Genomic characterisation of Escherichia coli isolated from poultry at retail through Sink Surveillance in Dhaka, Bangladesh reveals high levels of multi-drug resistance.

The surveillance of antimicrobial resistance (AMR) in commensal Escherichia coli from livestock at slaughter is widely employed to assess the potential for risk to humans. There is currently a limited understanding of AMR in Bangladesh poultry at retail in live bird markets, with studies focussing solely on phenotypic characterisation of resistance. To address this evidence gap we performed antimicrobial susceptibility testing and whole genome sequencing on E. coli obtained from chickens from live bird markets in Dhaka in 2018 (n = 38) and 2020 (n = 45). E. coli were isolated from caeca samples following ISO guidelines and sequenced using short and long read methods. Multidrug resistance was extremely common (n = 77) and there was excellent concordance between AMR phenotype and the presence of corresponding AMR genes or mutations. There was considerable genomic diversity, with 43 different sequence types detected. Public health considerations included the high occurrence of resistance to ciprofloxacin (n = 75) associated with plasmid-residing qnrS or mutations in the gyrA and parC chromosomal genes; and the detection of a tigecycline resistant isolate harbouring tet(X4) on an IncHI1A/B-IncFIA mosaic plasmid. Thirty-nine isolates were resistant to azithromycin and harboured mphA, with a significant increase in the incidence of resistance between 2018 and 2020. Although azithromycin is banned for veterinary use in Bangladesh it remains an important treatment option for humans. Interestingly, mphA confers high-level resistance to azithromycin and erythromycin, and the latter is commonly used on poultry farms in Bangladesh. Seven isolates were colistin resistant and carried mcr1. For two isolates hybrid assemblies revealed that mcr1 resided on a highly conserved IncHI2 plasmid that had 93% nucleotide identity to a plasmid from the published genome of an E. coli isolate of Bangladeshi human origin. Six isolates had resistance to third generation cephalosporins, associated with plasmid-residing bla CTX-M-55, bla CTX-M-65, or bla DHA-1. By employing phenotypic and genomic approaches for AMR surveillance we have provided new insights into the potential for One Health AMR linkages in Bangladesh. Employing similar approaches in human and environmental sectors will help inform the One Health approach to addressing AMR, and generate evidence to support mitigation measures such as improved antimicrobial stewardship.

Peeling back the many layers of competitive exclusion.

Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard®) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log10Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities' response to Salmonella in chickens with low (≤5.85 Log10 genomes/g) or high (≥6.00 Log10 genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella's SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community's stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.

Therapeutic potential of clinically proven natural products in the management of dementia.

Dementia is a common neurodegenerative disorder connected to damage to nerve cells in the brain. Although some conventional drugs are available for dementia treatments and are still sanctified for dementia patients, their short- and long-term side effects and other limitations make treating patients more challenging. The authors aimed to explain novel options for treating dementia with natural products and unravel some clinically proven natural products. This article systematically reviewed recent studies that have investigated the role of natural products and their bioactive compounds for dementia. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter.In this review, we provide mechanistic insights of clinically validated natural products, including like- Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnier, Omega-3, Tramiprostate and Palmitoylethanolamide with which have therapeutic efficacy against dementia in the management of dementia. As shown by studies, certain natural ingredients could be used to treat and prevent dementia. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against dementia with lesser side effects as compared to currently available treatments. Moreover, these products should be studied further in order to develop novel dementia medications.

Reproductive, maternal, newborn, and child health intervention coverage in 70 low-income and middle-income countries, 2000-30: trends, projections, and inequities.

BACKGROUND: Monitoring the progress in reproductive, maternal, newborn, and child health (RMNCH) using the composite coverage index (CCI) is crucial to evaluate the advancement of low-income and middle-income countries (LMICs) towards the attainment of Sustainable Development Goal target 3. We present current benchmarking for 70 LMICs, forecasting to 2030, and an analysis of inequities within and across countries. METHODS: In this cross-sectional secondary data analysis, we extracted 291 data points from the WHO Equity Monitor, and Demographic and Health Survey Statcompiler for 70 LMICs. We selected countries on the basis of whether they belonged to LMICs, had complete information about the predictors between 2000 and 2030, and had at least one data point related to CCI. CCI was calculated on the basis of eight types of RMNCH interventions in four domains, comprising family planning, antenatal care, immunisations, and management of childhood illnesses. This study examined CCI as the main outcome variable. Bayesian hierarchical models were used to estimate trends and projections of the CCI at regional and national levels, as well as the area of residence, educational level, and wealth quintile. FINDINGS: Despite progress, only 18 countries are projected to reach the 80% CCI target by 2030. Regionally, CCI is projected to increase in all regions of Asia (in southern Asia from 51·8% in 2000 to 89·2% in 2030; in southeastern Asia from 58·8% to 84·4%; in central Asia from 70·3% to 87·0%; in eastern Asia from 76·8% to 82·1%; and in western Asia from 56·5% to 72·1%), Africa (in sub-Saharan Africa from 46·3% in 2000 to 72·2% in 2030 and in northern Africa from 55·0% to 81·7%), and Latin America and the Caribbean (from 67·0% in 2000 to 83·4% in 2030). By contrast, southern Europe is predicted to experience a decline in CCI over the same period (70·1% in 2000 to 55·2% in 2030). Across LMICs, CCIs are higher in urban areas, in populations in which women have higher education levels, and in populations with a high income. INTERPRETATION: Governments of countries where the universal target of 80% CCI has not yet been reached must develop evidence-based policies aimed at enhancing RMNCH coverage. Additionally, they should focus on reducing the extent of existing inequalities within their populations to drive progress in RMNCH. FUNDING: Hitotsubashi University and Japan Society for the Promotion of Science.

Complete genome sequences of bacteria isolated from cockroaches collected in a Bangladeshi hospital.

We report the complete genome sequences of four bacterial strains that were isolated from Blattella germanica (German cockroaches) that were found in three wards of the Rajshahi Medical College Hospital. Multiple antibiotic resistance genes were identified in each genome, with one genome containing multiple plasmid-encoded resistance genes.

A systematic analysis and future projections of the nutritional status and interpretation of its drivers among school-aged children in South-East Asian countries.

Background: Nutrition inadequacy during childhood and adolescence can cause suboptimal growth, intergenerational effects on offspring and an increased risk of chronic diseases in adulthood. There is little information on the prevalence and drivers of malnutrition in children aged 5-19 years, in the South-East Asian setting, since most existing interventions have to date targeted undernutrition. We assessed the national prevalence of nutritional indicators, their trends, and associated risk factors among children aged 5-19 years from 11 countries of WHO South-East Asia Region (SEA Region) in order to provide evidence to guide future policy direction. Methods: We included 5,210,646 children for analysis from 345 studies and 25 survey datasets. A Newcastle-Ottawa Scale was used to assess the quality of the study. Bayesian regression models were used to estimate the prevalence of malnutrition between 2000 and 2030, and a series of subgroup analyses were performed to assess variation in pooled estimates by different socio-demographic and lifestyle factors. The protocol was registered with PROSPERO database (CRD42023400104). Findings: Overall, pooled analysis demonstrated that indicators of undernutrition in SEA is predicted to decrease between 2000 and 2030 including stunting (36.6%-27.2%), thinness (29.5%-6.2%), and underweight (29.2%-15.9%). However, a substantial increase in prevalence of overweight (6.0% in 2000-16.9% in 2030), and obesity (2.6%-9.5%) are predicted. The prevalence of micronutrient deficiencies between 2000 and 2030 is predicted to decrease-vitamin A by 84% and vitamin D by 53%. Parents' education levels and household wealth were inversely associated with malnutrition. Children's health-related behaviours, such as unhealthy dietary habits and spending more time watching TV, playing games, or using the computer, were associated with increased chance of overweight and obesity. There were no clear signs of publication bias in our study. Interpretation: Our analysis highlights the pattern of a double burden of malnutrition, with clear differences between different socio-demographic groups. Despite a substantial reduction in the prevalence of stunting, underweight, and anaemia since 2000, an emerging increase in overweight/obesity and micronutrient deficiencies warrants urgent attention. Funding: World Health Organization Regional Office for South-East Asia New Delhi, India.

Evaluation of Population-Level Tobacco Control Interventions and Health Outcomes: A Systematic Review and Meta-Analysis.

Importance: Smoking causes considerable noncommunicable diseases, perinatal morbidity, and mortality. Objective: To investigate the associations of population-level tobacco-control policies with health outcomes. Data Sources: PubMed, EMBASE, Web of Science, Cumulated Index to Nursing and Allied Health Literature, and EconLit were searched from inception to March 2021 (updated on 1 March 2022). References were manually searched. Study Selection: Studies reporting on associations of population-level tobacco control policies with health-related outcomes were included. Data were analyzed from May to July 2022. Data Extraction and Synthesis: Data were extracted by 1 investigator and cross-checked by a second investigator. Analyses were conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: The primary outcomes were respiratory system disease (RSD), cardiovascular disease (CVD), cancer, mortality, hospitalization, and health care utilization. The secondary outcomes were adverse birth outcomes, such as low birth weight and preterm birth. Random-effects meta-analysis was used to estimate pooled odds ratios (ORs) and 95% CIs. Results: Of 4952 records identified, 144 population-level studies were included in the final analysis; 126 studies (87.5%) were of high or moderate quality. The most frequently reported policies were smoke-free legislation (126 studies), followed by tax or price increases (14 studies), multicomponent tobacco control programs (12 studies), and a minimum cigarette purchase age law (1 study). Smoke-free legislation was associated with decreased risk of all CVD events (OR, 0.90; 95% CI, 0.86-0.94), RSD events (OR, 0.83; 95% CI, 0.72-0.96), hospitalization due to CVD or RSD (OR, 0.91; 95% CI, 0.87-0.95), and adverse birth outcomes (OR, 0.94; 95% CI, 0.92-0.96). These associations persisted in all sensitivity and subgroup analyses, except for the country income category, for which a significant reduction was only observed in high-income countries. In meta-analysis, there was no clear association of tax or price increases with adverse health outcomes. However, for the narrative synthesis, all 8 studies reported statistically significant associations between tax increases and decreases in adverse health events. Conclusions and Relevance: In this systematic review and meta-analysis, smoke-free legislation was associated with significant reductions in morbidity and mortality related to CVD, RSD, and perinatal outcomes. These findings support the need to accelerate the implementation of smoke-free laws to protect populations against smoking-related harm.

The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito.

Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence-but coming at the cost of optimal replication in humans-and may represent a first step towards a future emergence event.

Stem Cell Therapy in Diabetic Polyneuropathy: Recent Advancements and Future Directions.

Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for DPN. Under these circumstances, cell therapy may be a vital candidate for the treatment of DPN. The epidemiology, classification, and treatment options for DPN are disclosed in the current review. Cell-based therapies using bone marrow-derived cells, embryonic stem cells, pluripotent stem cells, endothelial progenitor cells, mesenchymal stem cells, or dental pulp stem cells are our primary concern, which may be a useful treatment option to ease or to stop the progression of DPN. The importance of cryotherapies for treating DPN has been observed in several studies. These findings may help for the future researchers to establish more focused, accurate, effective, alternative, and safe therapy to reduce DPN. Cell-based therapy might be a permanent solution in the treatment and management of diabetes-induced neuropathy.

Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis Among Japanese Workers.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. METHODS: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. RESULTS: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. CONCLUSION: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Unveiling the Potential of Polyphenols as Anti-Amyloid Molecules in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aß) cascade is the dominant hypothesis. According to the Aß hypothesis, a progressive buildup of extracellular and intracellular Aß aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aß plays an important role in the etiology of AD, therefore Aß-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aß plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aß (a peptide of 39-42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aß aggregation and prevent the formation of Aß oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aß in AD pathogenesis, the Aß aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.

A systematic review and meta-analysis of unmet needs for healthcare and long-term care among older people.

BACKGROUND: The absolute number of older individuals needing medical care and long-term care (LTC) is increasing globally due to the growing ageing population. However, it is uncertain who and what proportion of the population has access to care. Therefore, a systematic review and meta-analysis of the prevalence and reasons for unmet needs for healthcare and long-term care among older people, 65 years old and above, across countries was conducted. METHODS: An information specialist performed a comprehensive search of four major databases (PubMed, EMBASE, Web of Science, and CINAHL) from inception to June 2020 without restrictions on language and date. We did random-effects meta-analysis to obtain pooled prevalence. We stratified the meta-analysis by reasons for unmet need categorized by barrier dimension (availability, accessibility, affordability, and acceptability), survey year, geographic location, and socio-demographic characteristics of the older individual. RESULTS: After screening 3912 articles, we included 101 studies published between 1996 and 2020. Of the 101 studies, 87 studies reported unmet healthcare needs and 14 studies reported unmet LTC needs. Overall, 10.4% (95% CI, 7.3-13.9) of the older population had unmet needs for healthcare. The common reasons for unmet healthcare needs were cost of treatment, lack of health facilities, lack of/conflicting time, health problem not viewed as serious, and mistrust/fear of provider. A significant variation in pooled prevalence of unmet healthcare needs due to cost was found by gender (male [10.9, 95% CI, 8.9-13.1] vs female [14.4, 95% CI, 11.8-17.3]), educational level (primary or less [13.3, 95% CI, 9.6-17.6] vs higher [7.5, 95% CI, 5.9-9.3]), self-reported health (poor [23.2, 95% CI, 18.8-27.8] vs good [4.4, 95% CI, 3.4-5.5]), insurance status (insured [9.0, 95% CI, 7.5-10.6] vs uninsured [27.7, 95% CI, 24.0-31.5]), and economic status of population (poorest [28.2, 95% CI, 14.1-44.9] vs richest [7.1, 95% CI, 3.8-11.3]). One in four (25.1, 95% CI, 17.1-34.2) older people had unmet needs in LTC. Rural residents had a higher prevalence of unmet needs in LTC compared to their urban counterparts. CONCLUSION: With the population ageing globally, it is necessary to improve access to health care and LTC for older people. Ensuring affordability of health services, reducing geographical barriers, and improving acceptability, will be critical in reducing unmet need. Unmet needs for healthcare were concentrated in population with no education, poor economic group, outpatient health facility user, and uninsured group. With education and economic-based inequalities at the forefront, all countries should focus on improving access to health services by reducing the burden related to healthcare costs.

Equity in access to safely managed sanitation and prevalence of diarrheal diseases in Bangladesh: a national and sub-national analysis.

BACKGROUND: In Bangladesh, safely managed sanitation (SMS) coverage is low, and diarrheal disease is a significant health problem. This study estimated the inequality in access to SMS facilities at the national and sub-national levels and assessed the prevalence of diarrheal diseases in connection with these improved facilities. METHODS: Data were extracted from the Bangladesh Demographic and Health Survey, conducted during 2017-2018. SMS was defined as using an improved sanitation facility, which designed to hygienically separate excreta from human contact and include the use of a flush toilet connected to piped sewer system, septic tank, ventilated improved pit latrine, pit latrine with a slab, and composting toilet. The slope index of inequality (SII) and multi-level regression models were used for inequality and risk factors of SMS respectively. RESULTS: The national coverage of SMS was 44.0% (45.3% and 43.5% in urban and rural areas, respectively). At the sub-national level, the lowest and highest coverage of SMS was observed in Mymensingh (32.9%) and Chittagong (54.1%) divisions, respectively. The national level SII indicated that wealthy households had access to higher SMS by 60.8 percentage points than poor households. Additionally, greater inequality was observed in rural areas, which was 71.9 percentage points higher in the richest households than in the poorest households. The coverage gap between the rich and poor was highest in the Sylhet division (85.3 percentage points higher in rich than in poor) and lowest in Dhaka (34.9 percentage points). Old and highly educated household heads and richest households had better access to higher levels of adequate sanitation. After adjusting for confounding variables, the prevalence of diarrheal disease was 14.0% lower in the SMS user group than in their counterparts. CONCLUSION: Substantial inequalities in access to SMS exist at both national and sub-national levels of Bangladesh, with the prevalence of diarrhea being lower among SMS users. These findings may help to prioritize resources for reducing inequality and expanding the coverage of improved sanitation in Bangladesh.

Recent advances and limitations of mTOR inhibitors in the treatment of cancer.

The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.

Global, regional, and national progress in financial risk protection towards universal health coverage, 2000-2030.

INTRODUCTION: Complete (100%) protection against catastrophic health expenditure (CHE) and impoverishment is the main target of universal health coverage (UHC). Evidence-based estimates must be at the heart of policy development for UHC, further research using updated data is essential to monitor, track, and compare country progress up to 2030. We estimate global, regional, and country-level CHE and impoverishment during 2000-2030. METHODS: We aggregated 636 data points from 140 countries that were conducted between 2000 and 2021. We used Bayesian hierarchical model for trend and projection analysis. Furthermore, we constructed scenario-based projections of CHE and impoverishment based on 5% GDP spending on health and per capita health expenditure (PCHE) of $86. RESULTS: Most countries fail to achieve financial protection targets by 2030, with the global incidence of CHE predicted to persist around 7% at 10% threshold. CHE is predicted to increase in most of Asia (Southern: 8.1% in 2000 to 13.4% in 2030; Central: 3.6%-23.2%; Eastern: 8.3%-14.4%; and Western: 7.3%-20.2%), Northern Africa (12.4%-27.2%), Eastern (7.1%-14.9%) and Northern Europe (6.6%-13.2%). In contrast, a decrease is predicted in Oceania, Latin America and the Caribbean, and Northern America. By 2030, incidence of impoverishment is predicted to be 0% worldwide at $3.10 poverty line, however in several African and Soth Asian countries is predicted to be high impoverishment. The scenario-based analysis indicated that CHE and impoverishment is expected to decrease in 41 and 42 countries for GDP increase and 43 and 62 for PCHE increase respectively compared to current spending on health. CONCLUSION: To accelerate progress towards reducing financial protection, governments should carefully assess the country context to determine how health can be prioritised through government spending to reduce out-of-pocket payments.

Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview.

MAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer.

Relationship of chronotype and social jetlag with adherence to the Japanese dietary guidelines among workers.

While late chronotype and greater social jetlag have been associated with poor dietary behavior among the general population, these associations have not been investigated among workers, who struggle to align their sleep timings with work schedules. We aimed to explore the cross-sectional association of social jetlag and a late chronotype with adherence to a healthy diet among Japanese workers. Participants were 1,435 non-shift workers (18-78 years) who attended a nutritional survey. Social jetlag was defined as the difference in the midpoint of sleep times between weekdays and weekends, while chronotype was estimated using the mid-sleep time on weekends that was corrected with sleep debt on weekdays. We calculated the adherence score of the Japanese Food Guide Spinning Top (JFGST) - healthy diet guidelines for Japanese. Multivariable linear regression analyses were used to calculate the adjusted means and 95% confidence intervals (CI) for adherence scores of social jetlag and chronotype. We found that greater social jetlag was associated with a lower JFGST score. The multivariable-adjusted mean (95% CI) of JFGST scores were 39.7 (39.1-40.2), 38.7 (37.9-39.6), and 38.1 (36.6-39.7) for <1 hour, 1 to <2 hours, and ≥2 hours of social jetlag, respectively (P-trend = 0.02). Workers with late chronotypes had significantly lower adherence scores on JFGST [36.3 (34.7-37.8); P-trend = 0.002]. Results suggest that a late chronotype and social jetlag are inversely associated with adherence to a healthy diet among Japanese workers.

AD-CovNet: An exploratory analysis using a hybrid deep learning model to handle data imbalance, predict fatality, and risk factors in Alzheimer's patients with COVID-19.

Alzheimer's disease (AD) is the leading cause of dementia globally, with a growing morbidity burden that may exceed diagnosis and management capabilities. The situation worsens when AD patient fatalities are exposed to COVID-19. Because of differences in clinical features and patient condition, a patient's recovery from COVID-19 with or without AD varies greatly. Thus, this situation stimulates a spectrum of imbalanced data. The inclusion of different features in the class imbalance offers substantial problems for developing of a classification framework. This study proposes a framework to handle class imbalance and select the most suitable and representative datasets for the hybrid model. Under this framework, various state-of-the-art resample techniques were utilized to balance the datasets, and three sets of data were finally selected. We developed a novel hybrid deep learning model AD-CovNet using Long Short-Term Memory (LSTM) and Multi-layer Perceptron (MLP) algorithms that delineate three unique datasets of COVID-19 and AD-COVID-19 patient fatality predictions. This proposed model achieved 97% accuracy, 97% precision, 97% recall, and 97% F1-score for Dataset I; 97% accuracy, 97% precision, 96% recall, and 96% F1-score for Dataset II; and 86% accuracy, 88% precision, 88% recall, and 86% F1-score for Dataset III. In addition, AdaBoost, XGBoost, and Random Forest models were utilized to evaluate the risk factors associated with AD-COVID-19 patients, and the outcome outperformed diagnostic performance. The risk factors predicted by the models showed significant clinical importance and relevance to mortality. Furthermore, the proposed hybrid model's performance was evaluated using a statistical significance test and compared to previously published works. Overall, the uniqueness of the large dataset, the effectiveness of the deep learning architecture, and the accuracy and performance of the hybrid model showcase the first cohesive work that can formulate better predictions and help in clinical decision-making.

A review on machine learning and deep learning for various antenna design applications.

The next generation of wireless communication networks will rely heavily on machine learning and deep learning. In comparison to traditional ground-based systems, the development of various communication-based applications is projected to increase coverage and spectrum efficiency. Machine learning and deep learning can be used to optimize solutions in a variety of applications, including antennas. The latter have grown popular for obtaining effective solutions due to high computational processing, clean data, and large data storage capability. In this research, machine learning and deep learning for various antenna design applications have been discussed in detail. The general concept of machine learning and deep learning is introduced. However, the main focus is on various antenna applications, such as millimeter wave, body-centric, terahertz, satellite, unmanned aerial vehicle, global positioning system, and textiles. The feasibility of antenna applications with respect to conventional methods, acceleration of the antenna design process, reduced number of simulations, and better computational feasibility features are highlighted. Overall, machine learning and deep learning provide satisfactory results for antenna design.

Cognitive and affective disturbances in patients with Parkinson's disease: Perspectives for classifying of motor/neuropsychiatric subtypes.

Parkinson's disease (PD) is a neurological disorder, related to rigidity, bradykinesia, and resting tremors, among other motor symptoms. It is noticed in the increasing frequency of neuropsychiatric disorders, which may be also caused by non-motor symptoms of PD. Treatment of PD is usually based on the classification of motor subtypes; however, it remains unclear whether motor subtypes have differences in the severity of psychiatric symptoms. It determines the importance of discovering possible neuropsychiatric subtypes of PD. We conducted a clinical study, which included group 1 - patients with postural instability and gait disorders dominant (PIGD) subtype, group 2 - patients with tremor dominant (TD) and indeterminate subtypes (non-PIGD), and group 3 - people who did not have CNS damage. We used the Montreal Cognitive Assessment, Russified 20-point version of the Toronto Alexithymia Scale, State-Trait Anxiety Inventory, and Beck Depression Inventory for assessment of the mental status. It was the first time that neuropsychiatric subtypes of PD had been investigated based on the condition of cognition and mood. Cluster analysis gave us the possibility to classify our patients by the following subtype: affective-cognitive PIGD, anxious PIGD, affective-cognitive non-PIGD, and non-PIGD without psychiatric symptoms. This indicates a closed link between psychiatric and motor symptoms, which can be used for the improved treatment of PD.