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1.
Mol Med ; 29(1): 71, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280507

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on mitochondrial biogenesis in prenatal fetal liver, skeletal muscle, and placental tissues. METHODS: The study was conducted on 20 female albino rats divided into a control group receiving a placebo and an exposed group receiving 4 mg/kg orally/day for 3 months of Sofosbuvir. At the end of the treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle, and placental tissues. RESULTS: The results of our study indicated that the exposure of young female rats to Sofosbuvir affects pregnancy outcomes. Fetal liver and muscle showed lower mitochondrial DNA-copy number (mtDNA-CN) by about 24% and 29% respectively, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and its downstream targets; nuclear respiratory factor-1 and mitochondrial transcription factor A. While the placental tissues showed different patterns, particularly elevated in mtDNA-CN by about 43%. CONCLUSIONS: The study provides preliminary evidence of the detrimental effects of Sofosbuvir on the pregnancy outcomes of the exposed females and may impair the placental and fetal organs' development. These effects may be mediated through modulating mitochondrial homeostasis and functions.


Assuntos
Hepatite C , Sofosbuvir , Humanos , Feminino , Gravidez , Masculino , Ratos , Animais , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Placenta/metabolismo , Exposição Materna/efeitos adversos , Biogênese de Organelas , DNA Mitocondrial/metabolismo , DNA Mitocondrial/farmacologia , Feto , Hepatite C/tratamento farmacológico , Hepatite C/metabolismo , Genótipo
2.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958828

RESUMO

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.


Assuntos
Hepatite C Crônica , Hepatite C , Feminino , Ratos , Animais , Antivirais , Hepatite C Crônica/tratamento farmacológico , Biogênese de Organelas , Resultado do Tratamento , Ratos Wistar , Sofosbuvir/uso terapêutico , Hepatite C/tratamento farmacológico , Hepacivirus/genética , Quimioterapia Combinada , Genótipo
3.
Int J Mol Sci ; 24(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37761983

RESUMO

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.


Assuntos
Hepatite C , Sofosbuvir , Gravidez , Animais , Ratos , Feminino , Humanos , Masculino , Sofosbuvir/farmacologia , Fertilização , Reprodução , Comunicação Celular
4.
Mol Cell Biochem ; 476(5): 2233-2249, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33575874

RESUMO

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. In this study, we investigated the therapeutic effect of different doses of ATX on the cerebral cortex and hippocampus of AD-like rats. The AD-like model was induced in rats using hydrated aluminum chloride (AlCl3.6H2O) solution that was given orally at a dose of 75 mg/kg daily for 6 weeks. Morris water maze (MWM) behavioral test was performed to confirm the cognitive dysfunction then AD-like rats were orally treated with different doses of ATX (5, 10, and 15 mg/kg) dissolved in dimethyl sulfoxide (DMSO) for six weeks. The results indicated that ATX significantly and dose-dependently improved the performance of AD-like rats treated with ATX during MWM and suppress the accumulation of amyloid ß1-42 and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of ß-site amyloid precursor protein cleaving enzyme 1 (BACE 1). ATX also significantly elevated the content of acetylcholine, serotonin, and nuclear factor erythroid-2-related factor 2 (Nrf2) and miRNA-124 expression. The effect of ATX treatment was confirmed by histopathological observations using H&E stain and morphometric tissue analysis. From this study, we concluded that ATX may be a promising therapeutic agent for AD through targeting different pathogenic pathways.


Assuntos
Doença de Alzheimer/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , MicroRNAs/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Hipocampo/patologia , Masculino , Ratos , Xantofilas/farmacologia
5.
J Pediatr Hematol Oncol ; 43(8): e1077-e1081, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33290293

RESUMO

BACKGROUND: Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. OBJECTIVE: The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. METHODOLOGY: A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. RESULTS: Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. CONCLUSIONS: Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , COVID-19/complicações , Neoplasias/virologia , SARS-CoV-2/isolamento & purificação , COVID-19/transmissão , COVID-19/virologia , Criança , Países em Desenvolvimento , Egito/epidemiologia , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/economia , Neoplasias/epidemiologia , Prognóstico , Estudos Prospectivos
6.
BMC Public Health ; 21(1): 1243, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182960

RESUMO

BACKGROUND: Smoking negatively impacts COVID-19 severity and adverse outcomes. Evidence on whether smoking is associated with SARS-Co-V2 infection and having a positive test is scarce, particularly from low-and middle-income countries, where most of the world's billion smokers live. The inconsistency in relevant findings calls for study designs and analyses to account for possible confounders including background characteristics and pre-existing co-morbidities, to disentangle the specific effect of smoking. In healthcare workers (HCWs) the frequency of exposure to COVID-19 cases adds another layer of risk that was not factored in previous studies. We examined the association of HCWs' tobacco/nicotine use (never, former, and current use) with having a positive SARS-Co-V2 test result and symptoms suggestive of infection, accounting for demographics, exposures, and co-morbidities. METHODS: A prospective cohort study of 4040 healthcare workers with baseline and follow-up screening took place during April-June 2020 in 12 healthcare facilities in Cairo, Egypt. Data on demographics, tobacco/nicotine use (manufactured or roll-your-own cigarettes, waterpipe tobacco, and electronic devices), co-morbidities, symptoms, exposures, and SARS-Co-V2 investigations were analyzed. Multinomial and multivariable logistic regression analyses were performed. RESULTS: Overall, 270/4040 (6.7, 95%CI: 5.9-7.5) had positive SARS-CoV-2 tests, 479 (11.9%) were current and 79 (2.0%) were former tobacco/nicotine users. The proportion of positive tests was 7.0% (243/3482, 95%CI: 6.1-7.8) among never, 5.1% (4/79, 95%CI: 0.1-10.0) among former, and 4.8% (23/479, 95%CI: 2.9-6.7) among current users. HCWs' SARS-CoV-2 test results did not vary significantly by single/multiple or daily/non-daily tobacco/nicotine use. Compared to never users, former users were more likely to self-report a pre-existing medical condition (ORadjusted1.87, 95%CI: 1.05-3.33, p = 0.033), and to experience symptoms suggestive of COVID-19 (ORadjusted1.76, 95%CI: 1.07-2.90, p = 0.027). After adjustment, former (ORadjusted0.45, 95%CI: 0.11-1.89, p = 0.273) and current (ORadjusted0.65, 95%CI: 0.38-1.09, p = 0.101) tobacco/nicotine use was not associated with HCWs' SARS-CoV-2 positive test results. CONCLUSIONS: This is the first report on this association from low- and middle-income countries with high tobacco/nicotine use prevalence. In this HCW cohort, having a positive SARS-CoV-2 test was not associated with tobacco/nicotine use after accounting for demographics, exposures, and co-morbidities. Additional population-based studies could use such preliminary evidence to investigate this controversial association.


Assuntos
COVID-19 , Nicotina , Estudos de Coortes , Egito , Pessoal de Saúde , Humanos , Nicotina/efeitos adversos , Estudos Prospectivos , SARS-CoV-2 , Fumar/epidemiologia , Nicotiana
7.
Inorg Chem ; 56(17): 10655-10663, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28832136

RESUMO

The preparation of a binuclear Ni(II) complex with a pentacoordinate environment using a cryptand organic ligand and the imidazolate bridge is reported. The coordination sphere is close to trigonal bipyramidal (tbp) for one Ni(II) and to square pyramidal (spy) for the other. The use of the imidazolate bridge that undergoes π-π stacking with two benzene rings of the chelating ligand induces steric hindrance that stabilizes the pentacoordinate environment. Magnetic measurements together with theoretical studies of the spin states energy levels allow fitting the data and reveal a large Ising-type anisotropy and a weak anti-ferromagnetic exchange coupling between the metal ions. The magnitude and the nature of the magnetic anisotropy and the difference in anisotropy between the two metal ions are rationalized using wave-function-based calculations. We show that a slight distortion of the coordination sphere of Ni(II) from spy to tbp leads to an Ising-type anisotropy. Broken-symmetry density functional calculations rationalize the weak anti-ferromagnetic exchange coupling through the imidazolate bridge.

8.
Inorg Chem ; 56(8): 4602-4609, 2017 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-28375018

RESUMO

The preparations of related mononuclear and binuclear Co(II) complexes with a quasi-identical local C3v symmetry using a cryptand organic ligand are reported. The mononuclear complex behaves as a single molecule magnet (SMM). A relatively weak antiferromagnetic exchange coupling (J) of the same order of magnitude as the local magnetic anisotropy (D) is determined experimentally and theoretically for the binuclear complex. The weak magnitude of the antiferromagnetic exchange coupling, analyzed using a combination of broken-symmetry density functional theory and wave function based calculations, is ascribed to the weak overlap between the singly occupied orbitals because of the local C3v symmetry of the Co(II) ions; the organic ligand was found to contribute to the exchange coupling as the azido bridge that directly links the Co(II) ions. Calculation of the energy and wave functions of the spin states for the binuclear complex, in the general case, allows analysis of the effect of the |J/D| ratio on the magnetic behavior of the binuclear complex and prediction of the optimum range of values for the complex to behave as two weakly interacting SMMs.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124184, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38608556

RESUMO

This research proposes a highly sensitive and simple surface-enhanced Raman spectroscopy (SERS) assay for the detection of SARS-CoV-2 RNA using suitably designed probes specific for RdRp and N viral genes attached to a Raman marker. The sensitivity of the assay was optimized through precise adjustments to the conditions of immobilization and hybridization processes of the target RNA, including modifications to factors such as time and temperature. The assay achieved a remarkable sensitivity down to 58.39 copies/mL, comparable to or lower than the sensitivities reported for commercial fluorescent polymerase chain reaction (PCR) based methods. It has good selectivity in discriminating SARS-CoV-2 RNA against other respiratory viruses, respiratory syncytial virus (RSV), and influenza A virus. The reliability of the assay was validated by testing 24 clinical samples, including 12 positive samples with varying cycle threshold (Ct) values and 12 negative samples previously tested using real-time PCR. The assay consistently predicted true results that were in line with the PCR results for all samples. Furthermore, the assay demonstrated a notable limit of detection (LOD) of Ct (38 for RdRp gene and 37.5 for N-gene), indicating its capability to detect low concentrations of the target analyte and potentially facilitating early detection of the pathogen.


Assuntos
COVID-19 , RNA Viral , SARS-CoV-2 , Análise Espectral Raman , Análise Espectral Raman/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , RNA Viral/genética , RNA Viral/análise , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Inorg Chem ; 52(18): 10264-74, 2013 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-23987215

RESUMO

Based on nickel hexacyanidochromate and cobalt hexacyanidoferrate Prussian blue analogues, two series of photomagnetic/ferromagnetic sub-50 nm core multishell coordination nanoparticles have been synthesized in a surfactant-free one-pot multistep procedure with good control over the dispersity (10% standard deviation) and good agreement with the targeted size at each step. The composition and the valence state of each shell have been probed by different techniques that have revealed the predominance of Co(II)-NC-Fe(III) pairs in a series synthesized without alkali while Co(III)-NC-Fe(II) photoswitchable pairs have been successfully obtained in the photoactive coordination nanoparticles by control of Cs(+) insertion. When compared, the photoinduced behavior of the latter compound is in good agreement with that of the model one. Exchange coupling favors a uniform reversal of the magnetization of the heterostructured nanoparticles, with a large magnetization brought by a soft ferromagnetic shell and a large coercivity due to a harder photomagnetic shell. Moreover, a persistent increase of the photoinduced magnetization is observed for the first time up to the ordering temperature (60 K) of the ferromagnetic component because of a unique synergy.

11.
Eur J Med Res ; 28(1): 317, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660059

RESUMO

BACKGROUND: Opportunistic respiratory infections may complicate critically ill patients with COVID-19. Early detection of co-infections helps to administrate the appropriate antimicrobial agent, to guard against patient deterioration. This study aimed at estimating co-infections in COVID-19-positive patients. METHODS: Eighty-nine COVID-19-positive patients confirmed by SARS-COV-2 PCR were tested for post-COVID-19 lower respiratory tract co-infections through bacterial culture, fungal culture and galactomannan (GM) testing. RESULTS: Fourteen patients showed positive coinfection with Klebsiella, nine with Acinetobacter, six with Pseudomonas and three with E. coli. As for fungal infections, nine showed coinfection with Aspergillus, two with Zygomycetes and four with Candida. Galactomannan was positive among one patient with Aspergillus coinfection, one with Zygomycetes coinfection and three with Candida, 13 samples with negative fungal culture were positive for GM. Ten samples showed positive fungal growth, however, GM test was negative. CONCLUSION: In our study, SARS-COV-2 respiratory coinfections were mainly implicated by bacterial pathogens; most commonly Klebsiella species (spp.), Aspergillus spp. were the most common cause of fungal coinfections, GM test showed low positive predictive value for fungal infection. Respiratory coinfections may complicate SARS-COV-2 probably due to the prolonged intensive care units (ICU) hospitalization, extensive empiric antimicrobial therapy, steroid therapy, mechanical ventilation during the COVID-19 outbreak. Antimicrobial stewardship programs are required so that antibiotics are prescribed judiciously according to the culture results.


Assuntos
COVID-19 , Coinfecção , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Coinfecção/epidemiologia , Escherichia coli , Antibacterianos/uso terapêutico , Candida
12.
Artigo em Inglês | MEDLINE | ID: mdl-36819293

RESUMO

Background: Coronavirus Disease 2019 (COVID-19) pandemic has hit many countries worldwide. Rapid and accurate diagnosis is crucial to reduce disease burden. Many commercial kits have become available, but their performance needs to be assessed. This study aimed at evaluation of the diagnostic performance of real-time polymerase chain reaction (RT-PCR) and Rapid Antigen detection (RAD) kits for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Five hundred sixty-four Nasopharyngeal swab specimens sent to Molecular Laboratory at Ain Shams University Specialized Hospital for SARS-CoV-2 PCR testing collected from 564 subjects who attended the outpatient clinic for sample collection were randomly selected. All samples were tested for SARS-CoV-2 PCR using Viasure. Each time a recent kit was introduced, 94 samples, previously tested using Viasure, were used to determine the performance characteristics of the recent kit in comparison with Viasure, including Fast Track Diagnostics (FTD), DNA Technology, QiaPrep, Xpress SARS-CoV-2, ID NOW COVID-19 assay and Artron COVID-19 Antigen test kit. Results: Upon comparison, FTD, DNA Technology, QiaPrep, Xpress SARS-CoV-2 and ID Now showed positive percent agreement, 100%, 100%, 97.7%, 100%, 100% negative percent agreement, 86%, 100%, 98.8%, 90%, 100%, respectively. The RAD kit results, when compared with RT-PCR, showed high sensitivity at cycle threshold (Ct) < 30, low sensitivity at Ct ≥ 30, while specificity was 100%. Conclusion: Fast track, DNA Technology, QiaPrep, Xpress SARS-CoV-2 and ID Now showed good diagnostic performance. Positive RAD rule in SARS-CoV-2 infection, however negative results should be correlated with clinical condition and molecular testing.

13.
Diabetol Metab Syndr ; 15(1): 33, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36855172

RESUMO

BACKGROUND: Diabetic gastroparesis is a severe diabetic complication refers to delayed gastric emptying in the absence of mechanical obstruction of the stomach. Vitamin B12 affects the dynamics of autonomic nervous system and its deficits has been linked to cardiovascular autonomic neuropathy therefore, vitamin B12 deficiency was hypothesized to be implicated in the development of diabetic gastroparesis. This study was conducted to explore the possible association between vitamin B12 deficiency and gastroparesis in patients with type 2 diabetes (T2D). METHODS: A total of 100 T2D patients with diabetes duration > 10 years and 50 healthy controls matched for age and sex were recruited for this study. T2D patients were divided into 2 groups: patients with gastroparesis and patients without gastroparesis. The diagnosis of gastroparesis was based on Gastroparesis Cardinal Symptom Index (GCSI) Score ≥ 1.9 and ultrasonographic findings including gastric emptying ˂ 35.67% and motility index ˂ 5.1. Anthropometric measurements, plasma glucose, glycosylated hemoglobin (HbA1c), lipids profile, vitamin B12 and transabdominal ultrasonography were assessed. RESULTS: The frequency of vitamin B12 deficiency in total patients with T2D was 35% (54.5% in patients with gastroparesis vs. 11.1% in patients without gastroparesis, P < 0. 001). Vitamin B12 level was negatively correlated with GCSI Score whereas, it was positively correlated with gastric emptying and motility index. Vitamin B12 deficiency was an independent predictor for gastroparesis in patients with T2D; it predicts gastroparesis at a cut off value of 189.5 pmol/L with 69.1% sensitivity and 64.4% specificity, P = 0.002. CONCLUSIONS: Beside the known risk factors of diabetic gastroparesis, vitamin B12 deficiency is an independent predictor of diabetic gastroparesis in patients with T2D.

14.
Nutrients ; 14(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36235591

RESUMO

The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B complex intake. Most studies examined such issues concerning a specific vitamin B or life stage, with the majority reporting the effect of either excess or deficiency. Deep insight into the orchestration of the eight different B vitamins requirements is reviewed across the human life cycle, beginning from fertility and pregnancy and reaching adulthood and senility, emphasizing interactions among them and underlying action mechanisms. The effect of sex is also reviewed for each vitamin at each life stage to highlight the different daily requirements and/or outcomes. Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one's overall health in adolescence and adulthood. A higher intake of B vitamins in the elderly is also associated with preventing some aging problems, especially those related to inflammation. All supplementation should be carefully monitored to avoid toxicity and hypervitaminosis. More research should be invested in studying each vitamin individually concerning nutritional disparities in each life stage, with extensive attention paid to cultural differences and lifestyles.


Assuntos
Niacina , Complexo Vitamínico B , Adolescente , Adulto , Idoso , Criança , Feminino , Ácido Fólico , Humanos , Masculino , Ácido Pantotênico , Gravidez , Piridoxina , Riboflavina , Caracteres Sexuais , Tiamina , Vitamina B 12
15.
Front Mol Biosci ; 9: 817735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350713

RESUMO

The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures.

16.
Genes (Basel) ; 12(6)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071309

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.


Assuntos
COVID-19/genética , COVID-19/virologia , Receptor com Domínio Discoidina 1/genética , Predisposição Genética para Doença , Interferons/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/fisiologia , Metaloproteases Semelhantes a Toloide/genética , Alelos , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , Estudos de Casos e Controles , Comorbidade , Citocinas/metabolismo , Feminino , Genótipo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Masculino , Prognóstico , Índice de Gravidade de Doença , Carga Viral
17.
Int J Infect Dis ; 104: 534-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33484863

RESUMO

BACKGROUND: We examined Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) seroconversion incidence and risk factors 21 days after baseline screening among healthcare workers (HCWs) in a resource-limited setting. METHODS: A prospective cohort study of 4040 HCWs took place at 12 university healthcare facilities in Cairo, Egypt; April-June 2020. Follow-up exposure and clinical data were collected through online survey. SARS-CoV-2 testing was done using rapid IgM and IgG serological tests and reverse transcriptase-polymerase chain reaction (RT-PCR) for those with positive serology. Cox proportional hazards modelling was used to estimate adjusted hazard ratios (HR) of seroconversion. RESULTS: 3870/4040 (95.8%) HCWs tested negative for IgM, IgG and PCR at baseline; 2282 (59.0%) returned for 21-day follow-up. Seroconversion incidence (positive IgM and/or IgG) was 100/2282 (4.4%, 95% CI:3.6-5.3), majority asymptomatic (64.0%); daily hazard of 0.21% (95% CI:0.17-0.25)/48 746 person-days of follow-up. Seroconversion was: 4.0% (64/1596; 95% CI:3.1-5.1) among asymptomatic; 5.3% (36/686; 95% CI:3.7-7.2) among symptomatic HCWs. Seroconversion was independently associated with older age; lower education; contact with a confirmed case >15 min; chronic kidney disease; pregnancy; change/loss of smell; and negatively associated with workplace contact. CONCLUSIONS: Most seroconversions were asymptomatic, emphasizing need for regular universal testing. Seropositivity was three-fold that observed at baseline. Cumulative infections increased nationally by a similar rate, suggesting HCW infections reflect community not nosocomial transmission.


Assuntos
COVID-19/imunologia , Pessoal de Saúde/estatística & dados numéricos , SARS-CoV-2/imunologia , Soroconversão , Centros Médicos Acadêmicos , Adulto , Teste para COVID-19 , Estudos de Coortes , Egito/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Testes Sorológicos , Adulto Jovem
18.
PLoS One ; 16(7): e0254581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265021

RESUMO

BACKGROUND: Research has revealed that asymptomatic and pre-symptomatic infections are important contributors to the transmission of SARS-CoV-2 in populations. In Egypt, the true prevalence of infections is veiled due to the low number of screening tests. The aim of this study was to determine the SARS-CoV-2 PCR positivity rate as well the seroprevalence of the SARS-CoV-2 antibodies before the ultimate development of a second wave of the epidemic in Cairo, Egypt. METHODS: Our study was carried out between May 5 and the end of October 2020. It included all patients requiring admission to Ain Shams University hospitals. An interview questionnaire was used to collect demographic and clinical data. Laboratory tests for all participants included RT-PCR and total antibody assay for SARS-CoV-2. RESULTS: A total of 4,313 subjects were enrolled in our study, with females representing 56% of the sample. Adults and middle-aged individuals represented around 60% of the study sample. The positivity rate of SARS-CoV-2 PCR was 3.84% (95% CI 3.29-4.48), and the SARS-CoV-2 antibody seroprevalence was 29.82% (95% CI: 28.16-31.51). Males showed a higher risk for getting the COVID-19 infection, while middle-age group had significantly higher antibody seroprevalence rates. CONCLUSION: SARS-CoV-2 infection imposes a high burden on the community as detected by high seroprevalence rates.


Assuntos
Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Teste Sorológico para COVID-19/estatística & dados numéricos , COVID-19/epidemiologia , Adolescente , Adulto , COVID-19/diagnóstico , Egito , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
19.
Int J Epidemiol ; 50(1): 50-61, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33094320

RESUMO

BACKGROUND: The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs), particularly in resource-limited settings, remains unclear. To address this concern, universal (non-symptom-based) screening of HCWs was piloted to determine the proportion of SARS-CoV-2 infection and the associated epidemiological and clinical risk factors at a large public health care facility in Egypt. METHODS: Baseline voluntary screening of 4040 HCWs took place between 22 April and 14 May 2020 at 12 hospitals and medical centres in Cairo. Epidemiological and clinical data were collected using an online survey. All participants were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) and rapid IgM and IgG serological tests. RESULTS: Of the 4040 HCWs screened, 170 [4.2%; 95% confidence interval (CI): 3.6-4.9] tested positive for SARS-CoV-2 by either of the three tests (i.e. infected); 125/170 (73.5%) tested PCR-positive. Most infected HCWs were nurses (97/170, 57.5%). Median age of infected HCWs was 31.5 [interquartile range (IQR): 27.0-41.3] years. Of infected HCWs, 78 (45.9%) reported contact with a suspected case and 47 (27.6%) reported face-to-face contact within 2 m with a confirmed case. The proportion of infection among symptomatic HCWs (n = 54/616) was 8.8% (95% CI: 6.7-11.3); 6/54 (11.1%) had fever ≥38°C and 7/54 (13.0%) reported severe symptoms. Most infected HCWs were asymptomatic (116/170, 68.2%). The proportion of infection among asymptomatic HCWs (n = 116/3424) was 3.4% (95% CI: 2.8-4.0). CONCLUSIONS: The high rate of asymptomatic infections among HCWs reinforces the need for expanding universal regular testing. The infection rate among symptomatic HCWs in this study is comparable with the national rate detected through symptom-based testing. This suggests that infections among HCWs may reflect community rather than nosocomial transmission during the early phase of the COVID-19 epidemic in Egypt.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Pessoal de Saúde/psicologia , Programas de Rastreamento/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Atenção Terciária à Saúde/estatística & dados numéricos , Adulto , Doenças Assintomáticas , COVID-19/epidemiologia , COVID-19/virologia , Egito/epidemiologia , Feminino , Febre/virologia , Hospitais Universitários , Humanos , Controle de Infecções/organização & administração , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , SARS-CoV-2/genética , Atenção Terciária à Saúde/organização & administração
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