COVID-19: breaking down a global health crisis.

Coronavirus disease 2019 (COVID-19) is the second pandemic of the twenty-first century, with over one-hundred million infections and over two million deaths to date. It is a novel strain from the Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); the 7th known member of the coronavirus family to cause disease in humans, notably following the Middle East Respiratory syndrome (MERS), and Severe Acute Respiratory Distress Syndrome (SARS). The most characteristic feature of this single-stranded RNA molecule includes the spike glycoprotein on its surface. Most patients with COVID-19, of which the elderly and immunocompromised are most at risk, complain of flu-like symptoms, including dry cough and headache. The most common complications include pneumonia, acute respiratory distress syndrome, septic shock, and cardiovascular manifestations. Transmission of SARS-CoV-2 is mainly via respiratory droplets, either directly from the air when an infected patient coughs or sneezes, or in the form of fomites on surfaces. Maintaining hand-hygiene, social distancing, and personal protective equipment (i.e., masks) remain the most effective precautions. Patient management includes supportive care and anticoagulative measures, with a focus on maintaining respiratory function. Therapy with dexamethasone, remdesivir, and tocilizumab appear to be most promising to date, with hydroxychloroquine, lopinavir, ritonavir, and interferons falling out of favour. Additionally, accelerated vaccination efforts have taken place internationally, with several promising vaccinations being mass deployed. In response to the COVID-19 pandemic, countries and stakeholders have taken varying precautions to combat and contain the spread of the virus and dampen its collateral economic damage. This review paper aims to synthesize the impact of the virus on a global, micro to macro scale.

Entamoeba histolytica and amoebic liver abscess in northern Sri Lanka: a public health problem.

Entamoeba histolytica (E. histolytica) is a facultative protozoan parasite implicated in amoebic liver abscesses (ALA), the most common extraintestinal manifestation of this infection. E. histolytica is endemic to sub-tropical and tropical countries and has been a major public health concern in northern Sri Lanka (SLK) for the last three decades. This has been attributed to a multitude of factors such as poor sanitation, hygiene, male sex, middle age, overcrowding, unsanitary practices in the production of indigenous alcoholic beverages, and alcohol consumption. Additionally, while rates of E. histolytica have declined substantially throughout the rest of the island, largely due to better infrastructure, it remains pervasive in the northern peninsula, which is generally less developed. Infection arises primarily from fecal-oral transmission through the consumption of contaminated drinking water containing cysts. Upon ingestion, cysts multiply into trophozoites and colonize the host colonic mucosa using lectin and cysteine proteases as virulence factors, leading to host invasion. Symptoms occur along a spectrum, from asymptomatology, to pyrexia, abdominal cramping, and amoebic dysentery. Colonization of the colon results in the formation of distinct flask-shaped ulcers along the epithelium, and eventual penetration of the lamina propria via the production of matrix metalloproteinases. ALA then develops through trophozoite migration via the mesenteric hepatic portal circulation, where microabscesses coalesce to form a single, large right-lobe abscess, commonly on the posterior aspect. The progression of infection to invasive disease is contingent on the unique interplay between host and pathogen factors, such as the strength of host-immunity to overcome infection and inherent pathogenicity of the Entamoeba species. As a preventable illness, E. histolytica complications such as ALA impose a significant burden on the healthcare system. This mini-review highlights epidemiological trends, risk factors, diagnostic modalities, treatment approaches, and opportunities for prevention of E. histolytica-induced ALA, to help address this endemic problem on the island of SLK.

TNF-α Induces a Pro-Inflammatory Phenotypic Shift in Monocytes through ACSL1: Relevance to Metabolic Inflammation.

BACKGROUND/AIMS: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes. METHODS: Monocytes (Human monocytic THP-1 cells) were stimulated with TNF-α. Inflammatory phenotypic markers (CD16, CD11b, CD11c and HLA-DR) expression was determined with real time RTPCR and flow cytometry. IL-1ß and MCP-1 were determined by ELISA. Signaling pathways were identified by using ACSL1 inhibitor, ACSL1 siRNA and NF-κB reporter monocytic cells. Phosphorylation of NF-κB was analyzed by western blotting and flow cytometry. RESULTS: Our data show that TNF-α induced significant increase in the expression of CD16, CD11b, CD11c and HLA-DR. Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers. Using ACSL-1 siRNA, we further demonstrate that TNF-α-induced inflammatory markers expression in monocytic cells requires ACSL1. In addition, IL-1b and MCP-1 production by TNF-α activated monocytic cells was significantly blocked by the inhibition of ACSL-1 activity. Interestingly, elevated NF-κB activity resulting from TNF-α stimulation was attenuated in ACSL1 deficient cells. CONCLUSION: Our findings provide an evidence that TNF-α-associated inflammatory polarization in monocytes is an ACSL1 dependent process, which indicates its central role in TNF-α-driven metabolic inflammation.