Insight into brain sex differences of typically developed infants and brain pathologies: A systematic review.

The continually advancing landscape of neuroscientific and imaging research has broadened our comprehension of sex differences encoded in the human brain, expanding from the hypothalamus and sexual behaviour to encompass the entire brain, including its diverse lobes, structures, and functions. However, less is known about sex differences in the brains of neonates and infants, despite their relevance to various sex-linked diseases that develop early in life. In this review, we provide a synopsis of the literature evidence on sex differences in the brains of neonates and infants at the morphological, structural and network levels. We also briefly overview the present evidence on the sex bias in some brain disorders affecting infants and neonates.

Nanoscale potassium sensing based on valinomycin-anchored fluorescent gold nanoclusters.

Gold nanoclusters are a smart platform for sensing potassium ions (K+). They have been synthesized using bovine serum albumin (BSA) and valinomycin (Val) to protect and cap the nanoclusters. The nanoclusters (Val-AuNCs) produced have a red emission at 616 nm under excitation with 470 nm. In the presence of K+, the valinomycin polar groups switch to the molecule's interior by complexing with K+, forming a bracelet structure, and being surrounded by the hydrophobic exterior conformation. This structure allows a proposed fluorometric method for detecting K+ by switching between the Val-AuNCs' hydrophilicity and hydrophobicity, which induces the aggregation of gold nanoclusters. As a result, significant quenching is seen in fluorescence after adding K+. The quenching in fluorescence in the presence of K+ is attributed to the aggregation mechanism. This sensing technique provides a highly precise and selective sensing method for K+ in the range 0.78 to 8 µM with LOD equal to 233 nM. The selectivity of Val-AuNCs toward K+ ions was investigated compared to other ions. Furthermore, the Val-AuNCs have novel possibilities as favorable sensor candidates for various imaging applications. Our detection technique was validated by determining K+ ions in postmortem vitreous humor samples, which yielded promising results.

Effect of CYP2D6, 2C19, and 3A4 Phenoconversion in Drug-Related Deaths.

Molecular autopsy is a very important tool in forensic toxicology. However, many determinants, such as co-medication and physiological parameters, should be considered for optimal results. These determinants could cause phenoconversion (PC), a discrepancy between the real metabolic profile after phenoconversion and the phenotype determined by the genotype. This study's objective was to assess the PC of drug-metabolizing enzymes, namely CYP2D6, 2C19, and 3A4, in 45 post-mortem cases where medications that are substrates, inducers, or inhibitors of these enzymes were detected. It also intended to evaluate how PC affected the drug's metabolic ratio (MR) in four cases. Blood samples from 45 cases of drug-related deaths were analyzed to detect and determine drug and metabolite concentrations. Moreover, all the samples underwent genotyping utilizing the HaloPlex Target Enrichment System for CYP2D6, 2C19, and 3A4. The results of the present study revealed a statistically significant rate of PC for the three investigated enzymes, with a higher frequency of poor metabolizers after PC. A compatibility was seen between the results of the genomic evaluation after PC and the observed MRs of venlafaxine, citalopram, and fentanyl. This leads us to focus on the determinants causing PC that may be mainly induced by drug interactions. This complex phenomenon can have a significant impact on the analysis, interpretation of genotypes, and accurate conclusions in forensic toxicology. Nevertheless, more research with more cases in the future is needed to confirm these results.

Biosynthesis Strategy of Gold Nanoparticles and Biofabrication of a Novel Amoxicillin Gold Nanodrug to Overcome the Resistance of Multidrug-Resistant Bacterial Pathogens MRSA and E. coli.

The prevalence of multidrug-resistant (MDR) bacteria has recently increased dramatically, seriously endangering human health. Herein, amoxicillin (Amoxi)-conjugated gold nanoparticles (AuNPs) were created as a novel drug delivery system to overcome MDR bacteria. MDR bacteria were isolated from a variety of infection sources. Phenotype, biotype, and 16S rRNA gene analyses were used for isolate identification. Additionally, Juniperus excelsa was used for the production of AuNPs. The conjugation of AuNPs with Amoxi using sodium tri-polyphosphate (TPP) as a linker to produce Amoxi-TPP-AuNPs was studied. The AuNP and Amoxi-TPP-AuNP diameters ranged from 15.99 to 24.71 nm, with spherical and hexagonal shapes. A total of 83% of amoxicillin was released from Amoxi-TPP-AuNPs after 12 h, and after 3 days, 90% of the medication was released. The Amoxi-TPP-AuNPs exhibited superior antibacterial effectiveness against MRSA and MDR E. coli strains. Amoxi-TPP-AuNPs had MICs of 3.6-8 µg mL-1 against the tested bacteria. This is 37.5-83 fold higher compared to values reported in the literature. Amoxi-TPP-AuNPs exhibit a remarkable ability against MRSA and E. coli strains. These results demonstrate the applicability of Amoxi-TPP-AuNPs as a drug delivery system to improve therapeutic action.

Cakes fortified with papaya seeds effectively protects against CCl4-induced immunotoxicity.

Maintaining a robust immune system and safeguarding the liver from toxins are crucial for overall health. The study aimed to investigate the immunostimulant effects of papaya seed-enriched cakes (CPS) in countering carbon tetrachloride (CCl4)-induced immunocytotoxicity in rats (n = 48). The rats were divided into six groups (8 each): a control group (Group 1), rats fed cakes containing 15% papaya seeds (Group 2 - CPS), rats exposed only to CCl4 (Group 3 - CCl4), rats injected with CCl4 and administered silymarin (Group 4 - CCl4 + S), rats receiving both CCl4 and cakes with papaya seeds (Group 5 - CCl4 + CPS), and rats receiving both CCl4 and silymarin with papaya seed-enriched cakes (Group 6 - CCl4 + CPS + S). HPLC analysis of papaya seeds revealed the presence of ten polyphenol compounds, with quercetin, apigenin, and catechin identified as major flavonoids, along with pyrogallol, ellagic, and gallic acid as predominant phenolic acids. These compounds displayed potent antioxidant activity, attributed to the seeds' high total phenolic and flavonoid content. The administration of CCl4 significantly affected hematological parameters, liver enzymes, hepatic oxidative stress, levels of TNF-α, IL-6, IgG, as well as IgM. However, rats fed with CPS exhibited mitigation of CCl4-induced toxic effects on hematological parameters and hepatotoxicity. CPS consumption enhanced the antioxidant system, improved inflammatory markers, and immune parameters, restoring them to normal levels. Histopathological analysis confirmed CPS's ability to reduce CCl4-induced hepatocellular necrosis. Immunohistochemical assessment further revealed reduced immunoreactivity against cleaved caspase-3 expression and increased COX2 immunoreactivity, indicating hepatocellular regeneration in CPS. The combination of CPS and silymarin demonstrated even more notable improvements, suggesting augmented protective impacts against CCl4-induced immunosuppression and hepatotoxicity. In conclusion, CPS exhibited antioxidant properties and effectively protected against CCl4-induced immunotoxicity and hepatotoxicity, with additional benefits observed when combined with silymarin. These findings emphasize the potential health advantages of incorporating papaya seeds into food products, promoting immune system health, and safeguarding against liver damage induced by hazardous agents like CCl4.

Multidrug resistant and multivirulent avian bacterial pathogens: tackling experimental leg disorders using phytobiotics and antibiotics alone or in combination.

Locomotor disorders caused by multidrug-resistant (MDR) bacterial pathogens denote one of the most detrimental issues that collectively threaten the poultry industry leading to pronounced economic losses across the world. Hence, searching for effective alternatives, especially those extracted from plant origins became of great priority targeting a partial or complete replacement of chemical antimicrobials to tackle their developing resistance. Therefore, we aimed to determine the prevalence and antimicrobial resistance of Staphylococcus aureus (S. aureus), Salmonella species, Mycoplasma synoviae (M. synoviae), and Escherichia coli (E. coli) recovered from 500 broilers and ducks (250 each) with locomotor disorders in various farms in Dakahlia and Sharkia Governorates, Egypt. Additionally, we assessed, for the first time, the in vitro antimicrobial effectiveness of marjoram, garlic, ginger and cinnamon essential oils (EOs) against MDR and multivirulent bacterial isolates as well as the in vivo efficiency of the most effective antibiotics and EOs either separately or in combination in the treatment of experimentally induced poultry leg disorders. The overall prevalence rates of S. aureus, E. coli, Salmonella species, and M. synoviae were 54, 48, 36, and 2%, respectively. Salmonella species and S. aureus prevailed among ducks and broilers (36 and 76%, respectively). Notably, MDR was observed in 100, 91.7, 81.1, and 78.5% of M. synoviae, E. coli, Salmonella, and S. aureus isolates, respectively. Our in vitro results displayed that marjoram was the most forceful EO against MDR and multivirulent chicken vancomycin-resistant S. aureus (VRSA) and duck S. Typhimurium isolates. The current in vivo results declared that marjoram in combination with florfenicol or amoxicillin/clavulanic acid succeeded in relieving the induced duck and chicken leg disorders caused by S. Typhimurium and VRSA, respectively. This was evidenced by improvement in the clinical and histopathological pictures with a reduction of bacterial loads in the experimental birds. Our encountered successful in vitro and in vivo synergistic effectiveness of marjoram combined with florfenicol or amoxicillin/clavulanic acid recommends their therapeutic application for leg disorders and offers opportunities for reducing the antibiotics usage in the poultry industry.

Biofabrication strategy of silver-nanodrug conjugated polyhydroxybutyrate degrading probiotic and its application as a novel wound dressing.

Wound infections with rising incidences of multi-drug resistant bacteria are among the public health problems worldwide. The current study describes wound dressing materials made from biodegradable polyhydroxybutyrate (PHB) combined with AgNPs and gelatin (AgNPs/Gelatin/PHB). Microbial PHB was mixed with gelatin (1:2) to form a polymer matrix which was loaded with different concentrations of AgNPs (8.3-133 µg/mL). The statistical results of AgNPs synthesizing based on Box-Behnken design revealed that 1.247 mM silver nitrate and 24.054 % of Corchorus olitorius leaf extract concentration at pH (8.07) were the optimum values for the biosynthesis. UV-Vis spectroscopy, FTIR study and XRD reflects that nanoparticles are formed. The UV-Vis spectroscopy of Gelatin/PHB/AgNPs exhibited two specific bands at 298 nm and 371 nm, which confirm the formation of the conjugate. AgNPs had MICs and MBCs of (24.9, 24.9, and 12.45 µg/mL) and (33.25, 33.25, and 16.6 µg/mL) against (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). The MIC and MBC of AgNPs/Gelatin/PHB against the same tested bacteria were 31.1 µg and 41.5 µg, respectively. AgNPs/Gelatin/PHB exhibit excellent antimicrobial efficacy against bacteria. Sterilized gauze loaded with 31.1 µg of AgNPs/Gelatin/PHB acted as an effective wound dressing. Thus, the study highlights the importance of wound dressings developed from degradable AgNPs/Gelatin/PHB in enhancing antimicrobial efficiency and facilitating a better wound healing process.

Lead, Mercury, and Cadmium Concentrations in Blood Products Transfused to Neonates: Elimination Not Just Mitigation.

Lead (Pb), mercury (Hg), and cadmium (Cd) are identified as potent developmental neurotoxicants. Neonates are the main group receiving multiple blood transfusions. The exposure of neonates to these heavy metals (HMs) can occur through blood transfusions. This study aimed to determine the concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in various blood products (plasma, platelets, packed red blood cells (pRBCs), and whole blood (WB)) to explore the probability of concurrent exposure of these HMs and to identify the metal load per transfusion with risk assessment. Residual bloods from blood bank bags were collected after neonatal transfusion. Pb, Hg, and Cd concentrations were determined in 120 samples of blood products by inductively coupled plasma mass spectrometry (ICP-MS). Pb and Cd levels were over the normal levels in 19.2 and 5.9% of all blood units, respectively. In 35 and 0.8% of blood units, the Pb and Cd concentrations, respectively, were higher than that recommended for transfusions in premature neonates. The anticipated safe value was surpassed by 2.5% for Cd of all transfusions, primarily because of WB. However, Hg was detected only in 5.8% of all samples and their concentrations were within the normal range. The concurrent neonatal exposure to Pb, Hg, and Cd was statistically significant. Hazard quotients of Hg and Cr were >1 and Pb cancer risk was 2.41 × 10-4. To the best of our knowledge, this study is the first report examining Pb, Hg, and Cd in blood products other than WB and pRBCs using ICP-MS. This study demonstrated the exposure of neonates to Pb, Hg, and Cd during transfusion with a considerable amount of Pb. It confirms the significant concurrent exposure to the three HMs, which maximize their potential developmental neurotoxicity with a high probability of developing non-carcinogenic and carcinogenic health effects.

Metabolic ratios and SNPs implicated in tramadol-related deaths.

Tramadol (TR) metabolism is performed by polymorphic enzymes that are influenced by genetic polymorphisms. Within this scope, the study presented here aimed to describe 41 genetic variants within CYP2D6, CYP2B6, and CYP3A4 genes in 48 cases of TR-related death that may be involved in the response to TR and to assess whether there is a correlation between these genetic variants and metabolic ratios (MRs). Blood samples from 48 victims of a TR-related death were analyzed to determine the concentrations of TR and its metabolites [O-desmethyltramadol (M1) & N-desmethyltramadol (M2)] using a LC-MS/MS method. All the samples were also genotyped for 41 common CYP2D6, CYP2B6, and CYP3A4 single nucleotide polymorphisms (SNPs) using the HaloPlex Target Enrichment system. Cases with the T/- genotype (rs35742686 in CYP2D6) had significantly higher M2/M1 ratio than cases with T/T genotype and cases with the G/A genotype (rs35599367 in CYP3A4) had significantly higher MR2 (TR/M2) ratio than cases with G/G genotype. The frequency of tested SNPs which belong to CYP2D6, CYP2B6, and CYP3A4 revealed the over-presentation of 2 SNPs (rs1058172 in CYP2D6 and rs4803419 in CYP2B6) in TR overdose group, which could have toxicological implications. These results indicate these polymorphisms in CYP2D6, CYP2B6, and CYP3A4 might influence the function and could increase the risk of toxicity. However, these findings should be supported in future studies with larger groups of cases.

Sexual Harassment: Knowledge, Prevalence, Pattern, and Impacts Among Egyptian Female College Students.

Sexual harassment (SH) is an uprising problem worldwide, especially in Egypt. This study aims to determine the magnitude, patterns, and circumstances of SH among female students at Suez Canal University. A cross-sectional study was conducted on a representative female student sample (N = 644) from all the faculties using a self-administered anonymous questionnaire. The high prevalence of SH among college students in this study could be a consequence of the absence of knowledge about the legal framework. It mostly happened at all times of the day and night in the streets, and the least amount happened on the campus. Most of the harassers were younger than 20 years old and strangers. The majority of harassed females and surrounding people displayed negative reactions. None of the harassed females notified the authorities. The majority blamed men, and half claimed the SH act was due to the absence of religious principles. Moreover, the ignorance of the majority is with Egyptian law against SH. Both psychological and social impacts are significantly experienced by the harassed females. Thus, it is urgent to establish an institutional program (e.g., psycho-educative sessions during classes and peer training) or national awareness campaigns. Such programs and trainings aim to increase the awareness of students about the SH legal framework and how to deal with such acts, either as a victim or a witness, and how to provide the needed psychological assistance.

Mesenchymal Stem Cells and Myeloid-Derived Suppressor Cells Interplay in Adjuvant-Induced Arthritis Rat Model.

There has not been much researchs on the biological relationship between myeloid-derived suppressor cells (MDSCs) and mesenchymal stem cells (MSCs). The goal of the current work is to examine how these cells cooperate with one another in a rat model of adjuvant-induced arthritis (AIA). Three groups of equal numbers of rats were created; the first group served as the control. Complete Freund's adjuvant (CFA) was injected into the second group to induce AIA. The third group underwent MSCstreatment. Three weeks later, ANA, IL-1ß, IL-4, IL-6, IL-10, TNF-α, IFN-γ, M-CSF, iNOS and Arg-1 were determined using ELISA. Flowcytometric studies for MDSCs using CD11bc + and His48 + antibodies were performed. Current results showed significantly higher levels of WBCs, ANA, IL-1, IL-4, IL-6, IL-10, TNF-α, M-CSF, iNOS and Arg-1 along with a significant rise in MDSCs % in the AIA group compared to the control group. As opposed to AIA animals, MSCs administration resulted in a considerable improvement in cytokine levels, supporting the immunomodulation function of MSCs. Histological examination of the joints in the AIA group revealed articular cartilage degradation as well as infiltration of inflammatory cells and fibroplasia. These several evidences suggested that MDSCs may perform various roles in autoimmunity. Understanding how MDSCs and MSCs contribute to arthritis may help their prospective application in immunotherapy. Therefore, the reciprocal collaboration of MSCs and MDSCs must therefore be the subject of new investigations, which can offer new platforms for the development of more effective and individualized therapies for the treatment of immunological illnesses.

Bivalent Metal Chelates with Pentadentate Azo-Schiff Base Derived from Nicotinic Hydrazide: Preparation, Structural Elucidation, and Pharmacological Activity.

Azo-Schiff base ligand (N'-((E)-2-hydroxy-5-((E)-(2-hydroxyphenyl)diazenyl)benzylidene)nicotinohydrazide) and its Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) chelates were prepared and elucidated. The geometrical structures of the prepared chelates were characterized by several spectroanalytical techniques and thermogravimetric analysis. The obtained data revealed that the chelates have (1M:1L), (1M:2L), (1M:3L), and (1M:4L) molar ratios. The infrared spectra displayed that the H2 L ligand behaves in a pentacoordinate fashion in chelates of Mn(II), Ni(II), and Cu(II) ions. However, in Zn(II) and Pd(II) chelates, the ligand is coordinated as a tetradentate species (NONO) through nitrogen atoms of azomethine and azo groups as well as oxygen atoms of phenolic hydroxy, and carbonyl groups. Besides, it was concluded that the oxygen atoms of carbonyl and hydroxy groups along with the azomethine nitrogen atom of the ligand are bounded with Co(II) ion in metal chelate (2). According to the measured molar conductance values, the chelates of Cu(II), Zn(II), and Pd(II) are weak electrolytes, but Mn(II), Co(II), and Ni(II) chelates are ionic. The azo-Schiff base ligand and its prepared metal chelates were tested for their antioxidant and antibacterial properties. The Ni(II) chelate was found to be considered an effective antioxidant agent. In addition, the available antibacterial data suggest that the Ni(II) and Co(II) chelates may be employed as inhibitor agents against Proteus vulgaris, Escherichia coli, and Bacillus subtilis bacteria. Furthermore, the data showed that, in comparison to the ligand and other metal chelates, copper(II) chelate (4) exhibited higher action against Bacillus subtilis bacteria.

Hesperetin and Capecitabine Abate 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis in Wistar Rats via Suppressing Oxidative Stress and Enhancing Antioxidant, Anti-Inflammatory and Apoptotic Actions.

Colon cancer is a major cause of cancer-related death, with significantly increasing rates of incidence worldwide. The current study was designed to evaluate the anti-carcinogenic effects of hesperetin (HES) alone and in combination with capecitabine (CAP) on 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. The rats were given DMH at 20 mg/kg body weight (b.w.)/week for 12 weeks and were orally treated with HES (25 mg/kg b.w.) and/or CAP (200 mg/kg b.w.) every other day for 8 weeks. The DMH-administered rats exhibited colon-mucosal hyperplastic polyps, the formation of new glandular units and cancerous epithelial cells. These histological changes were associated with the significant upregulation of colon Ki67 expression and the elevation of the tumor marker, carcinoembryonic antigen (CEA), in the sera. The treatment of the DMH-administered rats with HES and/or CAP prevented these histological cancerous changes concomitantly with the decrease in colon-Ki67 expression and serum-CEA levels. The results also indicated that the treatments with HES and/or CAP showed a significant reduction in the serum levels of lipid peroxides, an elevation in the serum levels of reduced glutathione, and the enhancement of the activities of colon-tissue superoxide dismutase, glutathione reductase and glutathione-S-transferase. Additionally, the results showed an increase in the mRNA expressions of the anti-inflammatory cytokine, IL-4, as well as the proapoptotic protein, p53, in the colon tissues of the DMH-administered rats treated with HES and/or CAP. The TGF-ß1 decreased significantly in the DMH-administered rats and this effect was counteracted by the treatments with HES and/or CAP. Based on these findings, it can be suggested that both HES and CAP, singly or in combination, have the potential to exert chemopreventive effects against DMH-induced colon carcinogenesis via the suppression of oxidative stress, the stimulation of the antioxidant defense system, the attenuation of inflammatory effects, the reduction in cell proliferation and the enhancement of apoptosis.

Assessment of Bioactive Phytochemicals and Utilization of Rosa canina Fruit Extract as a Novel Natural Antioxidant for Mayonnaise.

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g-1), total flavonoids content (26.31 ± 1.03 mg QE g-1), and free radical scavenging activity. The GC-MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods.

In the case of extensively putrefied bodies, the analysis of entomological samples may support and complement the toxicological results obtained with other alternative matrices.

Entomotoxicological analysis is not part of routine toxicological analysis. This work aims to present two cases to illustrate the potential of entomological samples as complementary matrices to identify substances in cases of advanced putrefaction. (Case#1) A woman wasexhumed after 14 months to ascertain the exact cause of death. She died after six weeks of hospitalization because of intestinal ischemia followed by multiorgan failure. (Case#2) The corpse of a woman, known to have a psychiatric disorder, was discovered in her apartment. The state of decomposition of the body was consistent with a post-mortem period of several weeks (approximately 6 weeks). Toxicological investigations were performed in the biological and entomological samples of case#1 (hair, adipocere, brain, and pupae) and of case#2 (hair, bone, flies, and pupae) using liquid chromatography with high-resolution mass spectrometry and tandem mass spectrometry detection methods. In case#1, several drugs and metabolites were detected. In particular, the pupae analyses allowed the objectification of morphine administration, whereas morphine was only found in adipocere, but not in hair nor in brain. In case#2, the pupae analyses allowed the detection of three metabolites of quetiapine, and the flies analyses allowed the detection of valpromide, which was only detected in hair. In conclusion, the pupae and flies analyses in these two cases complemented the results obtained in the other alternative biological samples, which may guide hypotheses about the possible causes of death. Nevertheless, additional data and case reports would be of benefit to assess the value of entomotoxicology in routine forensic investigations.

A multi-country phase 2 study to evaluate the suitcase lab for rapid detection of SARS-CoV-2 in seven Sub-Saharan African countries: Lessons from the field.

BACKGROUND: The COVID-19 pandemic led to severe health systems collapse, as well as logistics and supply delivery shortages across sectors. Delivery of PCR related healthcare supplies continue to be hindered. There is the need for a rapid and accessible SARS-CoV-2 molecular detection method in low resource settings. OBJECTIVES: To validate a novel isothermal amplification method for rapid detection of SARS-CoV-2 across seven sub-Sharan African countries. STUDY DESIGN: In this multi-country phase 2 diagnostic study, 3,231 clinical samples in seven African sites were tested with two reverse transcription Recombinase-Aided Amplification (RT-RAA) assays (based on SARS-CoV-2 Nucleocapsid (N) gene and RNA-dependent RNA polymerase (RdRP) gene). The test was performed in a mobile suitcase laboratory within 15 min. All results were compared to a real-time RT-PCR assay. Extraction kits based on silica gel or magnetic beads were applied. RESULTS: Four sites demonstrated good to excellent agreement, while three sites showed fair to moderate results. The RdRP gene assay exhibited an overall PPV of 0.92 and a NPV of 0.88. The N gene assay exhibited an overall PPV of 0.93 and a NPV 0.88. The sensitivity of both RT-RAA assays varied depending on the sample Ct values. When comparing sensitivity between sites, values differed considerably. For high viral load samples, the RT-RAA assay sensitivity ranges were between 60.5 and 100% (RdRP assay) and 25 and 98.6 (N assay). CONCLUSION: Overall, the RdRP based RT-RAA test showed the best assay accuracy. This study highlights the challenges of implementing rapid molecular assays in field conditions. Factors that are important for successful deployment across countries include the implementation of standardized operation procedures, in-person continuous training for staff, and enhanced quality control measures.

The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study.

To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study's endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2-4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28-32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses.

Development and Validation of a Red Flag Prediction Model for Admission of COVID-19 Patients to the Intensive Care Unit.

We aimed to develop and validate a model for the criteria for admission of COVID-19 patients to the intensive care unit (ICU). A Delphi design study was conducted. The content validity index (CVI) was used to determine the degree of agreement among the experts to validate the content of the admission criteria tool. Eleven experts determined the validity. The evaluation was conducted using a 4-point rating scale. The accepted CVI value was 0.50 and more. The model was validated with 31 items in the 5 dimensions, with the item-CVI of 1, a face validity index of 1, and a scale-level content validity index (S-CVI) value of 1. We have developed and validated a red flag prediction model for ICU admission of COVID-19 patients. The accurate implementation of this model could improve the outcomes of those patients and possibly decrease mortality.

Enhancement of active ingredients and biological activities of Nostoc linckia biomass cultivated under modified BG-110 medium composition.

The current work aims to investigate the effect of abiotic stresses (nitrogen (N) and sulfur (S) [0.0 g/l, 1.5 g/l, 3 g/l, 6 g/l, and 12 g/l N and 0.0 g/l, 0.07 g/l, 0.15 g/l, 0.3 g/l, and 0.6 g/l S] and their combination [0.3 g/l S + 6 g/l N]) of axenic culture of Nostoc linckia on the production of secondary metabolites which induce different biological activities. Growth rate was measured by dry weight (DW) and optical density (OD)550 nm. Additionally, phytochemical compounds, defense enzymes as well as antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(ethylbenzthiazoline-6-sulfonic acid) (ABTS·+) radical assays of crude extracts (methylene chloride:methanol, 1:1) were evaluated. Based on antioxidant activity, four promising extracts were subjected to different biological activities such as anticancer, antimicrobial, and antiviral activities. The obtained results revealed that supplementation of external nitrogen source in the form of sodium nitrate was found to increase the total phycobiliprotein content by fivefold. Also, nitrogen depletion provoked significantly highest quantities of phenolic and flavonoid content and this has effects on biological activities of Nostoc linckia. Moreover, 0.3 g/l S was found to be the most effective extract exhibiting a significant increase in antioxidant activity based on DPPH and ABTS assays, respectively (88.18 ± 0.64% and 84.20 ± 1.01%). Furthermore, it recorded anticancer activity against HCT 116 cell line with IC50 of 155 µg/ml. Moreover, this extract possessed a noticeable antibacterial potency (21.0 ± 1.0 as mm inhibition zone against Staphylococcus aureus and 19.3 ± 0.6 against Streptococcus mutans). In addition, its antiviral activity against H5N1 virus as a percentage of inhibition was 50% and 63.6% at a concentration of 7 µg/ml and 28 µg/ml, respectively, with cytotoxicity less than 7 µg/µl. GC-MS analysis recorded the presence of bioactive compounds exhibiting different biological activities. Therefore, the obtained results can represent valuable bioactive compounds with variable biological potencies.