ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF JUSTICIA SPICIGERA ETHYL ACETATE FRACTION AND CHARACTERIZATION OF ITS ANTHOCYANIN CONTENT

Objective: The antioxidant and hepatoprotective activities of ethyl acetate (EA) fraction of the dried aerial part of Justicia spicigera were evaluated and the characterization of its anthocyanin content was done. Methods: Hepatic fibrosis was induced by carbon tetrachloride (CCl4) in rats. The ethyl acetate fraction was obtained by successive liquid/liquid fractionation of the crude cold ethanolic extract and the pigments were characterized by HPLC technique. The in vitro studies were carried out through evaluation of the EA fraction on the attenuation of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals. The in vivo biological evaluation was done in CCl4 injured rats through determination of liver function indices, oxidative stress markers and the histopathological picture of the treated liver.Results: The phenolic content in the EA fraction was 42.94 mg/g. Twelve anthocyanins were identified, the major of which are peonidin 3, 5-diglucoside (64.30%), malvidin 3, 5-diglucoside (10.59%) and petunidin 3,5-diglucoside (4.71%). Treatment of CCl4 intoxicated rats with EA fraction recorded improvement in the liver function indices and oxidative stress markers. The histopathological observations confirmed our results.Conclusion: The ethyl acetate fraction of the dried aerial part of Justicia spicigera recorded antioxidant and hepato protective activities.Â

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Biotechnological Production of Volatile and Non-Volatile Antioxidant Compounds From Fermented Soy Bean Meal with Trichoderma sp

ABSTRACT Three strains of Trichoderma sp. were screened for β-glucosidase activity and their potential for the breakdown of isoflavone glucosides to the biologically active aglycones in defatted soy bean meal. The main flavonoid products of fermentation process were evaluated by qualitative and quantitative HPLC analysis. Also, the production of volatile compounds in both the crude soy meal (CSM) and defatted soy meal (DSM) cultured by Trichoderma harzianam F.555 were determined by GC-MS. Isoflavones in defatted soy meal fermented by Trichoderma viride, F-516 or T. harzianam F-555 or T. reesei F-417 at 37 °C for 48 h were determined. Daidzein and genistein aglycones concentrations were significantly increased after fermentation to 162% and 362.4 % for T. reesei; 151.3% and 944 % for T. harzianam and up to 80.6% and 711 % for T. viride, respectively. Results showed that fermented defatted soy meal by T. harzianam F-555 T. viride F-516 and T. reesei F-417 increased levels of bioactive genistein (10.44, 8.11 and 4.62 folds, respectively). Moreover, defatted soy meals were fermented separately by T. reesew, T. harzianam F-555 and T. viride F-516 showed highly significant increase of daidzein (2.64, 2.51 and 1.82 folds, respectively) in comparison to unfermented defatted soy meal (DSM). The levels of aglycones increased, while the corresponding levels of glucosides decreased. Furthermore, in fermented defatted soy meal (FDSM) with T. harzianam, compounds such as Butylated Hydroxytoluene (38.19 %), 1,4-Di-anhydro-mannitol (14.25 %) and 2-Dimethyl (isopropyl) silyloxy methyl tetra -hydrofurane (9.62 %) were present at high concentrations as dominant volatiles. While, the major volatile compounds in fermented crude soy meal (FCSM) were 9,12-Octadecadienoicacid (Z,Z), methyl ester (28.08 %), 2,2-Bis[4-(4,6-dichloro-1,3,5-triazin-2-yl)oxy]phenyl]1,1,1,3,3,3hexafluoropropane (10.61 %), Oleic Acid (10.61 %), and 9-Octadecenoic acid-3-[(1-oxohexadecyl)oxy]-2-[(1-oxooctadecyl)-oxy] propyl ester (9.08 %). Total phenolic content and in vitro antioxidant activity of ethanolic extract of (FDSM) with T. harzianam were higher than that in (CSM), (FCSM) and (DSM). Moreover, the major volatile antioxidant-active compound was butylated hydroxytoluene. The current findings indicate that fermentation process carried out in (DSM) inoculated with different microorganisms produced significant changes in flavonoids and volatile contents. Therefore, both volatile and non volatile products of (FDSM) are considered as prospective bioactive and functional by-products of soybean oil production. These data suggest that microbial fermentation of (DSM) might be valuable sources of antioxidant that can be applied in food and pharmaceutical industry

Spectroscopic, crystal structural, theoretical and biological studies of phenylacetohydrazide Schiff base derivatives and their copper complexes

Two phenylacetohydrazide Schiff base derivatives: N’-(1-(2-hydroxyphenyl)ethylidene)-2-phenylacetohydrazide, HL1, and N’-((1-hydroxynaphthalen-2-yl)methylene)-2-phenylacetohydrazide, HL2, were synthesized. HL1 dimerizes in presence of HCl, probably via radical mechanism to give (2,2’-((1E)-hydrazine-1,2-diylidenebis(ethan-1-yl-1-ylidene))diphenol (DIM). Thermal reactions of Cu(II) ions with the two Schiff base ligands resulted in formation of the binuclear complexes [(CuL1)2] and [(CuL2)2]. The stoichiometry and structures of the reported compounds were investigated by several spectroscopic and analytical techniques. The structure of the HL1 ligand and its complex [(CuL1)2] as well as the DIM derivative were analyzed by single crystal X-ray analysis. The X-ray analysis revealed the binuclear coordination of the copper complex with the formation of five- and six-membered rings with every ligand. The molecular geometries of the ligands and their copper complexes were investigated using the DFT‐B3LYP/GENECP level of theory. The optimized structures of the studied complexes are consistent with the finding of the X-ray analysis. The quantum, non-quantum global reactivity descriptors and the non-linear optical properties were calculated. Biological studies including, antimicrobial and antioxidant activities of the complexes along with fluorescence quenching studies and viscosity measurements are carried out. The molecular docking of the two ligands and [(CuL2)2] complex is also reported. The different biological studies as well as molecular docking are correlated to each other and supported the fact that the complexes can bind to DNA via intercalative mode and showed a various DNA binding potency.peerReviewe

Vitamin D as a Key Player in Modulating Rheumatoid Arthritis-derived Immune Response

Rheumatoid arthritis (RA) is a systemic inflammatory disease with chronic nature of joints related to autoimmunity. Vitamin D was found to modulate cell growth, function of immune cells and anti-inflammatory action. The aims of that study were to investigate serum level of vitamin D and some cytokines and to identify the correlation between vitamin D and these cytokines in RA. Totally 40 RA patients without vitamin D supplement were involved in this study. Serum level of vitamin D, interleukin-6 (IL-6), IL-10, IL-35, C-reactive protein (CRP) and tumor necrosis factor α (TNF-α), all of them were measure in all patients by enzyme-linked immunosorbent assay (ELISA). Patients were classified according to Vitamin D levels into two groups; RA patients with Vit. D deficiency (n=25) and RA patients with Vit. D sufficiency (n=15). IL-6 was lower significantly (P = 0.03) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. IL-10 and IL-35 were higher significantly (P = 0.0234, P = 0.0356 respectively) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. Vit. D was significantly positively correlated with both IL-10 (r = 0.4516, P = 0.0034) and IL-35 (r = 0.3424, P = 0.0329) and negatively correlated with IL-6 (r = -0.3188, P = 0.0479). Sufficient serum level of Vit. D is correlated with higher level of anti-inflammatory cytokines (IL-10 and IL-35) and lower level of IL-6. This support the immunomodulatory effect of Vit. D in RA

Dismantling Parkinson’s disease with herbs: MAOB inhibitory activity and quantification of chemical constituents using HPLC-MS/MS of Egyptian local market plants

Withania somnifera, Angelica sinensis, Glycyrrhiza glabra, and Simmondsia chinensis were acquired from the Egyptian market, profiled for their chemical constituents, screened for the in-vitro MAO-B inhibitory activity and evaluated for the total phenolic content. Thirty compounds were characterized in the selected herbs using HPLC-MS/MS. In-vitro MAO-B inhibitory activity and total phenolic content of the acquired herbs were compared with those of a prepared herbal formula consisting of a mixture of equal amounts of the four mentioned herbs. The most potent MAO-B inhibitory activity was exerted by the methanol extract of the prepared formula (IC50 of 712.19 ± 13.90 ng/mL) compared to selegiline (IC50 of 581.69 ± 11.35 ng/mL). The highest value of the total phenolic content was shown by Angelica sinensis methanolic extract (76.15 ± 0.1mg/g) followed by Glycyrrhiza glabra methanolic extract (65.74 ± 0.1mg/g), then the mixture’s methanolic extract of the four herbs (37.04 ± 0.1mg/g)

The potential preventive effect of dietary phytochemicals In Vivo

Abstract Introduction Chemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea. Aim To evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma. Materials and methods Squamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups. Results The cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups. Conclusions The combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis