Socio-economic status and pregnancy complications and their impact on antenatal care services provided at home and Upazila health complex.

The stage of pregnancy is crucial for women of reproductive age and their families. However, in low- and middle-income countries like Bangladesh, antenatal and postnatal care are not widely practiced due to various socio-economic factors, such as low education levels, income, age, pregnancy knowledge, and limited healthcare facilities. The objective of this study was to examine the factors associated with antenatal care in two locations in Bangladesh based on the data collected from the Bangladesh Demographic and Health Survey (BDHS) 2017-2018. We explored different variables as explanatory variables related to ANC service. The results showed that most of the respondents were from rural areas, with 77.02% receiving antenatal care at home. Women with secondary education were more likely to receive care at home than those without education. The Chi-square test indicated a positive correlation between antenatal care at home with several variables, whereas, in the case of Upazila health complexes, only three variables showed a positive association. Logistic regression analysis further showed some specific variables such as geographical division, religion, iron intake during pregnancy, and reporting pregnancy complications had a significant impact on ANC at home. In contrast, covariates such as residence, division, and wealth index were significant for antenatal care at Upazila health complexes. The division was a significant covariate in both cases. Interestingly, we observed that mothers who had been informed about the signs of pregnancy complications were 92% more likely to receive antenatal care at home than those who had not experienced pregnancy complications. Conversely, the results revealed that mothers who were unaware of pregnancy complications were 32% more likely to receive antenatal care at home than those who had been informed about complications. This suggests that when women are educated about pregnancy complications, they are more likely to receive more antenatal care. However, Bangladesh's situation is quite different due to a lack of proper education and knowledge of antenatal care services.

MicroRNA-128 suppresses tau phosphorylation and reduces amyloid-beta accumulation by inhibiting the expression of GSK3ß, APPBP2, and mTOR in Alzheimer's disease.

INTRODUCTION AND AIMS: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aß) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aß pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD. In this study, the role of miR-128 in tau and Aß pathology as well as the regulatory mechanism underlying its dysregulation were investigated. METHODS: The effect of miR-128 on tau phosphorylation and Aß accumulation was examined in AD cellular models through miR-128 overexpression and inhibition. The therapeutic potential of miR-128 in AD mouse model was assessed by comparing phenotypes of 5XFAD mice administered with miR-128-expressing AAVs with 5XFAD mice administered with control AAVs. Phenotypes examined included behavior, plaque load, and protein expression. The regulatory factor of miR-128 transcription was identified through luciferase reporter assay and validated by siRNA knockdown and ChIP analysis. RESULTS: Both gain-of-function and loss-of-function studies in AD cellular models reveal that miR-128 represses tau phosphorylation and Aß secretion. Subsequent investigations show that miR-128 directly inhibits the expression of tau phosphorylation kinase GSK3ß and Aß modulators APPBP2 and mTOR. Upregulation of miR-128 in the hippocampus of 5XFAD mice ameliorates learning and memory impairments, decreases plaque deposition, and enhances autophagic flux. We further demonstrated that C/EBPα transactivates MIR128-1 transcription, while both C/EBPα and miR-128 expression are inhibited by Aß. CONCLUSION: Our findings suggest that miR-128 suppresses AD pathogenesis, and could be a promising therapeutic target for AD. We also find a possible mechanism underlying the dysregulation of miR-128 in AD, in which Aß reduces miR-128 expression by inhibiting C/EBPα.

An investigation of the relation between life expectancy & socioeconomic variables using path analysis for Sustainable Development Goals (SDG) in Bangladesh.

In today's world, the key variable for measuring population health is life expectancy (LE). The purpose of this research is to find out how life expectancy is related to other factors and develop a model to account for the predictors that contribute to LE. This study is also conducted to investigate and measure the effect of socioeconomic variables on LE in Bangladesh. In this study, the predictor variables are employment rate, gross national income (GNI), population growth rate, unemployment rate, and age dependency ratio. Path analysis disintegrated bivariate analysis and showed that employment rate, GNI, and age dependency ratio are significantly related to life expectancy, although bivariate analysis showed all variables are significantly related to LE. The maximum values of significant factors, GNI and employment rates, are $1930 and 21.32% happened in 2019, which is positively correlated with life expectancy. Also, the maximum value of the age dependency ratio (81.52%) happened in 1991, whereas the maximum value of the dependent variable LE (72.59 years) happened in 2019. It has been observed that LE, GNI, and employment rates all rise with one another. There exists an adverse relationship between LE and age dependency ratio. Based on comparisons with other highly developed nations, Bangladesh's GNI needs to grow faster than other significant factors to boost life expectancy. We have forecasted variables that were significantly related to LE until 2030 for the purpose of sustainable development goals, especially the 3rd goal.

Cilnidipine and magnesium sulfate supplement ameliorates hyperglycemia, dyslipidemia and inhibits oxidative-stress in fructose-induced diabetic rats.

The study was designed to evaluate the safety and efficacy of cilnidipine (CLN) and Mg-supplementation in fructose-induced diabetic rats. Diabetes was induced into male Wister rats by feeding fructose (10% solution) in drinking water for 8 weeks. Diabetic rats were subjected for the oral administration of CLN1 (1 mg/kg/day) and CLN10 (10 mg/kg/day), and/or methyl cellulose (0.5%) as vehicle for 28 days. After 14 days of CLN treatment, MgSO4 (1%) was added to CLN1 and CLN10 groups for another 14 days. Age-matched healthy rats were used as normal control. After 28 days body weights were measured and organ weight to body ratio was calculated. Serum samples were analysed for fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), uric acid, lipid profiles, tri-iodothyronine (T3) and thyroid stimulating hormone (TSH), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), creatine phosphokinase myocardial-band (CK-MB), creatinine, albumin, electrolytes. Oral glucose tolerance tests (OGTT), liver histopathology and in-vivo antioxidant activities were also performed. The survival rate in diabetic rats was 100% after the oral administration of CLN, Mg-supplement and/or vehicle. A significant reduction in FBS levels and improvement in OGTT were observed in CLN10, CLN1+Mg and CLN10 + Mg groups after 28 days. Further, the treatment ameliorated serum lipid profile, uric acid, and albumin levels. The groups CLN10 and CLN10 + Mg improved HbA1c, liver glycogen, creatinine, T3, TSH levels and electrolytes in diabetic rats. Moreover, liver from CLN10 and CLN10 + Mg groups showed preservation of cellular architecture as evidenced by attenuation of inflammatory markers SGPT, SGOT and CK-MB; and the levels of superoxide dismutase (SOD), catalase (CAT), glutathione, malondialdehyde (MDA), markers of oxidative stress were significantly improved. CLN exerted prominent effects in the amelioration of hyperglycemia, dyslipidemia and reduced hepatic inflammation; and Mg-supplementation might have some beneficial effects on diabetic complications and oxidative stress in fructose-induced diabetic rats.

Exploring the multifunctional role of melatonin in regulating autophagy and sleep to mitigate Alzheimer's disease neuropathology.

Melatonin (MLT) is a neurohormone that is regulated by the circadian clock and plays multifunctional roles in numerous neurodegenerative disorders, such as Alzheimer's disease (AD). AD is the most common form of dementia and is associated with the degradation of axons and synapses resulting in memory loss and cognitive impairment. Despite extensive research, there is still no effective cure or specific treatment to prevent the progression of AD. The pathogenesis of AD involves atrophic alterations in the brain that also result in circadian alterations, sleep disruption, and autophagic dysfunction. In this scenario, MLT and autophagy play a central role in removing the misfolded protein aggregations. MLT also promotes autophagy through inhibiting methamphetamine toxicity to protect against neuronal cell death in AD brain. Besides, MLT plays critical roles as either a pro-autophagic indicator or anti-autophagic regulator depending on the phase of autophagy. MLT also has antioxidant properties that can counteract mitochondrial damage, oxidative stress, and apoptosis. Aging, a major risk factor for AD, can change sleep patterns and sleep quality, and MLT can improve sleep quality through regulating sleep cycles. The primary purpose of this review is to explore the putative mechanisms of the beneficial effects of MLT in AD patients. Furthermore, we also summarize the findings from preclinical and clinical studies on the multifunctional roles of MLT on autophagic regulation, the control of the circadian clock-associated genes, and sleep regulation.

Genetic Diversity of SARS-CoV2 and Environmental Settings: Possible Association with Neurological Disorders.

The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.

Molecular Genetics of Early- and Late-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic factors. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood, with three gene variants such as APP, PSEN1, and PSEN2 leading to the disease. Some common alleles, including APOE, are effectively associated with LOAD identified, but the genetics of LOAD is not clear to date. It has been accounted that about 5-10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and the APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease-triggering genes yet. Although several genes have been identified by using the technology of next-generation sequencing in EOAD families, including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants are identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of the ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetic facets which will assist in understanding the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article, based on current knowledge, represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism that might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

Anti-Neuroinflammatory Potential of Polyphenols by Inhibiting NF-κB to Halt Alzheimer's Disease.

Alzheimer's disease (AD) is an irrevocable chronic brain disorder featured by neuronal loss, microglial accumulation, and progressive cognitive impairment. The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies have been found yet. Over the last few decades, research on AD has mainly highlighted pathomechanisms linked to a couple of the major pathological hallmarks, including extracellular senile plaques made of amyloid-ß (Aß) peptides, and intracellular neurofibrillary tangles (NFTs) made of tau proteins. Aß can induce apoptosis, trigger an inflammatory response, and inhibit the synaptic plasticity of the hippocampus, which ultimately contributes to reducing cognitive functions and memory impairment. Recently, a third disease hallmark, the neuroinflammatory reaction that is mediated by cerebral innate immune cells, has become a spotlight in the current research area, assured by pre-clinical, clinical, and genetic investigations. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a cytokine producer, is significantly associated with physiological inflammatory proceedings and thus shows a promising candidate for inflammation- based AD therapy. Recent data reveal that phytochemicals, mainly polyphenol compounds, exhibit potential neuroprotective functions and these may be considered as a vital resource for discovering several drug candidates against AD. Interestingly, phytochemicals can easily interfere with the signaling pathway of NF-κB. This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis.

COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management.

At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no effective treatment of this newly life-threatening and devastating virus. Therefore, it is crucial to search for alternative methods that alleviate or inhibit the spread of COVID-19. In this review, we try to find out the etiology, epidemiology, symptoms as well as transmissions of this novel virus. We also summarize therapeutic interventions and suggest antiviral treatments, immune-enhancing candidates, general supplements, and CoV specific treatments that control replication and reproduction of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

nCOVID-19 Pandemic: From Molecular Pathogenesis to Potential Investigational Therapeutics.

In December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related epidemic was first observed in Wuhan, China. In 2020, owing to the highly infectious and deadly nature of the virus, this widespread novel coronavirus disease 2019 (nCOVID-19) became a worldwide pandemic. Studies have revealed that various environmental factors including temperature, humidity, and air pollution may also affect the transmission pattern of COVID-19. Unfortunately, still, there is no specific drug that has been validated in large-scale studies to treat patients with confirmed nCOVID-19. However, remdesivir, an inhibitor of RNA-dependent RNA polymerase (RdRp), has appeared as an auspicious antiviral drug. Currently, a large-scale study on remdesivir (i.e., 200 mg on first day, then 100 mg once/day) is ongoing to evaluate its clinical efficacy to treat nCOVID-19. Good antiviral activity against SARS-CoV-2 was not observed with the use of lopinavir/ritonavir (LPV/r). Nonetheless, the combination of umifenovir and LPV/r was found to have better antiviral activity. Furthermore, a combination of hydroxychloroquine (i.e., 200 mg 3 times/day) and azithromycin (i.e., 500 mg on first day, then 250 mg/day from day 2-5) also exhibited good activity. Currently, there are also ongoing studies to evaluate the efficacy of teicoplanin and monoclonal and polyclonal antibodies against SARS-CoV-2. Thus, in this article, we have analyzed the genetic diversity and molecular pathogenesis of nCOVID-19. We also present possible therapeutic options for nCOVID-19 patients.

Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration.

Neurodegeneration is the progressive loss of neuronal structures and functions that lead to copious disorders like Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS), and other less recurring diseases. Aging is the prime culprit for most neurodegenerative events. Moreover, the shared pathogenic factors of many neurodegenerative processes are inflammatory responses and oxidative stress (OS). Unfortunately, it is very complicated to treat neurodegeneration and there is no effective remedy. The rapid progression of the neurodegenerative diseases that exacerbate the burden and the concurrent absence of effective treatment strategies force the researchers to investigate more therapeutic approaches that ultimately target the causative factors of the neurodegeneration. Phytochemicals have great potential to exert their neuroprotective effects by targeting various mechanisms, such as OS, neuroinflammation, abnormal protein aggregation, neurotrophic factor deficiency, disruption in mitochondrial function, and apoptosis. Therefore, this review represents the molecular mechanisms of neuroprotection by multifunctional phytochemicals to combat age-linked neurodegenerative disorders.

Melatonin in Alzheimer's Disease: A Latent Endogenous Regulator of Neurogenesis to Mitigate Alzheimer's Neuropathology.

Melatonin, a pineal gland synthesized neurohormone is known as a multifunctioning pleiotropic agent which has a wide range of neuroprotective role in manifold age-related neurodegenerative disorders especially Alzheimer's diseases (AD). AD is a devastating neurodegenerative disorder and common form of dementia which is defined by abnormal and excessive accumulation of several toxic peptides including amyloid ß (Aß) plaques and neurofibrillary tangles (NFTs). The Alzheimer's dementia relates to atrophic changes in the brain resulting in loss of memory, cognitive dysfunction, and impairments of the synapses. Aging, circadian disruption, Aß accumulation, and tau hyperphosphorylation are the utmost risk factor regarding AD pathology. To date, there is no exact treatment against AD progression. In this regard, melatonin plays a crucial role for the inhibition of circadian disruption by controlling clock genes and also attenuates Aß accumulation and tau hyperphosphorylation by regulating glycogen synthase kinase-3 (GSK3) and cyclin-dependent kinase-5 (CDK5) signaling pathway. In this review, we highlight the possible mechanism of AD etiology and how melatonin influences neurogenesis by attenuating circadian disruption, Aß formation, as well as tau hyperphosphorylation. Furthermore, we also find out and summarize the neuroprotective roles of melatonin by the blockage of Aß production, Aß oligomerization and fibrillation, tau hyperphosphorylation, synaptic dysfunction, oxidative stress, and neuronal death during AD progression.

Spectrum of Disease and Prescription Pattern for Outpatients with Neurological Disorders: An Empirical Pilot Study in Bangladesh.

BACKGROUND: Neurological disorders represent one of the most prominent causes of morbidity and mortality that adversely affect the lifestyle of patients and a major percentage of these diseases exists in developing countries. PURPOSE: The objective of this study was to examine the prevalence and prescription pattern for outpatients with neurological disorders in Bangladesh. METHODS: The study was conducted on 1,684 patients in 6 hospitals (National Institute of Neurosciences and Hospital, Dhaka Medical College and Hospital, Bangabandhu Sheikh Mujib Medical University, Shaheed Suhrawardy Medical College, Sir Salimullah Medical College, and Apollo Hospitals Dhaka) of the Dhaka City from March 2014 to June 2015. Data were collected through a predesigned questionnaire from the patients that contain information about gender, age, marital status, occupation, residential status, affected disease, self-medicated medicines, and prescribed medicines. RESULTS: Out of 1,684 patients, 28.38% patients were aged 51-60 years and male, 57.19% predominance. The study exposed headache and migraine for 29.75% patients, followed by stroke for 23.93% patients and seizure for 7.07% patients. Genetic reason for the neurological disorders was seen only among 12.35% patients. In this study, 16.98% patients had been affected by neurological disorders for more than 2 years and 19% of patients for less than 6 months. Most extensively prescribed medicines were multivitamins and multiminerals used by 17.89% of patients followed by nonsteroidal anti-inflammatory drugs and other analgesic by 14.84%; afterwards antiulcerants were used by 12.62%, subsequently anticoagulants were used by 11.61% followed by antihyperlipidemic medicines by 10.26% and antiepileptic drugs by 8.08% of patients. The crucial reasons for the selection of prescribed medicines were the confidence that patients had with the physician's prescribed medicines, which was shown for 40.97% patients and knowledge of the medicines was reported for 35.04% patients. The period of prescribed medicine usage was 1-3 months for 39.73% patients and 3-6 months for 29.16% patients. The patient's compliance for prescribed medicines was satisfactory for 34.56% patients, good for 28.15% patients, and side effects were reported for 23.22% patients. CONCLUSION: In Bangladesh, it is not surprising to note that neurological diseases are more prevalent than other different diseases among different age groups and genders. Headache and migraine, stroke and seizure are most frequently encountered neurological disorders here. Treatment procedure of these disorders is not quite suitable due to the anomalies of health care management systems. Appropriate management of the health care system, especially the placement of hospital and community pharmacy can overcome the existing inconsistencies as well as increase the knowledge, awareness, and perception of the patients about health and neurological disorders.