Population modifiable risk factors associated with under-5 acute respiratory tract infections and diarrhoea in 25 countries in sub-Saharan Africa (2014-2021): an analysis of data from demographic and health surveys.

Background: Identifying the critical modifiable risk factors for acute respiratory tract infections (ARIs) and diarrhoea is crucial to reduce the burden of disease and mortality among children under 5 years of age in sub-Saharan Africa (SSA) and ultimately achieving the Sustainable Development Goals (SDGs). We investigated the modifiable risk factors of ARI and diarrhoea among children under five using nationally representative surveys. Methods: We used the most recent demographic and health survey (DHS) data (2014-2021) from 25 SSA countries, encompassing a total of 253,167 children. Countries were selected based on the availability of recent datasets (e.g., DHS-VII or DHS-VIII) that represent the current socioeconomic situations. Generalised linear latent mixed models were used to compute odds ratios (ORs). Population attributable fractions (PAFs) were calculated using adjusted ORs and prevalence estimates for key modifiable risk factors among ARI and diarrhoeal cases. Findings: This study involved 253,167 children, with a mean age of 28.7 (±17.3) months, and 50.5% were male. The highest PAFs for ARI were attributed to unclean cooking fuel (PAF = 15.7%; 95% CI: 8.1, 23.1), poor maternal education (PAF = 13.4%; 95% CI: 8.7, 18.5), delayed initiation of breastfeeding (PAF = 12.4%; 95% CI: 9.0, 15.3), and poor toilets (PAF = 8.5%; 95% CI: 4.7, 11.9). These four modifiable risk factors contributed to 41.5% (95% CI: 27.2, 52.9) of ARI cases in SSA. The largest PAFs of diarrhoea were observed for unclean cooking fuel (PAF = 17.3%; 95% CI: 13.5, 22.3), delayed initiation of breastfeeding (PAF = 9.2%; 95% CI: 7.5, 10.5), household poverty (PAF = 7.0%; 95% CI: 5.0, 9.1) and poor maternal education (PAF = 5.6%; 95% CI: 2.9, 8.8). These four modifiable risk factors contributed to 34.0% (95% CI: 26.2, 42.3) of cases of diarrhoea in SSA. Interpretation: This cross-sectional study identified four modifiable risk factors for ARI and diarrhoea that should be a priority for policymakers in SSA. Enhancing home-based care and leveraging female community health workers is crucial for accelerating the reduction in under-5 mortality linked to ARI and diarrhoea in SSA. Funding: None.

Practical recommendations for planning and running live online education workshops for the rural health workforce.

AIM: This commentary presents practical and evidenced based guidelines for the development and delivery of real-time online training workshops aimed at rural health professionals. CONTEXT: Online learning is increasingly being used as an avenue for delivering education, particularly to rural and remote sites where barriers persist in upskilling health workers. Further, online learning has become essential during the coronavirus disease 2019 (COVID-19) pandemic. In response to the Australian 2020 COVID-19 social distancing requirements, our team rapidly transformed face-to-face educational workshops into an online format, to deliver over 20 workshops to more than 150 multidisciplinary staff across our large rural district. APPROACH: There are no published guidelines regarding the conversion of face-to-face education programs into an online format within health care. We conducted a review of the literature regarding the implementation of online education programs. Three broad categories of evidence were identified: participant qualities, content development and content deliverance. CONCLUSION: We present a set of practical and evidenced based recommendations, which will enhance live online workshops for a rural health workforce. These recommendations are derived both from published literature and our experience delivering our workshops. We argue that rural health professionals and organisations need relevant, up-to-date practical guidelines and more institutional support and training focused on creating and implementing live online educational programs in rural Australia.

Advantages and Pitfalls in Fluid Biomarkers for Diagnosis of Alzheimer's Disease.

Alzheimer's disease (AD) is a commonly occurring neurodegenerative disease in the advanced-age population, with a doubling of prevalence for each 5 years of age above 60 years. In the past two decades, there has been a sustained effort to find suitable biomarkers that may not only aide with the diagnosis of AD early in the disease process but also predict the onset of the disease in asymptomatic individuals. Current diagnostic evidence is supportive of some biomarker candidates isolated from cerebrospinal fluid (CSF), including amyloid beta peptide (Aß), total tau (t-tau), and phosphorylated tau (p-tau) as being involved in the pathophysiology of AD. However, there are a few biomarkers that have been shown to be helpful, such as proteomic, inflammatory, oral, ocular and olfactory in the early detection of AD, especially in the individuals with mild cognitive impairment (MCI). To date, biomarkers are collected through invasive techniques, especially CSF from lumbar puncture; however, non-invasive (radio imaging) methods are used in practice to diagnose AD. In order to reduce invasive testing on the patients, present literature has highlighted the potential importance of biomarkers in blood to assist with diagnosing AD.

Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer's Disease.

The risk of Alzheimer's disease (AD) increases with nonmodifiable conditions including age and lack of effective efficacious pharmacotherapy. During the past decades, the non-pharmacotherapy mode of treatment of dietary modification received extensive attention in AD research. In order to reduce the AD pathology and cognitive decline, various dietary patterns have been attempted including caloric restriction (CR), dietary approaches to stop hypertension (DASH), ketogenic diets (KD), Mediterranean diet (MedDi) and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet. Higher adherence to the MedDi diet was associated with decreases in cardiovascular and neurological disorders including AD and related cognitive decline. However, another emerging healthy dietary pattern MIND diet has also been associated with slower rates of cognitive decline and significant reduction of AD rate. Olive serves as one of the building block components of MedDi and MIND diets and the exerted potential health beneficial might be suggested due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). A few trials using medical food showed an optimal result in presymptomatic or early stages of AD. The review supports the notion that MedDi and MIND diets display potential for maintaining the cognitive function as nonpharmacological agents against AD pathology and proposed preventative mechanism through the presence of olive biophenols and presents the gaps along with the future directions.

Biophenols: Enzymes (ß-secretase, Cholinesterases, histone deacetylase and tyrosinase) inhibitors from olive (Olea europaea L.).

The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aß) producing enzyme (ß-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC50: 3.8 nM) followed by verbascoside (IC50: 6.3 nM) and olive fruit extract (IC50: 18 ng), respectively. Olive biophenol, quercetin exhibited strongest enzyme inhibitory activity against tyrosinase (IC50: 10.73 µM), BChE (IC50: 19.08 µM), AChE (IC50: 55.44 µM), and HDAC (IC50: 105.1 µM) enzymes. Furthermore, olive biophenol verbascoside (IC50: 188.6 µM), and hydroxytyrosol extreme extract (IC50: 66.22 µg) were showed the highest levels of inhibition against the HDAC enzyme. Neuroprotective capacity against levodopa-induced toxicity in neuroblastoma (SH-SY5Y) cells of olive biophenols were assessed, where rutin indicated the highest neuroprotection (74%), followed by caffeic acid (73%), and extract hydroxytyrosol extreme (97%), respectively. To the best of our knowledge, this is the first in vitro report on the enzymes inhibitory activity of olive biophenols. Taken together, our in vitro results data suggest that olive biophenols could be a promising natural inhibitor, which may reduce the enzyme-induced toxicity associated with the oxidative stress involved in the progression of AD. CHEMICAL COMPOUNDS USED IN THE STUDY: Acetylthiocholine iodide (PubChem CID: 74629); S-Butyrylthiocholine chloride (PubChem CID: 3015121); Caffeic acid (PubChem CID: 689043); Dimethyl sulfoxide (DMSO) (PubChem: 679); L-3,4-Dihydroxyphenylalanine (L-DOPA) (PubChem CID: 6047); 5,5'-Dithiobis (2-nitrobenzoic acid) (DTNB) (PubChem CID: 6254); Epigallocatechin gallate (EGCG) (PubChem CID: 65064); Ethylenediamine tetraacetic acid (EDTA) (PubChem CID: 6049); Galantamine hydrobromide (PubChem CID: 121587); l-Glutamine (PubChem CID: 5961); Hydroxytyrosol (PubChem CID: 82755); Kojic acid (PubChem CID: 3840); Luteolin (PubChem CID: 5280445); Oleuropein (PubChem CID: 5281544); Penicillin-streptomycin (PubChem CID: 131715954); Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Tris-HCl buffer (PubChem: 93573); Trypan blue (PubChem: 9562061).

Olive Biophenols Reduces Alzheimer's Pathology in SH-SY5Y Cells and APPswe Mice.

Alzheimer's disease (AD) is a major neurodegenerative disease, associated with the hallmark proteinacious constituent called amyloid beta (Aß) of senile plaques. Moreover, it is already established that metals (particularly copper, zinc and iron) have a key role in the pathogenesis of AD. In order to reduce the Aß plaque burden and overcome the side effects from the synthetic inhibitors, the current study was designed to focus on direct inhibition of with or without metal-induced Aß fibril formation and aggregation by using olive biophenols. Exposure of neuroblastoma (SH-SY5Y) cells with Aß42 resulted in decrease of cell viability and morphological changes might be due to severe increase in the reactive oxygen species (ROS). The pre-treated SH-SY5Y cells with olive biophenols were able to attenuate cell death caused by Aß42, copper- Aß42, and [laevodihydroxyphenylalanine (l-DOPA)] l-DOPA-Aß42-induced toxicity after 24 h of treatment. Oleuropein, verbascoside and rutin were the major anti-amyloidogenic compounds. Transgenic mice (APPswe/PS1dE9) received 50 mg/kg of oleuropein containing olive leaf extracts (OLE) or control diet from 7 to 23 weeks of age. Treatment mice (OLE) were showed significantly reduced amyloid plaque deposition (p < 0.001) in cortex and hippocampus as compared to control mice. Our findings provide a basis for considering natural and low cost biophenols from olive as a promising candidate drug against AD. Further studies warrant to validate and determine the anti-amyloid mechanism, bioavailability as well as permeability of olive biophenols against blood brain barrier in AD.

Olive (Olea europaea L.) Biophenols: A Nutriceutical against Oxidative Stress in SH-SY5Y Cells.

Plant biophenols have been shown to be effective in the modulation of Alzheimer's disease (AD) pathology resulting from free radical-induced oxidative stress and imbalance of the redox chemistry of transition metal ions (e.g., iron and copper). On the basis of earlier reported pharmacological activities, olive biophenols would also be expected to have anti-Alzheimer's activity. In the present study, the antioxidant activity of individual olive biophenols (viz. caffeic acid, hydroxytyrosol, oleuropein, verbascoside, quercetin, rutin and luteolin) were evaluated using superoxide radical scavenging activity (SOR), hydrogen peroxide (H2O2) scavenging activity, and ferric reducing ability of plasma (FRAP) assays. The identification and antioxidant activities in four commercial olive extracts-Olive leaf extractTM (OLE), Olive fruit extractTM (OFE), Hydroxytyrosol ExtremeTM (HTE), and Olivenol plusTM (OLP)-were evaluated using an on-line HPLC-ABTS•+ assay, and HPLC-DAD-MS analysis. Oleuropein and hydroxytyrosol were the predominant biophenols in all the extracts. Among the single compounds examined, quercetin (EC50: 93.97 µM) and verbascoside (EC50: 0.66 mM) were the most potent SOR and H2O2 scavengers respectively. However, OLE and HTE were the highest SOR (EC50: 1.89 µg/mL) and H2O2 (EC50: 115.8 µg/mL) scavengers among the biophenol extracts. The neuroprotection of the biophenols was evaluated against H2O2-induced oxidative stress and copper (Cu)-induced toxicity in neuroblastoma (SH-SY5Y) cells. The highest neuroprotection values (98% and 92%) against H2O2-induced and Cu-induced toxicities were shown by the commercial extract HTETM. These were followed by the individual biophenols, caffeic acid (77% and 64%) and verbascoside (71% and 72%). Our results suggest that olive biophenols potentially serve as agents for the prevention of neurodegenerative diseases such as AD, and other neurodegenerative ailments that are caused by oxidative stress.

Biophenols pharmacology against the amyloidogenic activity in Alzheimer's disease.

Alzheimer's disease characterized by misfolding, aggregation, and accumulation of amyloid fibrils in an insoluble form in the brain, is often known as amyloidosis. The process of aggregation follows a mechanism of seeded polymerization. For decades, a great number of failures in Alzheimer's disease (AD) drug development, with both small molecules and immunotherapies failing to establish a drug/placebo difference or having an unacceptable toxicity have led to the therapeutic research interest towards a group of anti-amyloidogenic compounds originated from plants called biophenols. A number of in vitro and in vivo studies have demonstrated that the plant biophenols bind with amyloid beta (Aß) toxic oligomers and reducing the fibril formation and toxicity. The exact mechanism of biophenols action against Aß toxicity is unknown, while studies have suggested the amyloid-binding affinity of biophenols affecting Aß on various levels, e.g. by direct inhibiting fibril formation or steering oligomer formation into unstructured, inhibiting Aß aggregation, and promoting nontoxic pathways. Furthermore, biophenols involved in the inhibition of Aß progression (e.g., oxidative stress and neuroinflammation) and effecting the amyloid precursor protein processing through the direct or indirect inhibition of ß-secretase (BACE-1), γ-secretase and/or activation of α-secretase. This critical review account for the biophenols as magic bullet targeting against Aß, and simulation the results on how biophenols interact with the Aß monomers and oligomers, highly desirable knowledge for predicting new efficient nutraceutical drugs.

Oleuropein in olive and its pharmacological effects.

Olive from Olea europaea is native to the Mediterranean region and, both the oil and the fruit are some of the main components of the Mediterranean diet. The main active constituents of olive oil include oleic acid, phenolic constituents, and squalene. The main phenolic compounds, hydroxytyrosol and oleuropein, give extra-virgin olive oil its bitter, pungent taste. The present review focuses on recent works that have analyzed the relationship between the major phenolic compound oleuropein and its pharmacological activities including antioxidant, anti-inflammatory, anti-atherogenic, anti-cancer activities, antimicrobial activity, antiviral activity, hypolipidemic and hypoglycemic effect.

Cardioprotective and neuroprotective roles of oleuropein in olive.

Traditional diets of people living in the Mediterranean basin are, among other components, very rich in extra-virgin olive oil, the most typical source of visible fat. Olive is a priceless source of monounsaturated and di-unsaturated fatty acids, polyphenolic antioxidants and vitamins. Oleuropein is the main glycoside in olives and is responsible for the bitter taste of immature and unprocessed olives. Chemically, oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol, which possesses beneficial effects on human health, such as antioxidant, antiatherogenic, anti-cancer, anti-inflammatory and antimicrobial properties. The phenolic fraction extracted from the leaves of the olive tree, which contains significant amounts of oleuropein, prevents lipoprotein oxidation. In addition, oleuropein has shown cardioprotective effect against acute adriamycin cardiotoxicity and an anti-ischemic and hypolipidemic activities. Recently, oleuropein has shown neuroprotection by forming a non-covalent complex with the Aß peptide, which is a key hallmark of several degenerative diseases like Alzheimer and Parkinson. Thus, a large mass of research has been accumulating in the area of olive oil, in the attempt to provide evidence for the health benefits of olive oil consumption and to scientifically support the widespread adoption of traditional Mediterranean diet as a model of healthy eating. These results provide a molecular basis for some of the benefits potentially coming from oleuropein consumption and pave the way to further studies on the possible pharmacological use of oleuropein to prevent or to slow down the cardiovascular and neurodegenerative diseases.