Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The evolution of H5N1 has attracted significant interest 1-4 due to linkages with avian 5,6 and human infections 7,8. The basic tenets of influenza genetics 9 attribute genetic drift to replication errors caused by a polymerase complex that lacks a proof reading function. However, recent analysis 10 of swine influenza genes identifies regions copied with absolute fidelity for more than 25 years. In addition, polymorphism tracing of clade 2.2 H5N1 single nucleotide polymorphisms identify concurrent acquisition 11 of the same polymorphism onto multiple genetic backgrounds in widely dispersed geographical locations. Here we show the aggregation of regional clade 2.2 polymorphisms from Germany, Egypt, and sub-Sahara Africa onto a human Nigerian H5N1 hemagglutinin (HA), implicating recombination in the dispersal and aggregation of single nucleotide polymorphisms from closely related genomes

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences

HEALING POTENCY OF HAEMATOCOCCUS PLUVIALIS EXTRACT FOR TREATING TYPE 2 DIABETES IN RATS

Objective: The present study aims to evaluate the antidiabetic effect of ethanolic extract of Haematococcus pluvialis (H. pluvialis) in streptozotocin (STZ)-induced diabetic rats.Methods: The antidiabetic activity of H. pluvialis was investigated by the determination of glucose and insulin levels, aspartate (AST), alanine transaminases (ALT), lipid profile including total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density-lipoprotein-cholesterol (HDL-C). Histopathological examination of pancreas and liver were also carried out.Results: The results revealed that the levels of glucose, TC, TG, LDL-C as well as AST and ALT enzyme activities were increased significantly in diabetic rats. While, insulin and HDL-C levels decreased significantly in STZ-induced diabetic rats. The remediation of diabetic rats with H. pluvialis attenuated the elevated levels of glucose, TC, TG, LDL-C as well as AST and ALT activities in diabetic rats. Besides, it improved insulin, HDL-C levels, pancreas and hepatic architectures.Conclusion: H. pluvialis extract has a promising antidiabetic potency through attenuation of several metabolic disorders associated diabetes

MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS IN RAW CAPRINE MILK

ABSTRACT One hundred and fifty individual caprine milk samples were analyzed for Mycobacterium avium subsp. paratuberculosis (MAP). Out of 150 samples tested for MAP, 53 (35.33%) samples could be detected by Enzyme-Linked Immunosobent Assay (ELISA) technique. However, one (0.67%) sample was found positive in Polymerase Chain Reaction (PCR) method and failed to be isolated from all the examined samples

The effects of creamy and skimmed dairy products (milk, yoghurt and cheese) on lipid profile of healthy rats

Milk and dairy products contain saturated fatty acids that have different effects on human health status and are risk factors for many diseases including cardiovascular disease and diabetes mellitus. The present study aimed to evaluate the impact of creamy and skimmed milk administration and certain dairy products (yoghurt and cheese) on healthy rats. A total of forty-nine healthy male Sprague Dawley rats were divided to seven groups. The treatment diet includes creamy and skimmed milk, creamy and skimmed yoghurt, creamy and skimmed cheese. After 60 days of consumption, body weight (BW) and lipids profile were measured. The final BW was higher in rats fed with creamy milk (256.40±23.81), and rats fed with creamy yoghurt (262.71±25.41) and creamy cheese (266.57±22.71). A significant elevation in the liver (aspartate aminotransferase and serum alanine) and kidney functions (urea, creatinine, and uric acid) have been observed in rats fed with fresh creamy whole milk and skimmed milk groups. The measured lipid profile has increased, especially rats fed with creamy milk, creamy, and skimmed cheese. In which, the total cholesterol has reached 159.70, 170.11 and 160.11. Meanwhile, the triglycerides increased to 125.51, 117.35 and 110.41. The low-density lipoprotein and the very low-density lipoprotein have also elevated with their atherogenic indexes at 5.2±0.55, 5.74±0.68 and 5.31±0.44 respectively. On the other hand, notable decreases were seen in the high-density lipoprotein cholesterol and liver glycogen compared to rats fed with control diet. In conclusion, both skimmed and creamy yoghurt indicated healthy nutritional properties, especially with lipid and atherogenic indexes by means of healthy liver and renal functions. Thus, yoghurt (creamy or skimmed) improved the healthy rats' lipid profile while creamy milk additions increased the BW. However, cheese (creamy or skimmed) is suggested to be avoided due to hyperlipidemic conditions in rats

Chaos in Cancer Tumor Growth Model with Commensurate and Incommensurate Fractional-Order Derivatives

Analyzing the dynamics of tumor-immune systems can play an important role in the fight against cancer, since it can foster the development of more effective medical treatments. This paper was aimed at making a contribution to the study of tumor-immune dynamics by presenting a new model of cancer growth based on fractional-order differential equations. By investigating the system dynamics, the manuscript highlights the chaotic behaviors of the proposed cancer model for both the commensurate and the incommensurate cases. Bifurcation diagrams, the Lyapunov exponents, and phase plots confirm the effectiveness of the conceived approach. Finally, some considerations regarding the biological meaning of the obtained results are reported through the manuscript

Synthesis and in silico investigation of organoselenium-clubbed Schiff bases as potential mpro inhibitors for the SARS-CoV-2 replication

Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6–311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from −8.19 to −7.33 Kcal/mol for 4c and 4a to −6.10 to −6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good Mpro inhibitors. Moreover, the drug-likeness studies, including Lipinski’s rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic

Synthesis of new organoselenium-based succinanilic and maleanilic derivatives and in silico studies as possible SARS-CoV-2 main protease inhibitors

Herein we report the synthesis of organic selenide-based maleanilic and succinanilic acids in good yields (up to 95%). Their structural identities were elucidated by spectroscopic techniques (e.g., IR, 1H- & 13C-NMR, and MS). The ADMET analysis, molecule electrostatic potential map, DFT, and frontier molecular orbital were used to study the organoselenium compounds’ pharmacokinetics, drug-likeness characteristics, geometries, and chemical and electronic properties. Moreover, a molecular docking tool was employed to investigate the organic selenides’ ability to inhibit the SARS-CoV-2 Mpro target (PDB: 7BFB). Within this context, organic selenides exhibited promising binding affinities to the SARS-CoV-2 Mpro receptor in the following order (12 > 11 > 10 > 9 > 7 > 8). Furthermore, molecular dynamics simulations were also carried out for 200 ns to evaluate the exact behavior of the most active compound (12) within the Mpro binding pocket of SARS-CoV-2 compared with its co-crystallized inhibitor (Co)

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112