Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis,transmission and therapeutic evaluation

There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections. The coronavirus family, which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2, crossed the species barrier and infected humans, causing a global outbreak in the 21^st century. Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials, animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines. The ideal animal models should reflect the viral replication, clinical signs, and pathological responses observed in humans. Different animal species should be tested to establish an appropriate animal model to study the disease pathology, transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019. In this context, the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.     

Prevalence and Associated Features of Gastroesophageal Reflux Symptoms in a Caucasian-Predominant Adolescent School Population

OBJECTIVE: To determine the prevalence of esophageal symptoms and associated symptoms of gastroesophageal reflux symptoms in 14-18 year-old high school students and the percentage of symptomatic adolescents who saw a physician or received medications. DESIGN AND SETTING: A cross-sectional questionnaire administered to students at two high schools. PARTICIPANTS: 1,286 completed questionnaires were analyzed. The study sample consisted of 57% Caucasians and 57% males, with a mean age of 15.7 (+/-1.3) years. INTERVENTION: No intervention was used. Participants completed questionnaires only. RESULTS: 714 students (56%) reported at least one esophageal or respiratory symptom. Esophageal symptoms reported were: heartburn (22%), regurgitation (21%), and dysphagia (15%). Respiratory symptoms reported were: shortness of breath (24%), wheezing (20%), and cough (18%). Students with at least one esophageal symptom were more likely to experience at least one respiratory symptom than were students with no esophageal symptoms (52% vs. 25%; p < 0.001). Cigarette, alcohol, and non-steroidal anti-inflammatory drug use were risk factors for both respiratory and esophageal symptoms. Of those experiencing one or more of these symptoms, 4% reported that the symptoms affected their daily activities, 23% visited a physician, and 25% took medication in the past year. CONCLUSIONS: Esophageal symptoms of gastroesophageal reflux are frequent in adolescents. Fewer than 25% of students with gastroesophageal reflux symptoms consulted a physician and/or took medications.     

The pathophysiological and immunological background of the monkeypox virus infection: An update

In addition to the COVID-19 waves, the globe is facing global monkeypox (MPX) outbreak. MPX is an uncommon zoonotic infection characterized by symptoms similar to smallpox. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus that belongs to the genus Orthopoxvirus (OPXV). MPXV, which causes human disease, has been confined to Africa for many years, with only a few isolated cases in other areas. Outside of Africa, the continuing MPXV outbreak in multiple countries in 2022 is the greatest in recorded history. The current outbreak, with over 10 000 confirmed cases in over 50 countries between May and July 2022, demonstrates that MPXV may travel rapidly among humans and pose a danger to human health worldwide. The rapid spread of such outbreaks in recent times has elevated MPX to the status of a rising zoonotic disease with significant epidemic potential. While the MPXV is not as deadly or contagious as the variola virus that causes smallpox, it poses a threat because it could evolve into a more potent human pathogen. This review assesses the potential threat to the human population and provides a brief overview of what is currently known about this reemerging virus. By analyzing the biological effects of MPXV on human health, its shifting epidemiological footprint, and currently available therapeutic options, this review has presented the most recent insights into the biology of the virus. This study also clarifies the key potential causes that could be to blame for the present MPX outbreak and draw attention to major research questions and promising new avenues for combating the current MPX epidemic.     

Methylene blue for diagnosis of displaced atrial lines

Methylene blue (aniline violet, tetra-methylthionine chloride) has several important uses in clinical medicine, including diagnosis of displaced central lines. After cardiac surgery, three infants with suspected displacement of direct atrial lines were given methylene blue. After injection of the dye into the atrial lines, bluish discolouration was identified in their chest drainage. Use of methylene blue in small amounts appears to be a safe and effective way of diagnosing extravasation of fluid from displaced central lines.     

Medullomyoblastoma: A case report.

Medullomyoblastoma is a rare tumour seen in childhood. We report a medullomyoblastoma occurring in the cerebellar vermis of a 4 year old boy. The light microscopic features, immunohistochemistry and histogenesis are described.     

Early experience with Levosimendan in children with ventricular dysfunction.

OBJECTIVE: To describe our preliminary experience with Levosimendan, a new calcium-sensitizing agent in critically unwell infants and children with severe heart failure. DESIGN: Retrospective cohort analysis. SETTING: Pediatric intensive care unit. PATIENTS: Fifteen children aged 7 days to 18 yrs (median age 38 months) with severe myocardial dysfunction secondary to end-stage heart failure, or acute heart failure, who were inotrope-dependent (requiring at least one catecholamine). INTERVENTIONS: A single dose (bolus and intravenous infusion over 24-48 hrs) of Levosimendan was given under continuous hemodynamic monitoring in our intensive care unit. Eleven children received a single dose, three children received two doses, and one child received four doses. Echocardiographic assessments of ventricular function were made before and 3-5 days after Levosimendan infusion. MEASUREMENTS AND MAIN RESULTS: Heart rate, systolic pressure, diastolic pressure, mean blood pressure, and central venous pressure were unchanged during and after Levosimendan. Levosimendan allowed for discontinuation of catecholamines in ten patients and a dose reduction in three. The dose of dobutamine was reduced from 6.4 microg/kg/min pre-Levosimendan to 1.8 microg/kg/min on day 5 (p < .01). Ejection fraction for the group as a whole improved from 29.8% to 40.5% (p = .015); this did not increase significantly in patients with end-stage heart failure but increased by 63% in the children with acute heart failure. CONCLUSIONS: Levosimendan can be safely administered to infants and children with severe heart failure. Levosimendan allowed for substantial reduction in catecholamine infusions in children with end-stage or acute heart failure and also produced an objective improvement in myocardial performance in children with acute heart failure.     

Protective effect of the ethanolic and methanolic leaf extracts of Madhuca longifolia against diclofenac-induced toxicity in female Wistar albino rats

BackgroundDiclofenac is commonly prescribed Non-Steroidal Anti-Inflammatory Drug (NSAIDs) as it has anti-inflammatory, analgesic and anti-pyretic properties. Long term usage and over-dosage of diclofenac is associated with adverse effects like drug-induced liver injury, gastrointestinal and renal toxicity. The therapeutic uses of medicinal plants have gained a prominent role in recent years. Madhuca longifolia is a tree found throughout India, which is known to have several pharmacological activities. The aim of our study is to investigate the potential effect of the ethanolic and methanolic leaf extracts of M. longifolia against diclofenac-induced toxicity.MethodsThe rats used for the experiment were divided into seven groups. Group-1 was the normal control. Group-2 was administered with diclofenac (50 mg/kg b.w./day/ip) on the 4^th and the 5^th day. Group-3 was treated with diclofenac and ELEML (500 mg/kg b.w./day/po) on all 5 days. Group-4 was treated with diclofenac and MLEML (500 mg/kg b.w./day/po) on all 5 days. Standard drug silymarin (25 mg/kg b.w./day/po) was given to the rats of group-5 along with diclofenac. Group-6 and group–7 were treated with ethanolic leaf extract and methanolic leaf extract of M. longifolia respectively. After the study period, the rats were evaluated for parameters like liver and renal markers, antioxidants and histopathological changes.ResultsThis study has proved the beneficial effect of ethanolic and methanolic leaf extract of M. longifolia against diclofenac-induced toxicity wherein ethanolic leaf extract showed a better result than methanolic leaf extract.ConclusionOur study has concluded the beneficial effect of ethanolic and methonolic leaf extract of Madhuca longifolia against DFC-induced toxicity. This study proves that it has potential effect on hepato, renal and gastro toxicity in female Wistar albino rats. It can further be studied to understand its mechanism in treating toxicity.