Paradoxical Mitophagy Regulation by PINK1 and TUFm.

Aberrant mitophagy has been implicated in a broad spectrum of disorders. PINK1, Parkin, and ubiquitin have pivotal roles in priming mitophagy. However, the entire regulatory landscape and the precise control mechanisms of mitophagy remain to be elucidated. Here, we uncover fundamental mitophagy regulation involving PINK1 and a non-canonical role of the mitochondrial Tu translation elongation factor (TUFm). The mitochondrion-cytosol dual-localized TUFm interacts with PINK1 biochemically and genetically, which is an evolutionarily conserved Parkin-independent route toward mitophagy. A PINK1-dependent TUFm phosphoswitch at Ser222 determines conversion from activating to suppressing mitophagy. PINK1 modulates differential translocation of TUFm because p-S222-TUFm is restricted predominantly to the cytosol, where it inhibits mitophagy by impeding Atg5-Atg12 formation. The self-antagonizing feature of PINK1/TUFm is critical for the robustness of mitophagy regulation, achieved by the unique kinetic parameters of p-S222-TUFm, p-S65-ubiquitin, and their common kinase PINK1. Our findings provide new mechanistic insights into mitophagy and mitophagy-associated disorders.

Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.

Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.

Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

Association of spousal violence and women's empowerment status among the rural women of sub-Saharan Africa.

Spousal violence (SV) is a global problem for women and its elimination is one of the prime targets of Sustainable Development Goal-5. Data from the Demographic and Health Surveys of seventeen countries, representing two sub-Saharan Africa (SSA) regions (East and Southern Africa [ESA] and West and Central Africa [WCA]), were used to examine the relationship between all types of SV and women's empowerment status among rural married women aged 15-49 years. Multivariate logistic regression analysis was used to explore adjusted associations, and a relative index of inequality (RII) and slope index of inequality (SII) were used to measure the inequality in experiencing SV by rural women based on their overall empowerment position. Within the period 2015-2019, the reported rate of SV was higher in the ESA (physical SV: 33.55%; sexual SV: 16.96%; any type of SV: 46.14%) than the WCA countries (physical SV: 27.80%; sexual SV: 7.63%; any type of SV: 40.83%), except for emotional SV (WCA: 31.28% vs ESA: 29.35%). In terms of overall empowerment status, rural WCA women were slightly ahead of their counterparts in the ESA region (46.09% and 44.64%, respectively). For both ESA and WCA countries, women who didn't justify violence and who had access to health care (except physical SV in WCA) showed negative but significant association with all types of SV in the adjusted analysis. Conversely, economic empowerment significantly increased the odds of experiencing physical and any type of SV in both regions. The significant risk ratios obtained from RII, for any SV were 0.83 and 1.09, and the ß-coefficients from SII were -0.082 and 0.037 units, respectively, in ESA and WCA. Multi-sectoral microfinance-based intervening programmes and policies should be implemented regionally to empower women, especially in the economic, socio-culture, health care accessibility dimensions, and this will eventually reduce all types of spousal violence in rural SSA.

Socio-economic inequalities in undiagnosed, untreated, and uncontrolled diabetes mellitus in Bangladesh: is there a gender difference?

OBJECTIVES: We aimed to determine: (1) the prevalence and socio-economic distribution of undiagnosed, untreated, and uncontrolled diabetes mellitus (DM); (2) the relationship between socio-economic status (SES) and undiagnosed, untreated, and uncontrolled DM; and (3) if this relationship is mediated by gender. STUDY DESIGN: Cross-sectional nationally representative household-based survey. METHODS: We used data from the Bangladesh Demographic Health Survey from 2017 to 18. Our findings were based on the responses of 12,144 individuals aged 18 years and older. As a measure of SES, we focused on standard of living (hereinafter referred to as wealth). The study's outcome variables were prevalence of total (diagnosed + undiagnosed), undiagnosed, untreated, and uncontrolled DM. We used three regression-based approaches-adjusted odds ratio, relative inequality index, and slope inequality index-to assess different aspects of SES differences in the prevalence of total, undiagnosed, untreated, and uncontrolled DM. We used logistic regression analysis to look at the adjusted association between SES and the outcomes after gender stratification to see whether gender status moderates the association between SES and the targeted outcomes. RESULTS: In our sample analysis, the age-adjusted prevalence of total, undiagnosed, untreated, and uncontrolled DM was 9.1%, 61.4%, 64.7%, and 72.1%, respectively. Females had a higher prevalence of DM and undiagnosed, untreated, and uncontrolled DM than males. When compared to people in the poor SES group, people in the rich and middle SES groups had 2.60 times (95% confidence interval [CI] 2.05-3.29) and 1.47 times (95% CI 1.18-1.83) higher chance of developing DM. When compared to individuals in the poor SES group, those in the rich SES groups were 0.50 (95% CI 0.33-0.77) and 0.55 times (95% CI 0.36-0.85) less likely to have undiagnosed and untreated DM. CONCLUSIONS: In Bangladesh, rich SES groups were more likely than poor SES groups to have DM, whereas poor SES groups with DM were less likely than rich SES groups to be aware of their disease and obtain treatment. The government and other concerned parties are urged by this study to pay more attention to developing suitable policy measures to reduce the risk of DM, particularly among rich SES groups, as well as targeted efforts to screen for and diagnose DM in socio-economically disadvantaged groups.

A Modified Medical Education Research Study Quality Instrument (MMERSQI) developed by Delphi consensus.

BACKGROUND: The Medical Education Research Study Quality Instrument (MERSQI) is widely used to appraise the methodological quality of medical education studies. However, the MERSQI lacks some criteria which could facilitate better quality assessment. The objective of this study is to achieve consensus among experts on: (1) the MERSQI scoring system and the relative importance of each domain (2) modifications of the MERSQI. METHOD: A modified Delphi technique was used to achieve consensus among experts in the field of medical education. The initial item pool contained all items from MERSQI and items added in our previous published work. Each Delphi round comprised a questionnaire and, after the first iteration, an analysis and feedback report. We modified the quality instruments' domains, items and sub-items and re-scored items/domains based on the Delphi panel feedback. RESULTS: A total of 12 experts agreed to participate and were sent the first and second-round questionnaires. First round: 12 returned of which 11 contained analysable responses; second-round: 10 returned analysable responses. We started with seven domains with an initial item pool of 12 items and 38 sub-items. No change in the number of domains or items resulted from the Delphi process; however, the number of sub-items increased from 38 to 43 across the two Delphi rounds. In Delphi-2: eight respondents gave 'study design' the highest weighting while 'setting' was given the lowest weighting by all respondents. There was no change in the domains' average weighting score and ranks between rounds. CONCLUSIONS: The final criteria list and the new domain weighting score of the Modified MERSQI (MMERSQI) was satisfactory to all respondents. We suggest that the MMERSQI, in building on the success of the MERSQI, may help further establish a reference standard of quality measures for many medical education studies.

Parkinson's Disease: Exploring Different Animal Model Systems.

Disease modeling in non-human subjects is an essential part of any clinical research. To gain proper understanding of the etiology and pathophysiology of any disease, experimental models are required to replicate the disease process. Due to the huge diversity in pathophysiology and prognosis in different diseases, animal modeling is customized and specific accordingly. As in other neurodegenerative diseases, Parkinson's disease is a progressive disorder coupled with varying forms of physical and mental disabilities. The pathological hallmarks of Parkinson's disease are associated with the accumulation of misfolded protein called α-synuclein as Lewy body, and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) area affecting the patient's motor activity. Extensive research has already been conducted regarding animal modeling of Parkinson's diseases. These include animal systems with induction of Parkinson's, either pharmacologically or via genetic manipulation. In this review, we will be summarizing and discussing some of the commonly employed Parkinson's disease animal model systems and their applications and limitations.

History of Parkinson's Disease-Associated Gene, Parkin: Research over a Quarter Century in Quest of Finding the Physiological Substrate.

Parkin, the gene responsible for hereditary Parkinson's disease (PD) called "Autosomal Recessive Juvenile Parkinsonism (AR-JP)" was discovered a quarter of a century ago. Owing to its huge gene structure and unique protein functions, parkin has become a subject of interest to those involved in PD research and researchers and clinicians in various fields and is being vigorously studied worldwide in relation to its nature and disease. The gene structure was registered under the gene name "parkin" in the GenBank in 1997. In 1998, deletion and point mutations in the parkin gene were reported, thereby demonstrating parkin is the causative gene for hereditary PD. Although 25 years have passed since the gene's discovery and many researchers have worked tirelessly to elucidate the function of the Parkin protein and the mechanism of its role against neuronal cell death and pathogenesis remain unknown, which raises a major question concerning the current leading hypothesis. In this review, we present the results of related research on the parkin gene in chronological order and discuss unresolved problems concerning its function and pathology as well as new trends in the research conducted to solve them. The relationship between parkin and tumorigenesis has also been addressed from the perspective of Parkin's redox molecule.

ATP13A2 Gene Silencing in Drosophila Affects Autophagic Degradation of A53T Mutant α-Synuclein.

Mutations in ATP13A2 (PARK9), an autophagy-related protein, cause Kufor-Rakeb syndrome, an autosomal recessive, juvenile-onset form of parkinsonism. α-Synuclein (α-syn) is a presynaptic neuronal protein that forms toxic aggregates in Parkinson's disease (PD). We studied α-syn aggregation and autophagic flux in ATP13A2-knockdown Drosophila expressing either wild-type (WT) or mutant α-syn. Dopaminergic (DA) neuron loss was studied by confocal microscopy. Sleep and circadian activity were evaluated in young and old flies using a Drosophila activity monitor. Thirty-day-old ATP13A2-RNAi A53T-α-syn flies had increased Triton-insoluble α-syn levels, compared to control A53T-α-syn flies without ATP13A2-RNAi. Whole-brain staining revealed significantly fewer dopaminergic (DA) neurons in the PPL2 cluster of 30-day-old ATP13A2-RNAi flies expressing WT-, A30P-, and A53T-α-syn than in that of controls. In ATP13A2-RNAi A53T-α-syn flies, autophagic flux was decreased, as indicated by increased accumulation of Ref(2)P, the Drosophila p62 homologue. ATP13A2 silencing decreased total locomotor activity in young, and enhanced sleep features, similar to PD (decreasing bout length), in old flies expressing A53T-α-syn. ATP13A2 silencing also altered the circadian locomotor activity of A30P- and A53T-α-syn flies. Thus, ATP13A2 may play a role in the autophagic degradation of A53T-α-syn.

Parkin Precipitates on Mitochondria via Aggregation and Autoubiquitination.

The loss of the E3 ligase Parkin, in a familial form of Parkinson's disease, is thought to cause the failure of both the polyubiquitination of abnormal mitochondria and the consequent induction of mitophagy, resulting in abnormal mitochondrial accumulation. However, this has not been confirmed in patient autopsy cases or animal models. More recently, the function of Parkin as a redox molecule that directly scavenges hydrogen peroxide has attracted much attention. To determine the role of Parkin as a redox molecule in the mitochondria, we overexpressed various combinations of Parkin, along with its substrates FAF1, PINK1, and ubiquitin in cell culture systems. Here, we observed that the E3 Parkin monomer was surprisingly not recruited to abnormal mitochondria but self-aggregated with or without self-ubiquitination into the inner and outer membranes, becoming insoluble. Parkin overexpression alone generated aggregates without self-ubiquitination, but it activated autophagy. These results suggest that for damaged mitochondria, the polyubiquitination of Parkin substrates on the mitochondria is not indispensable for mitophagy.

Fast and Sensitive Bioanalytical Method for the Determination of Deucravacitinib in Human Plasma Using HPLC-MS/MS: Application and Greenness Evaluation.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to analyze DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The extract was then subjected to the chromatographic system separation using the ACE-C18 column (4.6 × 100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min-1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in multiple reaction monitoring (MRM) mode. The ion transitions m/z 426.3 → 358.2 were used for DEU quantitation, while the ion transitions m/z 291.1 → 261.1 were used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 and 601.050 ng/mL, utilizing a weighting factor of 1/x2.

Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors.

The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds 27, 29, 30, 33, 37, 38, and 41 were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus pyogenes) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Most of the compounds either had a higher potency than chloramphenicol or an equivalent potency to ciprofloxacin. Compounds 29 and 33 were effective against all the bacterial and fungal strains. Finally, the 1,2,3,4-tetrahydropyrimidine-2-thiol derivatives with a 6-chloro-2-(chloromethyl)-1H-benzo[d]imidazole moiety are potent enough to be considered a promising lead for the discovery of an effective antibacterial agent.

Effect of prepartum dietary energy sources on productive and reproductive performance in Nili Ravi buffaloes.

Feeding of dietary energy sources has been extensively studied in dairy cows but not well described in dairy buffaloes. The objective of this study was to evaluate the effect of prepartum dietary energy sources on productive and reproductive performance in Nili Ravi buffaloes (n = 21). The buffaloes were offered isocaloric (1.55 Mcal/kg DM NEL (net energy for lactation)) glucogenic (GD), lipogenic (LD), and mixed diet (MD) during 63 days prepartum and maintained (1.27 Mcal/kg DM NEL) at lactation diet (LCD) during 14 weeks postpartum. Effects of dietary energy sources and week on animals were analyzed with the mixed model. The DMI, BCS, and body weights remained similar during the pre- and postpartum periods. The prepartum diets did not affect birth weight, blood metabolites, milk yield, and composition. The GD tended to early uterine involution, more follicle numbers, and early follicle formation. The prepartum feeding of dietary energy source had a similar effect on first estrus expression, days open, conception rate, pregnancy rate, and calving interval. So, it could be concluded that prepartum feeding of an isocaloric dietary energy source had a similar effect on the performance of buffaloes.

Does dropout from school matter in taking antenatal care visits among women in Bangladesh? An application of marginalized poisson-poisson mixture model.

BACKGROUND: There exists a lack of research in explaining the link between dropout from school and antenatal care (ANC) visits of women during pregnancy in Bangladesh. The aim of this study is to investigate how the drop out from school influences the ANC visits after controlling the relevant covariates using an appropriate count regression model. METHODS: The association between the explanatory variables and the outcome of interest, ANC visits, have been performed using one-way analysis of variance/independent sample t-test. To examine the adjusted effects of covariates on the marginal mean of count data, Marginalized Poison-Poisson mixture regression model has been fitted. RESULTS: The estimated incidence rate of antenatal care visits was 10.6% lower for the mothers who were not continued their education after marriage but had at least 10 years of schooling (p-value <0.01) and 20.2% lower for the drop-outed mothers (p-value <0.01) than the mothers who got continued their education after marriage. CONCLUSIONS: To ensure the WHO recommended 8+ ANC visits for the pregnant women of Bangladesh, it is essential to promote maternal education so that at least ten years of schooling should be completed by a woman and dropout from school after marriage should be prevented.

Link between unmet need and economic status in Bangladesh: gap in urban and rural areas.

BACKGROUND: Unmet need for family planning (FP) is a core concept in designing FP programmes and reduction of unmet need for FP can improve reproductive and maternal health services. Bangladesh is still away from achieving the target regarding unmet need for FP. This study aimed to explore the composite effect of economic status and place of residence on unmet need for FP among currently married women of reproductive age in Bangladesh after controlling the effect of other selected covariates. METHODS: The study used the data extracted from the Bangladesh Demographic and Health Survey (BDHS) 2017-2018, which is a nationally representative survey implemented using a stratified two-stage cluster sample design. A total of 13,031 currently married women of reproductive age were included in the final analysis. Binary logistic regression model has been employed to identify the factors influencing the unmet need for FP. Model-I investigated the effect of composite variable place-wealth on unmet need for FP and Model-II examined the effect of place-wealth on unmet need for FP after adjusting for the effect of other selected covariates. The Odds Ratios with p-values were reported to identify significant covariates. RESULTS: The rate of unmet need for FP was 15.48%. The composite factor of economic status and place of residence had significant influence on unmet need for FP in both models. Generally, rural women were significantly more likely to have unmet need for FP than their urban counterparts. In particular, women from rural areas and belong to rich families had the highest likelihoods of unmet need for FP. The other selected covariates also had significant influence on unmet need for FP. CONCLUSION: This study shows that rural women had higher odds of unmet need for FP than urban women. The healthcare providers and stakeholders should take necessary actions to motivate women to use contraceptive specially the women who are residing in the rural areas.

Soil organic carbon dynamics in the agricultural soils of Bangladesh following more than 20 years of land use intensification.

Soil organic carbon (SOC) is a key soil quality indicator, as it is a source and storage of plant nutrients and plays a vital role in soil fertility and productivity maintenance. Intensification of agriculture is known to cause SOC decline; however, much of the evidence stems from field-scale experimental trials. The primary aim of this study is to investigate how more than 20 years of agricultural land use intensification in Bangladesh has influenced SOC levels at landscape levels. This was achieved by revisiting in 2012 four sub-sites from the Brahmaputra and Ganges alluviums which were previously sampled (1989-92) by the Soil Resource Development Institute and collecting 190 new samples. These were located at different elevations and subjected to differing amounts of inundation. The SOC was determined using the same method, potassium dichromate wet oxidation, used in the 1989-92 campaign. A comparison of the SOC in the 2012 samples with their historic levels (1989-92) revealed that overall SOC declined significantly across both alluviums as well at their four sub-sites. Further analysis, however, showed that SOC has declined more at higher sites. The higher sites are inundated to a limited level, which makes them suitable for growing multiple crops. Among the land types considered here, the low land sites (because of their topographical position) remain inundated for a greater part of the year, allowing a maximum of only one crop of submerged rice. As a result of reduced biomass decomposition due to anaerobic conditions when inundated, and lower land use/cropping intensity, SOC accretion has occurred in the lower land sites. The SOC levels in South Asian countries are inherently low and agricultural land use intensification fuelled by growing food production demand is causing further SOC loss, which has the potential to jeopardise food security and increase the environmental impact of agriculture.

Effects of prepartum dietary protein level and feed intake on postpartum lactation performance and feeding behavior of multiparous Holstein dairy cows.

An experiment was conducted to determine the effects of low and high metabolizable protein (MP) diets when fed for ad libitum and controlled intake during the prepartum period on postpartum lactation performance and feeding behavior of dairy cows. Thirty-six multiparous Holstein cows were blocked by parity, expected calving date, and previous lactation milk yield at -21 d relative to expected calving and were randomly assigned to 1 of 4 close-up period dietary treatments providing low MP (LMP) or high MP (HMP) diets with controlled intake (CNI) or ad libitum intake (ALI). The concentrations of MP were 65 and 90 g/kg dry matter for LMP and HMP diets, respectively, whereas intake was controlled to supply 100 and 160% of the NRC (2001) energy requirements for CNI and ALI groups, respectively. The concentration of net energy for lactation (NEL) in the treatment diets was 1.50 Mcal/kg. All cows were fed a similar lactation diet after calving (1.50 Mcal/kg of NEL and 83.3 g/kg of MP). The HMP diet increased dry matter intake during the first 3 wk and tended to increase dry matter intake over the 9 wk of lactation. Meal size and eating rate increased in the ALI cows during the prepartum period. Meal frequency increased with the HMP diet during the postpartum period. Milk yield increased by 15.2% with the HMP diet over the 9 wk of lactation. The HMP diet increased energy-corrected milk (ECM) yield in CNI versus ALI cows, whereas the LMP diet increased ECM yield in ALI versus CNI cows over the 9 wk of lactation. The increase in ECM yield of LMP-ALI versus LMP-CNI cows was supported by greater body condition loss and serum ß-hydroxybutyrate over the 9 wk of lactation. Taken together, these data indicate that prepartum controlled intake of a high protein diet can provide the benefits of both strategies.

Mobile Apps to Improve Medication Adherence in Cardiovascular Disease: Systematic Review and Meta-analysis.

BACKGROUND: Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes. OBJECTIVE: The objective of this study is to assess the effects of mobile health care apps on medication adherence and health-related outcomes in patients with CVD. This study also evaluates apps' functionality and usability and the involvement of health care professionals in their use. METHODS: Electronic databases (MEDLINE [Ovid], PubMed Central, Cochrane Library, CINAHL Plus, PsycINFO [Ovid], Embase [Ovid], and Google Scholar) were searched for randomized controlled trials (RCTs) to investigate app-based interventions aimed at improving medication adherence in patients with CVD. RCTs published in English from inception to January 2020 were reviewed. The Cochrane risk of bias tool was used to assess the included studies. Meta-analysis was performed for clinical outcomes and medication adherence, with meta-regression analysis used to evaluate the impact of app intervention duration on medication adherence. RESULTS: This study included 16 RCTs published within the last 6 years. In total, 12 RCTs reported medication adherence as the primary outcome, which is the most commonly self-reported adherence. The duration of the interventions ranged from 1 to 12 months, and sample sizes ranged from 24 to 412. Medication adherence rates showed statistically significant improvements in 9 RCTs when compared with the control, and meta-analysis of the 6 RCTs reporting continuous data showed a significant overall effect in favor of the app intervention (mean difference 0.90, 95% CI 0.03-1.78) with a high statistical heterogeneity (I2=93.32%). Moreover, 9 RCTs assessed clinical outcomes and reported an improvement in systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels in the intervention arm. Meta-analysis of these clinical outcomes from 6 RCTs favored app interventions, but none were significant. In the 7 trials evaluating app usability, all were found to be acceptable. There was a great variation in the app characteristics. A total of 10 RCTs involved health care professionals, mainly physicians and nurses, in the app-based interventions. The apps had mixed functionality: 2 used education, 7 delivered reminders, and 7 provided reminders in combination with educational support. CONCLUSIONS: Apps tended to increase medication adherence, but interventions varied widely in design, content, and delivery. Apps have an acceptable degree of usability; yet the app characteristics conferring usability and effectiveness are ill-defined. Future large-scale studies should focus on identifying the essential active components of successful apps. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42019121385; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121385.

Muscle cellularity, growth performance and growth-related gene expression of juvenile climbing perch Anabas testudineus in response to different eggs incubation temperature.

Although indigenous climbing perch (Anabas testudineusis) is a highly valuable species, slow growth pattern during the culture period impeding its commercial success in aquaculture. In many fish species, it has been demonstrated that incubation temperature of eggs influenced the muscle development and growth rates, which persisted throughout the subsequent larval and juvenile phases. Therefore, this study aimed to investigate whether different incubation temperature of eggs prior to hatching can stimulate the muscle development, growth, and growth-related gene expression of the slow-growing indigenous species of climbing perch. The fertilized eggs of A. testudineus from an artificial breeding program were incubated under control temperature of 24 °C (IT24), 26 °C (IT26), 28 °C (IT28), and 30 °C (IT30) in 10L glass aquaria with four replicated units for each temperature treatment. After hatching, the larvae from each incubated temperature were separately reared at ambient temperature for 10 days in aquarium, 20 days in hapas, and the next 42 days in cages, totaling 72 days post-hatching (dph). The hatching rates were found significantly (P < 0.05) higher in IT28 compared to the other incubation temperature treatments. After 72 dph, the growth performances (%length gained, %weight gained and SGR) were found to be significantly highest (P < 0.05) in the IT28, followed by the treatments IT30, IT26, and IT24, respectively. Survival rate (73 ± 1.257%) was also found to be highest in the same treatment. The rate of new muscle fiber formation was identified to be significantly highest (P < 0.05) in IT28 followed by the IT26, IT30 and IT24, respectively. The relative mRNA expression level of GHRH, IGF1, IGF2 and PRL was also significantly highest in the IT28 (P < 0.05) compared to other treatments. Results from the present study clearly suggested that 28 °C is the optimum eggs incubation temperature of the native strain of A. testudineus for its highest growth performances in captive breeding condition.

Ellagic Acid Prevents α-Synuclein Aggregation and Protects SH-SY5Y Cells from Aggregated α-Synuclein-Induced Toxicity via Suppression of Apoptosis and Activation of Autophagy.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopamine neurons and the deposition of misfolded proteins known as Lewy bodies (LBs), which contain α-synuclein (α-syn). The causes and molecular mechanisms of PD are not clearly understood to date. However, misfolded proteins, oxidative stress, and impaired autophagy are believed to play important roles in the pathogenesis of PD. Importantly, α-syn is considered a key player in the development of PD. The present study aimed to assess the role of Ellagic acid (EA), a polyphenol found in many fruits, on α-syn aggregation and toxicity. Using thioflavin and seeding polymerization assays, in addition to electron microscopy, we found that EA could dramatically reduce α-syn aggregation. Moreover, EA significantly mitigated the aggregated α-syn-induced toxicity in SH-SY5Y cells and thus enhanced their viability. Mechanistically, these cytoprotective effects of EA are mediated by the suppression of apoptotic proteins BAX and p53 and a concomitant increase in the anti-apoptotic protein, BCL-2. Interestingly, EA was able to activate autophagy in SH-SY5Y cells, as evidenced by normalized/enhanced expression of LC3-II, p62, and pAKT. Together, our findings suggest that EA may attenuate α-syn toxicity by preventing aggregation and improving viability by restoring autophagy and suppressing apoptosis.