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BackgroundElevated high-sensitivity cardiac troponin (hs-cTn) levels are linked with cardiovascular disease and cognitive impairment, both of which are strong risk factors for late-life dementia (LLD). This study examined the association between hs-cTnI levels below the sex-specific 99th percentile for myocardial injury and the incidence of LLD in older women.Methods986 community-dwelling women aged ≥70 years without prior LLD and with hs-cTnI <15.6 ng/L (stratified into quartiles) were included from the Perth Longitudinal Study of Ageing Women. The primary outcome was incident LLD events, including LLD hospitalisation or death, over 14.5 years obtained from linked health records. Associations between hs-cTnI and LLD outcomes were explored using multivariable-adjusted Cox models, as part of restricted cubic splines.ResultsAt baseline, participants’ mean (±SD) age was 75.2±2.7 years. Over 14.5 years of follow-up, LLD events (n=174, 17.7%), hospitalisations (n=155, 15.7%) and deaths (n=68, 6.9%) were recorded. Compared with those in the lowest quartile (Q1, median 3.1 ng/L), women in the highest quartile of hs-cTnI (Q4, median 7.3 ng/L) had a greater risk of developing LLD-related events (adjusted HR: 1.88, 95% CI: 1.22 to 2.91), hospitalisation (adjusted HR: 1.65, 95% CI: 1.04 to 2.64) and death (adjusted HR: 2.27, 95% CI: 1.13 to 4.59), after adjusting for established cardiovascular and dementia risk factors, including apolipoprotein E (APOE) genotype.ConclusionAmong older women, hs-cTnI levels below the sex-specific 99th percentile for myocardial injury were associated with an increased risk of LLD events over 14.5 years. These findings suggest that hs-cTnI may identify older women at higher risk of LLD, capturing both cardiovascular and brain health vulnerability in older age.Trial registration numberACTRN12617000640303.

Alzheimer’s disease is a neurodegenerative disease characterized by deposition of extracellular amyloid-β, intracellular neurofibrillary tangles, and loss of cortical neurons. However, the mechanism underlying neurodegeneration in Alzheimer’s disease (AD) remains to be explored. Many of the researches on AD have been primarily focused on neuronal changes. Current research, however, broadens to give emphasis on the importance of nonneuronal cells, such as astrocytes. Astrocytes play fundamental roles in several cerebral functions and their dysfunctions promote neurodegeneration and, eventually, retraction of neuronal synapses, which leads to cognitive deficits found in AD. Astrocytes become reactive as a result of deposition of Aβ, which in turn have detrimental consequences, including decreased glutamate uptake due to reduced expression of uptake transporters, altered energy metabolism, altered ion homeostasis (K+ and Ca+), increased tonic inhibition, and increased release of cytokines and inflammatory mediators. In this review, recent insights on the involvement of, tonic inhibition, astrocytic glutamate transporters and aquaporin in the pathogenesis of Alzheimer’s disease are provided. Compounds which increase expression of GLT1 have showed efficacy for AD in preclinical studies. Tonic inhibition mediated by GABA could also be a promising target and drugs that block the GABA synthesizing enzyme, MAO-B, have shown efficacy. However, there are contradictory evidences on the role of AQP4 in AD.

Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.

Background. Epilepsy is a chronic neurological disorder characterized by unprovoked recurrent seizure episodes. The disease has detrimental effects on social, cognitive, psychological, and physical components of life consequently quality of life of the patients. The level of the effect of the disease on quality life is influenced by different factors including the use of antiepileptic medications. Objectives. The study was aimed at assessing quality of life in patients with epilepsy and the variables affecting it in Mekelle city, northern Ethiopia. Methods. 175 patients with epilepsy aging 18 years old and above attending neurologic clinics of the two governmental hospitals available in Mekelle city were interviewed using standard and validated Tigrigna version of Quality of Life in Epilepsy Scale-31 (QOLIE-31). One-way ANOVA and independent t-test and analysis of covariance were used for data analysis. Result. The mean age of the patients was 29.36 (standard deviation (SD) 12.77) years old, and 61% of them were males while 52% of the respondents were on phenobarbitone monotherapy. The mean total QOLIE-31 score was 77.97 (SD 20.78) with the highest subscale score for medication effects and the lowest for overall quality of life (QOL) functioning with a score of 86.2 (SD 22.12) and 70.97 (SD 26.43), respectively. The patients with high seizure frequency in the past month before the current visit had a significantly low quality of life 76.81 (SD 21.11). Conversely, patients with tertiary education and above had shown a significantly high quality of life 89.52 (SD 11.85). Conclusion. The overall QOL of the patients was good. Seizure frequency and level of education were found significant predictors of QOL showing the necessity of seizure control and patient education for improving quality of life in patients with epilepsy.

ObjectiveTo examine the association between high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, muscle function decline and 14.5-year fall-related hospitalisation risk in women aged over 70 years.Methods1179 ambulatory community-dwelling women aged over 70 years with subclinical levels of hs-cTnI (ie, <15.6 ng/L), who were followed up for 14.5 years, were included. Samples for hs-cTnI were obtained in 1998. Fall-related hospitalisations were retrieved from linked health records. Muscle function measures, including handgrip strength and the Timed-Up-and-Go (TUG) test, were assessed in 1998 and 2003.ResultsMean±SD age was 75.2±2.7 years. Over 14.5 years of follow-up, 40.4% (476 of 1179) experienced fall-related hospitalisation. Participants were categorised into four approximate hs-cTnI quartiles: quartile 1 (<3.6 ng/L), quartile 2 (3.6–4.4 ng/L), quartile 3 (4.5–5.8 ng/L) and quartile 4 (≥5.9 ng/L). Compared with those in Q1, women in Q4 were likely to experience fall-related hospitalisation (36.0% vs 42.8%). In a multivariable-adjusted model that accounted for CVD and fall risk factors, compared with women in Q1, those in Q4 had a 46% higher risk of fall-related hospitalisation (HR 1.46, 95% CI 1.08 to 1.98). Additionally, women in Q4 had slower TUG performance compared with those in Q1 (10.3 s vs 9.5 s, p=0.032).ConclusionElevated level of hs-cTnI was associated with slower TUG performance and increased fall-related hospitalisation risk. This indicates subclinical level of hs-cTnI can identify clinically relevant falls, emphasising the need to consider cardiac health during fall assessment in women aged over 70 years.Trial registration numberACTRN12617000640303.

ObjectiveInappropriate use of medicine is a global challenge with greater impact on developing countries. Assessment of drug use pattern is used to identify gaps in medicine utilisation to implement strategies for promoting rational drug use. This study aimed to assess drug use pattern using the WHO drug use indicators in selected general hospitals in Tigray region, Ethiopia.DesignA cross-sectional study was conducted using WHO drug use indicators in two public hospitals located in Tigray.SettingPrescriptions recorded from 1 January 2017 to 1 June 2019 were randomly selected, and participants who visited the public hospitals from 1 March 2019 to 30 August 2019 and hospital pharmacies were interviewed.Participants100 patients who visited both outpatient clinics and hospital pharmacy departments of the public hospitals.ResultsThe average number of medicines per prescription was 1.69 (±0.81). Prescriptions containing antibiotics and injectables were 58.2% and 15.9%, respectively. The percentages of medicines prescribed with a generic name from essential medicines list of Ethiopia were 97.5% (974) and 88.1% (970) in Mekelle Hospital and Quiha Hospital, respectively. The patients spent an average of 6.6(±3.5) min with their general practitioners, while only 22.8 (±21.7) s with their pharmacists. Of the patients interviewed, 56.9% knew their dosing regimen and 32.7% of them had their medication labelled.ConclusionThe finding of the present study revealed deviation of drug use pattern from the WHO optimal levels suggesting the hospitals had limitations in appropriate utilisation of medicines. Understanding the factors attributed to the observed gaps and implementing corrective measures are required to conform with the recommended standards of appropriate drug utilisation.

Background. Malaria remains a major public health problem globally. Poor access to antimalarial drugs compounded with rapidly evolving drug resistance encourages researchers to continuously look for new drugs. Of importance, traditionally used medicines of plant origin are the highest priority as the ethnobotanical claim can be used as an important clue for its safety and efficacy profiles. Silene macrosolen A. Rich (Caryophyllaceae) has been traditionally used for malaria treatment in Ethiopia. Therefore, this study was aimed to evaluate the in vivo antimalarial activity of the plant against Plasmodium-berghei-infected (ANKA strain) Swiss albino mice. Methods. The dried powdered root of Silene macrosolen was extracted using 80% methanol. The crude extract was fractionated using chloroform, ethyl acetate, and distilled water that have different affinities to plant phytoconstituents. The in vivo antimalarial activities of the crude extract were evaluated using 4-day suppressive, prophylactic, and curative tests. The antimalarial activity of the solvent fractions was evaluated in a 4-day suppressive test. The oral acute toxicity of the crude extract was also determined according to the OECD guidelines. Results. The percentage of parasite suppression on the crude extract was 31.02%, 35.82%, and 39.23% in prophylactic, curative, and 4-day suppressive tests, respectively, at the tested dose level of 400 mg/kg. The percentages of chemosuppression of the solvent fractions (400 mg/kg) were 43.07%, 42.61%, and 38.38% in aqueous, ethyl acetate, and chloroform fractions, respectively. Both the crude extract and solvent fractions also significantly prolonged survival time except in the prophylactic test. In addition, prevention of weight loss and reduction in temperature and packed cell volume (PCV) were observed in crude extract as well as solvent fractions. The acute toxicity test of the plant extract also exhibited no sign of toxicity. Conclusion. The result indicated that Silene macrosolen has a significant antimalarial activity, justifying the traditional use of the plant material for treatment of malaria.

Background. Epilepsy is one of the common neurological illnesses which affects millions of individuals globally. Although the majority of epileptic patients have a good response for the currently available antiepileptic drugs (AEDs), about 30-40% of epileptic patients are developing resistance. In addition to low safety profiles of most of existing AEDs, there is no AED available for curative or disease-modifying actions for epilepsy so far. Objectives. This systematic review is intended to evaluate the effect of metformin in acute and chronic animal models of an epileptic seizure. Methods. We searched PubMed, SCOPUS, Sciences Direct, and grey literature in order to explore articles published in English from January 2010 to November 2018, using key terms “epilepsy,” “seizure,” “metformin,” “oral hypoglycemic agents,” and “oral antidiabetic drugs”. The qualities of all the included articles were assessed according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES). Results. Out of six hundred fifty original articles retrieved, eleven of them fulfilled the inclusion criteria and were included for final qualitative analysis. In these studies, metformin showed to control seizure attacks by attenuating seizure generation, delaying the onset of epilepsy, reducing hippocampal neuronal loss, and averting cognitive impairments in both acute and chronic models of an epileptic seizure. The possible mechanisms for its antiseizure or antiepileptic action might be due to activation of AMPK, antiapoptotic, antineuroinflammatory, and antioxidant properties, which possibly modify disease progression through affecting epileptogenesis. Conclusion. This review revealed the benefits of metformin in alleviating symptoms of epileptic seizure and modifying different cellular and molecular changes that affect the natural history of the disease in addition to its good safety profile.

ObjectiveThe aim of this study was to provide a comprehensive evidence on risk factors for transmission, disease severity and COVID-19 related deaths in Africa.DesignA systematic review has been conducted to synthesise existing evidence on risk factors affecting COVID-19 outcomes across Africa.Data sourcesData were systematically searched from MEDLINE, Scopus, MedRxiv and BioRxiv.Eligibility criteriaStudies for review were included if they were published in English and reported at least one risk factor and/or one health outcome. We included all relevant literature published up until 11 August 2020.Data extraction and synthesisWe performed a systematic narrative synthesis to describe the available studies for each outcome. Data were extracted using a standardised Joanna Briggs Institute data extraction form.ResultsFifteen articles met the inclusion criteria of which four were exclusively on Africa and the remaining 11 papers had a global focus with some data from Africa. Higher rates of infection in Africa are associated with high population density, urbanisation, transport connectivity, high volume of tourism and international trade, and high level of economic and political openness. Limited or poor access to healthcare are also associated with higher COVID-19 infection rates. Older people and individuals with chronic conditions such as HIV, tuberculosis and anaemia experience severe forms COVID-19 leading to hospitalisation and death. Similarly, high burden of chronic obstructive pulmonary disease, high prevalence of tobacco consumption and low levels of expenditure on health and low levels of global health security score contribute to COVID-19 related deaths.ConclusionsDemographic, institutional, ecological, health system and politico-economic factors influenced the spectrum of COVID-19 infection, severity and death. We recommend multidisciplinary and integrated approaches to mitigate the identified factors and strengthen effective prevention strategies.

Background. Antimicrobial drug resistance is a global threat for treatment of infectious diseases and costs life and money and threatens health delivery system’s effectiveness. The resistance of E. coli to frequently utilized antimicrobial drugs is becoming a major challenge in Ethiopia. However, there is no inclusive countrywide study. Therefore, this study intended to assess the prevalence of E. coli resistance and antimicrobial-specific resistance pattern among E. coli clinical isolates in Ethiopia. Methods. Articles were retrieved from PubMed, Embase, and grey literature from 2007 to 2017. The main outcome measures were overall E. coli and drug-specific resistance patterns. A random-effects model was used to determine pooled prevalence with 95% confidence interval (CI), using DerSimonian and Laird method. In addition, subgroup analysis was conducted to improve the outcome. The study bias was assessed by Begg’s funnel plot. This study was registered in PROSPERO as follows: PROSPERO 2017: CRD42017070106. Results. Of 164 articles retrieved, 35 articles were included. A total of 19,235 study samples participated in the studies and 2,635 E. coli strains were isolated. Overall, E. coli antibacterial resistance was 45.38% (95% confidence interval (CI): 33.50 to 57.27). The resistance pattern ranges from 62.55% in Addis Ababa to 27.51% in Tigray region. The highest resistance of E. coli reported was to ampicillin (83.81%) and amoxicillin (75.79%), whereas only 13.55% of E. coli isolates showed resistance to nitrofurantoin. Conclusion. E. coli antimicrobial resistance remains high with disparities observed among regions. The bacterium was found to be highly resistant to aminopenicillins. The finding implies the need for effective prevention strategies for the E. coli drug resistance and calls for multifaceted approaches with full involvement of all stakeholders.