutination inhibition (HI) test. Swab samples were tested for the presence of avian influenza viral RNA using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Across all the samples, AIV antibody prevalence was 9.7% (95% CI: 6.1-14.2, n = 228) and AIV HA subtype H5, H7 and H9 sero-prevalence was 0% (95% CI: 0-1.6, n = 228), 0% (95% CI: 0-1.6, n = 228) and 6.6% (95% CI: 3.72-10.6, n = 228), respectively. No AI viral RNA (M-gene) was detected in any swab sample (0%, 95% CI: 0-1.6, n = 228). Birds in the Safari park at Cox's Bazar had a higher prevalence in both AIV antibody prevalence (13.5%) and AIV H9 sero-prevalence (9.6%) than any of the other sites, although the difference was not statistically significant. Among eight species of birds, Emu (Dromaius novaehollandiae) had the highest sero-positivity for both AIV antibody prevalence (26.1%) and AIV H9 prevalence (17.4%) followed by Golden pheasant (Chrysolophus pictus) with AIV antibody prevalence of 18.2% and AIV H9 prevalence of 11.4%. Our results highlight the presence of AI antibodies indicating low pathogenic AIV mingling in captive birds in zoos and safari parks in Bangladesh. Continuous programmed surveillance is therefore recommended to help better understand the diversity of AIVs and provide a clear picture of AI in captive wild birds, enabling interventions to reduce the risk of AIV transmission to humans.

Omega-3 fatty acids in contrast to omega-6 protect against pneumococcal pneumonia.

PURPOSE: The aim of this study was to assess if long-term supplementation of omega-3 fatty acids or a diet rich in omega-6 fatty acids ameliorates disease severity in a murine model of pneumococcal pneumonia. We hypothesize that long-term dietary supplementation of omega-3 fatty acids will reduce inflammation, disease severity and improve survival compared to omega-6 fatty acids. METHODS: Mice receiving diets supplemented with Omega-3 or Omega-6 for two months were intranasally infected with Streptococcus pneumoniae. We analyzed survival, bacterial burden, histopathology and inflammatory biomarkers. RESULTS: Our results showed that Omega-3 supplementation had increased survival (p = 0.005), less bacteremia (p = 0.0001) and lower bacterial burden in the lungs (p = 0.0002) when compared to the Omega-6 supplementation. Overall, Omega-3 reduced lung pathology, in particular peribronchial inflammation and cell death. Analyses of lung homogenates showed the Omega-3 cohort had decreased levels of the inflammatory cytokine interleukin-6 and an increase in anti-inflammatory cytokine interleukin-10. CONCLUSIONS: Supplementation of mouse diets with Omega-3 fatty acids improved survival, bacterial invasion in the blood and lungs as well as decreased overall lung tissue inflammation and cell death when compared to the Omega-6 supplemented diets. Translation of these findings in humans may improve outcomes of patients at risk for pneumonia.

Nurse-Led Collaborative Management Using Telemonitoring Improves Quality of Life and Prevention of Rehospitalization in Patients with Heart Failure.

The effects of disease management using telemonitoring for patients with heart failure (HF) remain controversial. Hence, we embedded care coordination and enhanced collaborative self-management through interactive communication via a telemonitoring system (collaborative management; CM). This study evaluated whether CM improved psychosocial status and prevented rehospitalization in patients with HF in comparison with self-management education (SM), and usual care (UC).We randomly allocated 59 patients into 3 groups; UC (n = 19), SM (n = 20), and CM (n = 20). The UC group received one patient education session, and the SM and CM groups participated in disease management programs for 12 months. The CM group received telemonitoring concurrently. All groups were followed up for another 12 months. Data were collected at baseline and at 6, 12, 18, and 24 months.The primary endpoint was quality of life (QOL). Secondary endpoints included self-efficacy, self-care, and incidence of rehospitalization. The QOL score improved in CM compared to UC at 18 and 24 months (P < 0.05). There were no significant differences among the 3 groups in self-efficacy and self-care. However, compared within each group, only the CM had significant changes in self-efficacy and in self-care (P < 0.01). Rehospitalization rates were high in the UC (11/19; 57.9%) compared with the SM (5/20; 27.8%) and CM groups (4/20; 20.0%). The readmission-free survival rate differed significantly between the CM and UC groups (P = 0.020).We conclude that CM has the potential to improve psychosocial status in patients with HF and prevent rehospitalization due to HF.

Structural characteristics of a mitochondrial control region from M yotis bat (Vespertilionidae) mitogenomes based on sequence datasets.

The datasets included sequences of a control region from Myotis bat mitogenomes. The control region (1706-2005 bp) of the Myotis mitogenomes was divided into three domains similar to that of other mammals, which included the common conserved blocks (ETAS domain, Central domain, and CSB domain). Several long tandem repeat sequences were present between the upstream of control regions and ETAS1. The size, base composition, and copy number of the long tandem repeat sequences differed between the Myotis species. Short tandem repeat sequences were also found between CSB1 and CSB2 in the CSB domain.

Inositol 1,4,5-Trisphosphate Receptors in Hypertension.

Chronic hypertension remains a major cause of global mortality and morbidity. It is a complex disease that is the clinical manifestation of multiple genetic, environmental, nutritional, hormonal, and aging-related disorders. Evidence supports a role for vascular aging in the development of hypertension involving an impairment in endothelial function together with an alteration in vascular smooth muscle cells (VSMCs) calcium homeostasis leading to increased myogenic tone. Changes in free intracellular calcium levels ([Ca2+] i ) are mediated either by the influx of Ca2+ from the extracellular space or release of Ca2+ from intracellular stores, mainly the sarcoplasmic reticulum (SR). The influx of extracellular Ca2+ occurs primarily through voltage-gated Ca2+ channels (VGCCs), store-operated Ca2+ channels (SOC), and Ca2+ release-activated channels (CRAC), whereas SR-Ca2+ release occurs through inositol trisphosphate receptor (IP3R) and ryanodine receptors (RyRs). IP3R-mediated SR-Ca2+ release, in the form of Ca2+ waves, not only contributes to VSMC contraction and regulates VGCC function but is also intimately involved in structural remodeling of resistance arteries in hypertension. This involves a phenotypic switch of VSMCs as well as an alteration of cytoplasmic Ca2+ signaling machinery, a phenomena tightly related to the aging process. Several lines of evidence implicate changes in expression/function levels of IP3R isoforms in the development of hypertension, VSMC phenotypic switch, and vascular aging. The present review discusses the current knowledge of these mechanisms in an integrative approach and further suggests potential new targets for hypertension management and treatment.

Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

WHAT IS KNOWN AND OBJECTIVE: Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. METHODS: Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. RESULTS AND DISCUSSION: Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P < .01). WHAT IS NEW AND CONCLUSION: Inconsistent reporting patterns were observed more between brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported.

Population health and regional variations of disease burden in Japan, 1990-2015: a systematic subnational analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Japan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level. METHODS: We used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations. FINDINGS: Life expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from -32·4% (-34·8 to -30·0) to -22·0% (-20·4 to -20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015. INTERPRETATION: Japan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment. FUNDING: Bill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund.

Mechanistic Insight into Salt Tolerance of Acacia auriculiformis: The Importance of Ion Selectivity, Osmoprotection, Tissue Tolerance, and Na+ Exclusion.

Salinity, one of the major environmental constraints, threatens soil health and consequently agricultural productivity worldwide. Acacia auriculiformis, being a halophyte, offers diverse benefits against soil salinity; however, the defense mechanisms underlying salt-tolerant capacity in A. auriculiformis are still elusive. In this study, we aimed to elucidate mechanisms regulating the adaptability of the multi-purpose perennial species A. auriculiformis to salt stress. The growth, ion homeostasis, osmoprotection, tissue tolerance and Na+ exclusion, and anatomical adjustments of A. auriculiformis grown in varied doses of seawater for 90 and 150 days were assessed. Results showed that diluted seawater caused notable reductions in the level of growth-related parameters, relative water content, stomatal conductance, photosynthetic pigments, proteins, and carbohydrates in dose- and time-dependent manners. However, the percent reduction of these parameters did not exceed 50% of those of control plants. Na+ contents in phyllodes and roots increased with increasing levels of salinity, whereas K+ contents and K+/Na+ ratio decreased significantly in comparison with control plants. A. auriculiformis retained more Na+ in the roots and maintained higher levels of K+, Ca2+ and Mg2+, and K+/Na+ ratio in phyllodes than roots through ion selective capacity. The contents of proline, total free amino acids, total sugars and reducing sugars significantly accumulated together with the levels of malondialdehyde and electrolyte leakage in the phyllodes, particularly at day 150th of salt treatment. Anatomical investigations revealed various anatomical changes in the tissues of phyllodes, stems and roots by salt stress, such as increase in the size of spongy parenchyma of phyllodes, endodermal thickness of stems and roots, and the diameter of root vascular bundle, relative to control counterparts. Furthermore, the estimated values for Na+ exclusion and tissue tolerance index suggested that A. auriculiformis efficiently adopted these two mechanisms to address higher salinity levels. Our results conclude that the adaptability of A. auriculiformis to salinity is closely associated with ion selectivity, increased accumulation of osmoprotectants, efficient Na+ retention in roots, anatomical adjustments, Na+ exclusion and tissue tolerance mechanisms.

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging.

Sarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with loss of motor neuron innervation, we investigated the potential for the histone deacetylase (HDAC) inhibitor butyrate to modulate age-related muscle loss. Consistent with previous studies, we found significant loss of hindlimb muscle mass in 26-month-old C57Bl/6 female mice fed a control diet. Butyrate treatment starting at 16 months of age wholly or partially protected against muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross-sectional area and prevented intramuscular fat accumulation in the old mice. In addition to the protective effect on muscle mass, butyrate reduced fat mass and improved glucose metabolism in 26-month-old mice as determined by a glucose tolerance test. Furthermore, butyrate increased markers of mitochondrial biogenesis in skeletal muscle and whole-body oxygen consumption without affecting activity. The increase in mass in butyrate-treated mice was not due to reduced ubiquitin-mediated proteasomal degradation. However, butyrate reduced markers of oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data is the first to show a beneficial effect of butyrate on muscle mass during aging and suggests HDACs contribute to age-related muscle atrophy and may be effective targets for intervention in sarcopenia and age-related metabolic disease.