2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

https://hull-repository.worktribe.com/preview/1797952/1-s2.0-S0140673618322797-main.pdf

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

https://openresearch-repository.anu.edu.au/bitstream/1885/164632/2/01_Bin%2bSayeed_Global%252C_regional%252C_and_national_2018.pdf

Global, regional, and national incidence, prevalence, andyears lived with disability for 354 diseases and injuries for195 countries and territories, 1990–2017: a systematicanalysis for the Global Burden of Disease Study 2017

https://research-information.bris.ac.uk/ws/files/259213304/PIIS0140673620309259.pdf

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Estimates of the worldwide incidence and mortality from 36 cancers and for all cancers combined for the year 2018 are now available in the GLOBOCAN 2018 database, compiled and disseminated by the International Agency for Research on Cancer (IARC). This paper reviews the sources and methods used in compiling the cancer statistics in 185 countries. The validity of the national estimates depends upon the representativeness of the source information, and to take into account possible sources of bias, uncertainty intervals are now provided for the estimated sex- and site-specific all-ages number of new cancer cases and cancer deaths. We briefly describe the key results globally and by world region. There were an estimated 18.1 million (95% UI: 17.5-18.7 million) new cases of cancer (17 million excluding non-melanoma skin cancer) and 9.6 million (95% UI: 9.3-9.8 million) deaths from cancer (9.5 million excluding non-melanoma skin cancer) worldwide in 2018.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.31937

Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods

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.

/pdf/targeting-renin-angiotensin-system-against-alzheimer-s-1lua89ru8k.pdf

Targeting Renin-Angiotensin System Against Alzheimer's Disease

Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors. Among these, NSs (especially allopregnanolone) have high potency and extensive GABA-A receptors and hence demonstrate anticonvulsant, anesthetic, central cytoprotectant, and baroreflex inhibitory effects. NSs are also involved in mood and learning via serotonin and anti-nociceptive activity via T-type voltage-gated Ca2+ channels. Moreover, they are modulators of mitochondrial function, synaptic plasticity, or regulators of apoptosis, which have a role in neuroprotective via voltage-dependent anion channels receptors. For proper functioning, NASs need to be in their normal level, whereas excess and deficiency may lead to abnormalities. When they are below the normal, NSs could have a part in development of depression, neuro-inflammation, multiple sclerosis, experimental autoimmune encephalitis, epilepsy, and schizophrenia. On the other hand, stress and attention deficit disorder could occur during excessive level. Overall, NASs are very important molecules with major neuropsychiatric activity.

/pdf/neuroactive-steroids-receptor-interactions-and-responses-4qd65jdfa3.pdf

Neuroactive Steroids: Receptor Interactions and Responses

To date, there is no cure or disease-modifying agents available for most well-known neurological disorders. Current therapy is typically focused on relieving symptoms and supportive care in improving the quality of life of affected patients. Furthermore, the traditional de novo drug discovery technique is more challenging, particularly for neurological disorders. Therefore, the repurposing of existing drugs for these conditions is believed to be an efficient and dynamic approach that can substantially reduce the investments spent on drug development. Currently, there is emerging evidence that suggests the potential effect of a beta-lactam antibiotic, ceftriaxone (CEF), to alleviate the symptoms of different experimentally-induced neurological disorders: Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, epileptic-seizure, brain ischemia, traumatic brain injuries, and neuropathic pain. CEF also affects the markers of oxidative status and neuroinflammation, glutamatergic systems as well as various aggregated toxic proteins involved in the pathogenesis of different neurological disorders. Moreover, it was found that CEF administration to drug dependent animal models improved the withdrawal symptoms upon drug discontinuation. Thus, this review aimed to describe the effects of CEF against multiple models of neurological illnesses, drug dependency, and withdrawal. It also emphasizes the possible mechanisms of neuroprotective actions of CEF with respective neurological maladies.

/pdf/repurposing-of-the-b-lactam-antibiotic-ceftriaxone-for-12augnpum9.pdf

Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review.

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.

/pdf/drug-resistance-patterns-of-escherichia-coli-in-ethiopia-a-3cs9j6u4oj.pdf

Drug Resistance Patterns of Escherichia coli in Ethiopia: A Meta-Analysis.

Background. Aloe megalacantha Baker (Xanthorrhoeaceae) is one of the Aloe species widely distributed in Ethiopia. The leaf latex of the plant is used for treatment of wounds, inflammation, and other multiple ailments in Ethiopian traditional medicine. Purpose. The aim of this study was to evaluate in vivo wound healing and anti-inflammatory activities of the leaf latex of Aloe megalacantha in mice. Methods. The wound healing activity of the leaf latex of the plant was studied topically by incorporating the latex in simple ointment base in a concentration of 5% (w/w) and 10% (w/w) using excision and incision models. In these models, wound contraction, period of epithelialization, and breaking strength of the wounded skin were determined. Carrageenan induced inflammation of paw model was also used to assess the anti-inflammatory activity of the leaf latex at doses of 200 mg/kg, 400mg/kg, and 600 mg/kg. The level of inflammation suppressions were measured at 1, 2, 3, and 4 hrs after carrageenan injection, and then the percentages of inflammation inhibition were computed as compared with the negative control. Result. In both wound models, mice treated with 5% (w/w) and 10% (w/w) latex ointment showed a significant (p<0.05) increment in the rate of wound contraction, reduction in epithelialization time, and higher skin breaking strength. Besides, the latex also exhibited a dose-dependent significant (p<0.05) reductions of inflammation as compared to negative control groups. Conclusion. The overall results of this study demonstrate that the leaf latex of A. megalacantha possesses wound healing and anti-inflammatory activities which can scientifically substantiate the traditional use of the plant as a wound healing agent.

/pdf/in-vivo-wound-healing-and-anti-inflammatory-activities-of-2tdbtgfvu8.pdf

Kald Beshir Tuem

Papers

Targeting Renin-Angiotensin System Against Alzheimer's Disease

Neuroactive Steroids: Receptor Interactions and Responses

Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review.

Drug Resistance Patterns of Escherichia coli in Ethiopia: A Meta-Analysis.

In Vivo Wound Healing and Anti-Inflammatory Activities of Leaf Latex of Aloe megalacantha Baker (Xanthorrhoeaceae)