Publications by authors named "Mohamed Badr"

60 Publications

Thiazolidine-2,4-dione-linked ciprofloxacin derivatives with broad-spectrum antibacterial, MRSA and topoisomerase inhibitory activities.

Mol Divers 2021 Aug 29. Epub 2021 Aug 29.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.

A series of ciprofloxacin/thiazolidine-2,4-dione hybrids 3a-m were prepared and identified by IR, HNMR, CNMR and elemental analysis. The antibacterial activity results of the designed hybrids revealed a shift of spectrum toward Gram-positive bacteria. They exhibited excellent activity against S. aureus ATCC 6538, with the most potent compounds being 3a, 3e, 3g, 3i, 3k, 3l and 3m possessing MICs of 0.02, 2.03, 0.64, 0.35, 1.04, 0.22 and 0.36 µM, respectively, compared to their parent compound ciprofloxacin (MIC: 5.49 µM). They also showed interesting activity against MRSA AUMC 261 with 3a, 3e and 3l showing MIC values of 5 nM. Reduced activity was observed against Gram-negative bacteria with compound 3l exhibiting a slightly higher activity against K. pneumoniae ATCC10031 with a MIC value of 0. 08 µM. Mechanistically, the incorporation of thiazolidine-2,4-dione ring into ciprofloxacin retained its ability to inhibit DNA synthesis via inhibiting both topoisomerase IV and DNA gyrase of S. aureus. Compounds 3a, 3l and 3m were more potent than ciprofloxacin for topoisomerase IV (IC = 0.3-1.9 μM) and gyrase (IC = 0.22-0.31 µM) inhibition, which coincide with their antibacterial activity against S. aureus ATCC 6538. Docking against DNA gyrase active site confirmed the ability of the tested compounds to form stable complexes with the enzyme; like that of ciprofloxacin, 3a, 3i, 3k, 3m and 3l reconsidered promising broad-spectrum antibacterial agents targeting topoisomerase IV and gyrase enzymes and have good activity against MRSA.
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http://dx.doi.org/10.1007/s11030-021-10302-7DOI Listing
August 2021

Central venous-to-arterial PCO difference as a marker to identify fluid responsiveness in septic shock.

Sci Rep 2021 08 26;11(1):17256. Epub 2021 Aug 26.

Department of Critical Care Medicine, Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.

Defining the hemodynamic response to volume therapy is integral to managing critically ill patients with acute circulatory failure, especially in the absence of cardiac index (CI) measurement. This study aimed at investigating whether changes in central venous-to-arterial CO difference (Δ-ΔPCO) and central venous oxygen saturation (ΔScvO) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness in sedated and mechanically ventilated septic patients. We prospectively studied 49 critically ill septic patients in whom VE was indicated because of circulatory failure and clinical indices. CI, ΔPCO, ScvO, and oxygen consumption (VO) were measured before and after VE. Responders were defined as patients with a > 10% increase in CI (transpulmonary thermodilution) after VE. We calculated areas under the receiver operating characteristic curves (AUCs) for Δ-ΔPCO, ΔScvO, and changes in CI (ΔCI) after VE in the whole population and in the subgroup of patients with an increase in VO (ΔVO) ≤ 10% after VE (oxygen-supply independency). Twenty-five patients were fluid responders. In the whole population, Δ-ΔPCO and ΔScvO were significantly correlated with ΔCI after VE (r =  - 0.30, p = 0.03 and r = 0.42, p = 0.003, respectively). The AUCs for Δ-ΔPCO and ΔScvO to define fluid responsiveness (increase in CI > 10% after VE) were 0.76 (p < 0.001) and 0.68 (p = 0.02), respectively. In patients with ΔVO ≤ 10% (n = 36) after VE, the correlation between ΔScvO and ΔCI was 0.62 (p < 0.001), and between Δ-ΔPCO and ΔCI was - 0.47 (p = 0.004). The AUCs for Δ-ΔPCO and ΔScvO were 0.83 (p < 0.001) and 0.73 (p = 0.006), respectively. In these patients, Δ-ΔPCO ≤ -37.5% after VE allowed the categorization between responders and non-responders with a positive predictive value of 100% and a negative predictive value of 60%. In sedated and mechanically ventilated septic patients with no signs of tissue hypoxia (oxygen-supply independency), Δ-ΔPCO is a reliable parameter to define fluid responsiveness.
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http://dx.doi.org/10.1038/s41598-021-96806-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390642PMC
August 2021

The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression.

Cell Death Dis 2021 07 5;12(7):675. Epub 2021 Jul 5.

Institute of Medical Microbiology and Hygiene, Medical Center - University of Freiburg, Faculty of Medicine, 79104, Freiburg, Germany.

Mutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.
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http://dx.doi.org/10.1038/s41419-021-03948-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257693PMC
July 2021

Effect of National Early Warning Scoring System Implementation on Cardiopulmonary Arrest, Unplanned ICU Admission, Emergency Surgery, and Acute Kidney Injury in an Emergency Hospital, Egypt.

J Multidiscip Healthc 2021 15;14:1431-1442. Epub 2021 Jun 15.

Anesthesia and Critical Care, Faculty of Medicine, Cairo University, Cairo, Egypt.

Purpose: To evaluate the effect of national early warning scoring system (NEWS) implementation in identifying patients at risk of clinical deterioration at an emergency hospital.

Background: Early warning score has been developed to facilitate early detection of deterioration by categorizing a patients' severity of illness and prompting nursing staff to request a medical review at specific trigger points.

Patients And Methods: A prospective, control/intervention groups', quasi-experimental design was utilized. A sample of 364 adult patients were admitted to the inpatient unit at an emergency hospital for six months. The patients were divided into a study group (174 patients) and a control group (190 patients). All study patients were followed up to either death or hospital discharge before and after implementing a new observation chart. The patients' outcomes were compared and analyzed between both groups.

Results: In the intervention period, compared to the control period, a significant reduction was seen in the number of cardiopulmonary arrest (4.7% vs 1.1%, p = 0.046), unplanned ICU admission (5.3% vs 1.7%, p = 0.049), emergency surgery (6.3% vs 0%, p = 0.001), acute kidney injury (6.8% vs 1.1%, p = 0.006). As well, there was a significant increase in the number of patients receiving medical reviews following clinical deterioration in terms of escalation plan (3.2% vs 26.4%, p = <0.001).

Conclusion: The implementation of NEWS was associated with a significant improvement in patients' outcomes in hospital wards, increases in the frequency of vital signs measurements, and an increase in the number of medical reviews following clinical instability.
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http://dx.doi.org/10.2147/JMDH.S312395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214550PMC
June 2021

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study.

J Clin Med 2021 May 14;10(10). Epub 2021 May 14.

Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41-1.37), = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23-1.22), = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (-0.14 days (95% CI: -3.19-2.91 days), = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.
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http://dx.doi.org/10.3390/jcm10102113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153619PMC
May 2021

Novel 4-(piperazin-1-yl)quinolin-2(1H)-one bearing thiazoles with antiproliferative activity through VEGFR-2-TK inhibition.

Bioorg Med Chem 2021 06 22;40:116168. Epub 2021 Apr 22.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt; Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Minia, Egypt. Electronic address:

A new series of 2-(4-(2-oxo-1,2-dihydroquinolin-4-yl)piperazin-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives were synthesized and evaluated for anticancer activity. All target compounds showed anticancer activity higher than that of their 2-oxo-4-piperazinyl-1,2-dihydroquinolin-2(1H)-one precursors. Multidose testing of target compounds was performed against breast cancer T-47D cell line. Five compounds showed higher cytotoxic activity than Staurosporine. The dihalogenated derivative showed the best cytotoxic activity with IC 2.73 ± 0.16 µM. In addition, the VEGFR-2 inhibitory activity of all synthetic compounds was evaluated. Two compounds of 6-fluoro-4-(piperazin-1-yl)quinolin-2(1H)-ones showed inhibitory activity comparable to sorafenib with IC 46.83 ± 2.4, 51.09 ± 2.6 and 51.41 ± 2.3 nM, respectively. The cell cycle analysis of two compounds namely, 2-(4-(6-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)piperazin-1-yl)-N-(4-phenylthiazol-2-yl)acetamide and N-(4-(4-chlorophenyl)thiazol-2-yl)-2-(4-(2-oxo-1-phenyl-1,2-dihydroquinolin-4-yl)piperazin-1-yl)acetamide revealed that the arrest of cell cycle occurred at S phase. In apoptosis assay, the same two compounds were able to induce significant levels of early and late apoptosis. In a similar manner to Sorafenib, docking of target compounds with VEGFR-2 protein 4ASD showed HB with Cys919 in hinge region of enzyme and HB with both Glu885 and Asp1046 in gate area. Using SwissADME, all target compounds were predicted to be highly absorbed from gastrointestinal tract with no BBB permeability. It is clear that the two compounds are promising antiproliferative candidates that require further optimization.
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http://dx.doi.org/10.1016/j.bmc.2021.116168DOI Listing
June 2021

Severe Acute Kidney Injury in Critically Ill Patients with COVID-19 Admitted to ICU: Incidence, Risk Factors, and Outcomes.

J Clin Med 2021 Mar 15;10(6). Epub 2021 Mar 15.

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.

Background: Critically ill patients with COVID-19 are prone to develop severe acute kidney injury (AKI), defined as KDIGO (Kidney Disease Improving Global Outcomes) stages 2 or 3. However, data are limited in these patients. We aimed to report the incidence, risk factors, and prognostic impact of severe AKI in critically ill patients with COVID-19 admitted to the intensive care unit (ICU) for acute respiratory failure.

Methods: A retrospective monocenter study including adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection admitted to the ICU for acute respiratory failure. The primary outcome was to identify the incidence and risk factors associated with severe AKI (KDIGO stages 2 or 3).

Results: Overall, 110 COVID-19 patients were admitted. Among them, 77 (70%) required invasive mechanical ventilation (IMV), 66 (60%) received vasopressor support, and 9 (8.2%) needed extracorporeal membrane oxygenation (ECMO). Severe AKI occurred in 50 patients (45.4%). In multivariable logistic regression analysis, severe AKI was independently associated with age (odds ratio (OR) = 1.08 (95% CI (confidence interval): 1.03-1.14), = 0.003), IMV (OR = 33.44 (95% CI: 2.20-507.77), = 0.011), creatinine level on admission (OR = 1.04 (95% CI: 1.008-1.065), = 0.012), and ECMO (OR = 11.42 (95% CI: 1.95-66.70), = 0.007). Inflammatory (interleukin-6, C-reactive protein, and ferritin) or thrombotic (D-dimer and fibrinogen) markers were not associated with severe AKI after adjustment for potential confounders. Severe AKI was independently associated with hospital mortality (OR = 29.73 (95% CI: 4.10-215.77), = 0.001) and longer hospital length of stay (subhazard ratio = 0.26 (95% CI: 0.14-0.51), < 0.001). At the time of hospital discharge, 74.1% of patients with severe AKI who were discharged alive from the hospital recovered normal or baseline renal function.

Conclusion: Severe AKI was common in critically ill patients with COVID-19 and was not associated with inflammatory or thrombotic markers. Severe AKI was an independent risk factor of hospital mortality and hospital length of stay, and it should be rapidly recognized during SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/jcm10061217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998509PMC
March 2021

Draft Genome Sequences and Antimicrobial Profiles of Three Staphylococcus epidermidis Strains from Neonatal Blood Samples.

Microbiol Resour Announc 2021 Apr 1;10(13). Epub 2021 Apr 1.

Luebeck Institute for Experimental Dermatology, University of Luebeck, Luebeck, Germany.

Data on molecular characterization of coagulase-negative staphylococci causing neonatal sepsis in low-income countries are highly limited. This report highlights the isolation of three non-genome assembly strains (NGASs) from blood samples from neonates with unknown transmission sources. Pathogenic factors and sources of transmission of these strains warrant further investigation.
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http://dx.doi.org/10.1128/MRA.00170-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104051PMC
April 2021

Engineered biochars from catalytic microwave pyrolysis for reducing heavy metals phytotoxicity and increasing plant growth.

Chemosphere 2021 May 30;271:129808. Epub 2021 Jan 30.

Department of Aeronautics and Astronautics, National Cheng Kung University, Taiwan.

Pb, Ni, and Co are among the most toxic heavy metals that pose direct risks to humans and biota. There are no published studies on biochars produced at low temperatures (i.e., 300 °C), which possess high sorption capacity for heavy metal remediation and reclamation of contaminated sandy soils. This research studied the effect of catalytic microwave pyrolysis of switchgrass (SG) using bentonite and KPO to produce biochar at low temperature (300 °C) with high sorption capacity for reducing the phytotoxicity of heavy metals, and investigated the synergistic effects of catalyst mixture on biochar sorption capacity. The quality of the biochars was examined in terms of their impacts on plant growth, reducing phytotoxicity and uptake of heavy metals in sandy soil spiked with Pb, Ni, and Co. All catalysts increased the micropore surface area and cation-exchange capacity of biochars, and resulted in biochars rich in plant nutrients, which not only decreased heavy metal phytotoxicity, but also boosted plant growth in the spiked soil by up to 140% compared to the sample without biochar. By mixing bentonite and KPO with SG during microwave pyrolysis, the efficacy of biochar in reducing phytotoxicity and heavy metals uptake was further enhanced because of the highest micropore surface area (402 m/g), moderate contents of Ca, Mg, K, and Fe for ion-exchange and moderate concentration of phosphorus for the formation of insoluble heavy metal compounds. Generally, the biochar created at 300 °C (300-30KP) showed similar performance to the biochar created at 400 °C (400-30KP) in terms of reducing heavy metal bioavailability.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129808DOI Listing
May 2021

Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets for -Induced Gastric Disease.

Front Immunol 2021 24;12:624117. Epub 2021 Feb 24.

Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center-University of Freiburg, Freiburg, Germany.

is a gram-negative bacterium that colonizes the human gastric mucosa and can lead to gastric inflammation, ulcers, and stomach cancer. Due to the increase in antimicrobial resistance new methods to identify the molecular mechanisms of induced pathology are urgently needed. Here we utilized a computational biology approach, harnessing genome-wide association and gene expression studies to identify genes and pathways determining disease development. We mined gene expression data related to infection and its complications from publicly available databases to identify four human datasets as discovery datasets and used two different multi-cohort analysis pipelines to define a induced gene signature. An initial -signature was curated using the MetaIntegrator pipeline and validated in cell line model datasets. With this approach we identified cell line models that best match gene regulation in human pathology. A second analysis pipeline through NetworkAnalyst was used to refine our initial signature. This approach defined a 55-gene signature that is stably deregulated in disease conditions. The 55-gene signature was validated in datasets from human gastric adenocarcinomas and could separate tumor from normal tissue. As only a small number of patients develop cancer, this gene-signature must interact with other host and environmental factors to initiate tumorigenesis. We tested for possible interactions between our curated gene signature and host genomic background mutations and polymorphisms by integrating genome-wide association studies (GWAS) and known oncogenes. We analyzed public databases to identify genes harboring single nucleotide polymorphisms (SNPs) associated with gastric pathologies and driver genes in gastric cancers. Using this approach, we identified 37 genes from GWA studies and 61 oncogenes, which were used with our 55-gene signature to map gene-gene interaction networks. In conclusion, our analysis defines a unique gene signature driven by infection at early phases and that remains relevant through different stages of pathology up to gastric cancer, a stage where itself is rarely detectable. Furthermore, this signature elucidates many factors of host gene and pathway regulation in infection and can be used as a target for drug repurposing and testing of infection models suitability to investigate human infection.
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http://dx.doi.org/10.3389/fimmu.2021.624117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945594PMC
September 2021

Effects of Methylprednisolone on Ventilator-Free Days in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome and COVID-19: A Retrospective Study.

J Clin Med 2021 Feb 14;10(4). Epub 2021 Feb 14.

Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi 112412, United Arab Emirates.

There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone is associated with increases in the number of ventilator-free days (VFDs) among these patients. Retrospective single-center study. Intensive care unit. All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included. None. The primary outcome was ventilator-free days (VFDs) for the first 28 days. Defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray's proportional sub hazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg·kg (IQR: 1-1.3 mg·kg) and median duration for 5 days (IQR: 5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61, 95% CI, 1.10-8.12, = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95% CI: 0.02-0.45, = 0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, = 0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR: 15-41 days] vs. 37 days [IQR: 23-52 days], = 0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, = 0.052). However, 81% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.
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http://dx.doi.org/10.3390/jcm10040760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917584PMC
February 2021

Intracranial hemorrhage in primary immune thrombocytopenia (ITP): 20 years' experience in pediatrics.

Eur J Pediatr 2021 May 15;180(5):1545-1552. Epub 2021 Jan 15.

Department of Pediatric Hematology/Oncology, Alexandria University, Alexandria, Egypt.

Incidence of intracranial hemorrhage (ICH) among children with primary immune thrombocytopenia (ITP) varies among different studies. We published data during the period of 1997-2007 of ICH in children with primary ITP, addressing risk factors and outcome. The aim of this study is to assess changes in incidence, risk factors, and outcome of ICH in children with ITP from last decade and to report the overall 20 years' experience. We compared 2008-2018 with the decade before it. Data of children with ITP and ICH during study period and ITP control cases were analyzed. Neurosurgical intervention and outcome were also reported. A total of 4340 children with primary ITP were evaluated. Twenty-five (0.63%) ICH events were reported over 2 decades. Head trauma, hematuria, and platelet counts < 10 × 109/L were the risk factors mostly associated with ICH. Overall mortality was 24%, and a further 28% had neurologic sequelae. Neurosurgical intervention was done in 12% of cases with good outcome.Conclusion: Persistent platelet counts < 10 × 109/L were a significant risk factor for ICH in both time periods, while head trauma and hematuria were more reported in the period of 2008-2018 as significant risk factors for ICH. Outcome was comparable in both periods. What is Known: • ICH is a rare complication of ITP; however, early recognition of risk factors and aggressive treatment might lead to complete recovery without sequalae. Platelet counts less than < 10 × 109/L are the main risk factor for ICH. Few studies reported other significant risk factors. What is New: • Hematuria and head trauma are significant risk factors for ICH in ITP, in addition to having a persistently low platelet count < 10 × 109/L. (more than 90 days in chronic ITP, 45 days in persistent and 21 days in acute ITP) • Combined treatment with IVIG and HDMP followed by platelet transfusion was associated with complete recovery without sequelae in almost 50% of patients.
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http://dx.doi.org/10.1007/s00431-020-03923-xDOI Listing
May 2021

Synthesis, antitumor, antibacterial and urease inhibitory evaluation of new piperazinyl N-4 carbamoyl functionalized ciprofloxacin derivatives.

Pharmacol Rep 2021 Jun 3;73(3):891-906. Epub 2021 Jan 3.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.

Background: Quinolones are well known antibacterial chemotherapeutics. Furthermore, they were reported for other activities such as anticancer and urease inhibitory potential. Modification at C7 of quinolones can direct these compounds preferentially toward target molecules.

Methods: Different derivatives of ciprofloxacin by functionalization at the piperazinyl N-4 position with arylidenehydrazinecarbonyl and saturated heterocyclic-carbonyl moieties have been synthesized and characterized using different spectral and analytical techniques. The synthesized compounds were evaluated for anticancer, antibacterial, and urease inhibitory activities.

Results: Among the synthesized compounds derivatives 3f and 3g experienced a potent antiproliferative activity against the breast cancer BT-549 cell line, recording growth percentages of 28.68% and 6.18%, respectively. Additionally, compound 3g revealed a remarkable antitumor potential toward the colon cancer HCT-116 cells (growth percentage 14.76%). Activity of compounds 3f and 3g against BT-549 cells was comparable to doxorubicin (IC = 1.84, 9.83, and 1.29 µM, respectively). Test compounds were less active than their parent drug, ciprofloxacin toward Klebsiella pneumoniae and Proteus mirabilis. However, derivative 4a showed activity better than chloramphenicol against Klebsiella pneumoniae (MIC = 100.64 and 217.08 µM, respectively). Meanwhile, many of the synthesized compounds revealed a urease inhibitory activity greater than their parent. Compound 3i was the most potent urease inhibitor with IC of 58.92 µM, greater than ciprofloxacin and standard inhibitor, thiourea (IC = 94.32 and 78.89 µM, respectively).

Conclusion: This study provided promising derivatives as lead compounds for development of anticancer agents against breast and colon cancers, and others for optimization of urease inhibitors.
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http://dx.doi.org/10.1007/s43440-020-00193-0DOI Listing
June 2021

Synergistic Effects of Catalyst Mixtures on Biomass Catalytic Pyrolysis.

Front Bioeng Biotechnol 2020 14;8:615134. Epub 2020 Dec 14.

Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, Canada.

This paper studied the synergistic effects of catalyst mixtures on biomass catalytic pyrolysis in comparison with the single catalyst in a microwave reactor and a TGA. In general, positive synergistic effects were identified based on increased mass loss rate, reduced activation energy, and improved bio-oil quality compared to the case with a single catalyst at higher catalyst loads. 10KP/10Bento (a mixture of 10% KPO and 10% bentonite) increased the mass loss rate by 85 and 45% at heating rates of 100 and 25°C/min, respectively, compared to switchgrass without catalyst. The activation energy for 10KP/10Bento and 10KP/10Clino (a mixture of 10% KPO and 10% clinoptilolite) was slightly lower or similar to other catalysts at 30 wt.% load. The reduction in the activation energy by the catalyst mixture was higher at 100°C/min than 25°C/min due to the improved catalytic activity at higher heating rates. Synergistic effects are also reflected in the improved properties of bio-oil, as acids, aldehydes, and anhydrosugars were significantly decreased, whereas phenol and aromatic compounds were substantially increased. 30KP (30% KPO) and 10KP/10Bento increased the content of alkylated phenols by 341 and 207%, respectively, in comparison with switchgrass without catalyst. Finally, the use of catalyst mixtures improved the catalytic performance markedly, which shows the potential to reduce the production cost of bio-oil and biochar from microwave catalytic pyrolysis.
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http://dx.doi.org/10.3389/fbioe.2020.615134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767908PMC
December 2020

Clinical features and laboratory characteristics of patients hospitalized with COVID-19: single centre report from Egypt.

J Infect Dev Ctries 2020 12 31;14(12):1352-1360. Epub 2020 Dec 31.

Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.

Introduction: The recently discovered novel coronavirus disease (COVID-19) has emerged in Wuhan, China, since January 2020. Egypt reported a low incidence of infection when compared with other countries. The aim of the study was to assess the characterization of COVID-19 infection among the Egyptian population.

Methodology: Data were collected from a single COVID-19 quarantine hospital in Cairo. A total number of 195 cases were included with their clinical, laboratory, and radiological data.

Results: Three different age groups behaved differently for COVD-19 infection. The pediatric age group was asymptomatic entirely, the middle age group (18-50 years) were asymptomatic in 53.3% of cases, while 77.9% of those above 50 years were symptomatic (p ≤ 0.001). The latter group had a high incidence of COVID-pneumonia in (83.1%), and moderate to critical presentations were encountered in 66.3% of them. Neutrophil to lymphocyte (N/L) ratio correlated directly with the age and case severity. C-reactive protein (CRP) and computed tomography scan chest (CT-chest) had added value on COVID-19 diagnosis in suspected cases.

Conclusions: In Egypt, patients above 50 years are at a higher risk for symptomatic COVID-19 infection and leaner for moderate to critical COVID-19 presentation. The triad of CT-chest, CRP, and N/L ratio could be an integrated panel for assessing disease severity.
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http://dx.doi.org/10.3855/jidc.13156DOI Listing
December 2020

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

Br J Clin Pharmacol 2021 08 19;87(8):3075-3091. Epub 2021 Jan 19.

Sackler Institute of Pulmonary Pharmacology, King's College London, UK.

Aims: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis.

Methods: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes.

Analysis: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn.

Trial Registration, Ethics And Dissemination: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.
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http://dx.doi.org/10.1111/bcp.14714DOI Listing
August 2021

Antimicrobial Susceptibility Patterns and Wild-Type MIC Distributions of Anaerobic Bacteria at a German University Hospital: A Five-Year Retrospective Study (2015-2019).

Antibiotics (Basel) 2020 Nov 18;9(11). Epub 2020 Nov 18.

Institute of Medical Microbiology and Hygiene, Medical Center, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Local antimicrobial susceptibility surveys are crucial for optimal empirical therapy guidelines and for aiding in antibiotic stewardship and treatment decisions. For many laboratories, a comprehensive overview of local antimicrobial susceptibility patterns of anaerobic bacteria is still lacking due to the long incubation time and effort involved. The present study investigates the antimicrobial susceptibility patterns and related clinical and demographic data of 2856 clinical isolates of anaerobic bacteria that were submitted for analysis to the Institute for Medical Microbiology and Hygiene of the Freiburg University Medical Center (a tertiary university medical center in Southern Germany) between 2015 and 2019. Antimicrobial susceptibility testing has been carried out according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. Minimum inhibitory concentration (MIC) and MIC for penicillin, metronidazole, moxifloxacin, and clindamycin were established for Gram-positive anaerobes and for ampicillin-sulbactam, meropenem, metronidazole, moxifloxacin, and clindamycin for Gram-negative anaerobes. The distribution of MIC-values for various antibiotics against anaerobic bacteria was also established, especially for those having no specific breakpoints according to EUCAST guidelines. Most clinically relevant anaerobic bacteria originated from general surgery, neurological, and orthopedic wards. A high proportion of isolates were resistant to moxifloxacin and clindamycin indicating the importance of their susceptibility testing before administration. Based on our study metronidazole and other β-lactam/β-lactamase inhibitor combinations such as ampicillin-sulbactam remain suitable for empirical treatment of infections with anaerobic bacteria.
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http://dx.doi.org/10.3390/antibiotics9110823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698766PMC
November 2020

Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors.

Eur J Med Chem 2021 Jan 8;209:112904. Epub 2020 Oct 8.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Minia, Egypt. Electronic address:

Despite the encouraging clinical progress of chemotherapeutic agents in cancer treatment, innovation and development of new effective anticancer candidates still represents a challenging endeavor. With 15 million death every year in 2030 according to the estimates, cancer has increased rising of an alarm as a real crisis for public health and health systems worldwide. Therefore, scientist began to introduce innovative solutions to control the cancer global health problem. One of the promising strategies in this issue is the multitarget or smart hybrids having two or more pharmacophores targeting cancer. These rationalized hybrid molecules have gained great interests in cancer treatment as they are capable to simultaneously inhibit more than cancer pathway or target without drug-drug interactions and with less side effects. A prime important example of these hybrids, the HDAC hybrid inhibitors or referred as multitargeting HDAC inhibitors. The ability of HDAC inhibitors to synergistically improve the efficacy of other anti-cancer drugs and moreover, the ease of HDAC inhibitors cap group modification prompt many medicinal chemists to innovate and develop new generation of HDAC hybrid inhibitors. Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. This review shed light on the most recent hybrids of HDACIs with one or more other cancer target pharmacophore. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This review may help researchers in development and discovery of new horizons in cancer treatment.
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http://dx.doi.org/10.1016/j.ejmech.2020.112904DOI Listing
January 2021

Physical activity and its associated factors in females with type 2 diabetes in Riyadh, Saudi Arabia.

PLoS One 2020 1;15(10):e0239905. Epub 2020 Oct 1.

Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

Despite the benefits of physical activity (PA) for the management of type 2 diabetes Mellitus (T2DM), the topic of PA is poorly addressed in Saudi Arabia (SA), especially in females with T2DM. The present study examined PA and its associated factors in females with T2DM in Riyadh, Saudi Arabia. This observational cross-sectional study was performed in a random sample of 372 women with T2DM. A face-to-face interview that covered PA, health and environmental correlates of PA was performed. Discriminant analysis was used to determine which barriers had the greatest impact on PA in these women. The results showed that approximately 26.3% of the study participants met PA recommendations. Multivariate linear regression revealed lower levels of PA were associated with women who had more than three children (β = -0.17) compared to women with no children, older age (β = -0.18), women with a duration of diabetes ≥ 6 years (β = -0.16), women who were obese (β = -0.23), women with no family support (β = -0.20), no friend support (β = -0.13) and no healthcare provider support (β = -0.14). Discriminant analysis indicated that culture and tradition, lack of skills and knowledge, safety, fatigue, lack of time, weather conditions, and lack of facilities were the barriers that differentiated between the women who met and those who did not meet the PA recommendations. The present study suggests that the prevalence of PA is low and number of children, age, duration of diabetes, Obesity, family support, friend support and healthcare provider support are identified correlates of PA. These findings are valuable and should be used to design and implement future PA interventions, especially for women with T2DM. Healthcare providers may improve exercise levels and identify the specific barriers to reaching the recommended level of PA to improve health outcomes for each patient.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529343PMC
November 2020

Evaluation of the effect of some medicinal plants on cultured Trichomonas Vaginalis.

J Infect Dev Ctries 2020 07 31;14(7):793-799. Epub 2020 Jul 31.

Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: Trichomoniasis is a worldwide sexually transmitted disease caused by Trichomonas vaginalis. It inflicts severe complications to the human genitourinary system. The devastating negative effects and the emergence of resistance to common medication impose the search for safer and effective alternatives. This research aimed to investigate the effect of the Allium sativum, Nigella sativa crude extracts (NsCE) and the combination between their most effective doses with metronidazole.

Methodology: Vaginal swabs were obtained from symptomatic patients, and cultured on Diamond's medium. Assessment of various concentrations of these herbs at different follow-up periods was done by counting the number of dead T. vaginalis trophozoites using the hemocytometer and trypan blue staining. Transmission electron microscope study was done.

Results: NsCE 9 mg/mL yielded the highest lethal effect on T. vaginalis trophozoites after 72 hours, compared with metronidazole. Combination of NsCE 9 mg/mL and metronidazole 50 µg/mL gave the best result. Additionally, Tomex90 µg/mL, represents a tolerable effect after 72 hours, but metronidazole 100 µg/mL still has higher effect. These results were confirmed by the ultrastructural changes observed in T. vaginalis trophozoites, signifying severe damage of nucleus and cytoplasm with large vacuolization and cell membrane defects.

Conclusions: NsCE is a promising anti-Trichomonas especially its combination with metronidazole which showed a high synergistic effect.
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http://dx.doi.org/10.3855/jidc.11580DOI Listing
July 2020

Deciphering pyrethroid resistance in Cx. pipiens (L): Implications of cytochrome P450; expression profiling and regulatory microRNA.

Mol Cell Probes 2020 08 28;52:101579. Epub 2020 Apr 28.

Faculty of Science, Cairo University, Giza, Egypt; Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt. Electronic address:

Over the past decades, the extensive use of pyrethroids insecticides for vector control has resulted in the development of insecticide resistance. Cytochrome P450 has been recognized to play a critical role in the metabolic detoxification of insecticides. In the current study, Culex pipiens mosquitoes were collected from Giza Governorate in Egypt and tested for insecticide susceptibility against deltamethrin. First detection of Knockdown resistance gene (Kdr) mutations in field collected mosquitoes was performed. Activities of cytochrome oxidase P450 detoxification enzyme that synchronized with the resistance development, was assessed. Expression profiles of cytochrome P450s and their putative corresponding regulating miRNAs, which was previously reported in Cx. pipiens pallens were evaluated in pyrethroid resistant field-collected Cx. pipiens using RT-qPCR and stem-loop RT-qPCR, respectively. Specific stem-loop reverse transcription primers and forward primers were designed for miRNAs profiling. Our results elucidated the pyrethroid resistance development and revealed its relation to the metabolic and target site modification mechanisms with a first report of L1014F-kdr mutation detection. RT-qPCR results have showed an up-regulation in the expression of the studied P450 transcripts. Negative correlations were found between the expression of P450s and their regulatory miRNAs except for CYP9J35, where positive correlation was found with its corresponding miR-13. Interestingly, our data was the first to detect negative correlation between miR-285 and its putative CYP6Cp1 target gene. These findings highlighted the significance of identifying P450 gene along with regulatory miRNAs as a key mechanism implicated in pyrethroid resistance in field Culex vector population. The elucidation of this mechanism would shed light on the development of insecticide resistance and would help in shaping strategies to combat such vectors.
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http://dx.doi.org/10.1016/j.mcp.2020.101579DOI Listing
August 2020

Food Selection Under Stress Among Undergraduate Students in Riyadh, Saudi Arabia.

Psychol Res Behav Manag 2020 28;13:211-221. Epub 2020 Feb 28.

Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.

Background: University students might experience numerous sources of stress in their daily lives. Previous research has found that stress affects food selection patterns, but the effect might vary by country and sex. No previous study conducted in Saudi Arabia has assessed the association between stress and dietary habits among university students. Thus, this study aimed to examine the association between perceived stress and food selection patterns among undergraduate students by sex at King Saud University (KSU).

Methods: A cross-sectional study of 400 students attending the College of Applied Medical Sciences in Riyadh, Saudi Arabia, was conducted. The self-administered questionnaire that was used consisted of three sections: sociodemographic, food frequency questionnaire, and Cohen's Perceived Stress Scale.

Results: Approximately (59.0%) of the participants reported suffering from some level of stress, with more females (64.5%) experiencing stress than males (54.0%). The univariate analysis showed that under stress, more females (68.0%) reported eating more than usual than males (49.0%), while the percentage of respondents that reported eating less than usual was higher for females (23.0%) than that for males (31.0%). The McNemar test indicated that under stress, there was an increased preference for salty flavors, which was not associated with sex. Significantly more females (82.0%) than males (64.5%) reported preferring sweets under stress. More males reported preferring bitter and savory flavors than females. Under stress, females preferred homemade food, while males preferred takeout foods. More females (68.0%) reported losing control and overeating than males (49.0%). A logistic regression showed that for female students, perceived stress was associated with frequent consumption of sweets, cake/cookies, snacks and beverages and less frequent consumption of fruits and vegetables. For males, the consumption of fast food and meat was significantly positively associated with perceived stress.

Conclusion: Perceived stress led to unhealthy changes in eating patterns in both sexes, as evidenced by reports of an increased preference for sweets, snacks and cake/cookies among females and an increased preference for fast food and meat among males. These results may be potentially important targets for interventions for stress-related food consumption.
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http://dx.doi.org/10.2147/PRBM.S236953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053809PMC
February 2020

Malnutrition is common in children with cerebral palsy in Saudi Arabia - a cross-sectional clinical observational study.

BMC Neurol 2019 Dec 10;19(1):317. Epub 2019 Dec 10.

Clinical Nutrition Program, Department of Community Health Sciences, College of Applied Medical sciences. King Saud University, Riyadh, Saudi Arabia.

Background: Cerebral palsy (CP) is considered as the main cause of severe physical impairment and malnutrition in children. This cross-sectional study intended to survey the nutritional status of children cerebral palsy in Riyadh, Saudi Arabia.

Methods: We examined 74 children (age: 1-10 yrs) with CP, who attended Sultan Bin Abdulaziz Humanitarian City (SBAHC), Riyadh Saudi Arabia. Data on age, general demographics, nutritional status, and dietary intake were collected. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for his/her weight for age, weight for height, height for age and body mass index for age were ≤ -2.0 standard deviation (SD) using WHO growth standards. Multivariable logistic regression identified the factors associated with nutritional indicators.

Results: More than half (56.4%) of the children with cerebral palsy were malnourished as they had z-score below <-2 SD in at least one of the four indicators. Thinness (50%) was the most common form of malnutrition, followed by underweight, stunting, and wasting. Arm anthropometrics gave similar results on the percent number of malnourished children. Factors that were independently associated with malnutrition with an adjusted OR (aOR) were as follow: age ≤ 5 yrs. (aOR: 4.29); presence of cognitive impairment (aOR: 4.13); presence of anemia (aOR: 3.41) and inadequate energy intake (aOR: 4.86) (p, for all trends <0.05).

Conclusion: Children with cerebral palsy of the current study have impaired growth and nutritional status as assessed by all four common nutritional status indicators. Further large-scale community-based studies for in-depth evaluation of nutritional status and growth patterns in children with CP are needed.
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http://dx.doi.org/10.1186/s12883-019-1553-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905047PMC
December 2019

Morphomolecular analysis of the immune tumor microenvironment in human head and neck cancer.

Cancer Immunol Immunother 2019 Sep 23;68(9):1443-1454. Epub 2019 Aug 23.

Institute of Pathology, Charité Hospital, Berlin, Germany.

Immunotherapy is effective in head and neck squamous cell carcinoma (HNSCC), but only a minority of patients responds to immune checkpoint blockade (ICB). To contribute to a better understanding of the underlying immune biology, we combined histomorphological evaluation and molecular analysis of the HNSCC immune microenvironment in the TCGA cohort. Analyzing digital HE-stained slides, a method for classification of tumor infiltrating lymphocytes (TILs) in the intra-epithelial compartment (ieTILs, present vs. absent) and the stromal compartment (strTILs, high vs. low) was established. We also analyzed the abundance of eight immune cell populations (estimated from RNAseq data) and PD-L1 mRNA expression. Status of ieTILs and status of strTILs were concordant for 61%, but discordant for 39% of tumors. In univariate survival analysis, ieTILs were a positive prognostic marker for DFS in the study cohort (HR = 0.66, p = 0.015) and in the HPV- subcohort (HR = 0.68, p = 0.04), but not in the HPV + subcohort. T cells were a positive prognostic marker for DFS in the study cohort (HR = 0.80, p = 0.03) and in the HPV + subcohort (HR = 0.20, p = 0.001), but not in the HPV- subcohort. In univariate survival analysis, PD-L1 mRNA expression was neither associated with DFS nor with OS. However, in bivariate and multivariate analyses including both PD-L1 mRNA levels and T cells, PD-L1 was a negative prognostic marker of DFS and OS, while T cells remained a positive prognostic marker. In conclusion, ieTILs and strTILs were non-redundant biomarkers in HNSCC and should be evaluated separately. The identified prognostic markers should be evaluated for predictivity in ICB-treated patients.
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http://dx.doi.org/10.1007/s00262-019-02378-wDOI Listing
September 2019

Paulownia Leaves as A New Feed Resource: Chemical Composition and Effects on Growth, Carcasses, Digestibility, Blood Biochemistry, and Intestinal Bacterial Populations of Growing Rabbits.

Animals (Basel) 2019 Mar 18;9(3). Epub 2019 Mar 18.

Department of Animal Production, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.

This experiment was conducted to study the effects of paulownia leaf meal (PLM) as a nontraditional feed on the growth, carcasses, digestibility, blood chemistry, and intestinal microbiota of growing rabbits. Sixty rabbits (5-weeks old) were randomly allotted to three dietary treatments containing three amounts of PLM (0%, 15%, and 30%). The results showed that PLM has a higher content of ether extract, organic matter, methionine, tyrosine, histidine, manganese, and zinc than alfalfa hay. Body weight gain decreased when 30% PLM was provided. The best feed conversion ratio was recorded in the rabbits fed 15% PLM. A notable increase in high-density lipoprotein levels with a significant decrease in low-density lipoprotein was noted in the rabbits fed the PLM diets. Total fungi and Enterobacteriaceae and total bacterial count in the feed were significantly reduced because of PLM. In the cecum, coliforms, Enterobacteriaceae species, and total bacterial count declined in the rabbits fed the PLM diets. Conclusively, up to 15% PLM can be used in rabbit diets without any deleterious effects on the performance, nutrient digestibility, and blood constituents. In addition, dietary inclusion of PLM has the potential to reduce cecal pathogenic bacteria in rabbits.
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http://dx.doi.org/10.3390/ani9030095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466076PMC
March 2019

The clinical impact of miRNA34a and P53 gene expression in colon cancer.

Biochem Biophys Rep 2018 Dec 24;16:88-95. Epub 2018 Oct 24.

Department of Organic chemistry, Faculty of science - Menoufia University, Egypt.

Objective: To study the potential role of miRNA34a gene expression and its relationship with P53 gene expression, fate, stage, metastasis and overall survival of colorectal cancer.

Patients And Methods: This study was carried out 30 patients with colon adenocarcinoma, 30 patients with benign colon polyp and 30 apparently healthy persons served as controls. All participants were subjected to full history taking, general clinical examination. Complete blood count, liver and kidney function, determination of serum tumor markers were done. Estimation of microRNA 34a and P53 Gene expression by real-time PCR were done.

Results: There was a significant negative relationship between serum tumor markers and micro RNA 34a gene expression in cancer patients. Also, there was a statistically significant positive relationship between miRNA34a gene expression and P53 gene expression in both patients groups. The diagnostic accuracy of miRNA34a gene expression was both sensitive and specific for colon cancer. MiRNA34a and P53 gene expression had statistically significant relation with tumor stage and presence of metastases.

Conclusion: It can be concluded that the level of miRNA34a can be used to differentiate between colon cancers and begin adenomas. MiRNA34a can be used as a prognostic marker in colon cancer.
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http://dx.doi.org/10.1016/j.bbrep.2018.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202666PMC
December 2018

Performance of 2 Polymerization Protocols Targeting Cloned Toxoplasma Parasites.

Open Access Maced J Med Sci 2018 Sep 22;6(9):1577-1580. Epub 2018 Sep 22.

Department of Molecular Diagnostics, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.

Background: is a common parasitic infection of humans. Infection is usually mild. Serious complications can occur in pregnant and immunocompromised patients.

Aim: The present study aims to investigate the performance of 2 different PCR protocols; real-time quantitative molecular assays (qPCR) and conventional molecular assays (cPCR), using 2 different sets of primers and by using cloned purified Toxoplasma genomic substances to be evaluated as reference samples.

Methods: The target DNA was provided in 8 different quantities.

Results: Amplification failure was reported only with the cPCR in samples of low concentrations using both primer sets. Quantitative PCR detected the 8 different dilutions of the purified using the 2 sets of primers while cPCR was sensitive to detect only 6 different dilutions.

Conclusion: Generally real-time quantitative molecular assays, is easy to use method compared to conventional PCR assay and produces more reliable results within only one hour time but still the possible application of qPCRs in routine diagnosis necessitates analysis of a large number of clinical samples in further studies to make the proper choice.
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http://dx.doi.org/10.3889/oamjms.2018.400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182548PMC
September 2018

Isothermal PCR for Feasible Molecular Diagnosis of Primary Toxoplasmosis in Women Recently Experienced Spontaneous Abortion.

Open Access Maced J Med Sci 2018 Jun 10;6(6):982-987. Epub 2018 Jun 10.

Department of Molecular Diagnostics, Genetic Engineering and Biotechnology Research Institute, City University, Cairo, Egypt.

Aim: The current study aimed to assess the practicability of a simple loop-mediated isothermal amplification (LAMP) about real-time quantitative PCR to diagnose primary toxoplasmosis among high-risk pregnant women.

Methods: Cloned Toxoplasma samples were used to calculate the analytical sensitivity while specificity was assessed using pooled DNA samples extracted from other parasitic stages.

Results: Both techniques showed 100% sensitivity and specificity and then applied to detect recent Toxoplasma infection in peripheral blood of 77 IgG negative women out of a total 139 women lately experienced spontaneous abortion. The 2 techniques obtained positive results in 8 samples confirming primary toxoplasmosis.

Conclusion: Generally, LAMP assay is a simple, cost-effective molecular technique can be completed in less than half an hour to diagnose primary Toxoplasma infection. The technique can be applied in a minimally equipped laboratory by ordinary workers to screen the vulnerable groups. Further analysis using larger samples with the quantitative approach is recommended to confirm the sensitivity of this emergent molecular technique.
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http://dx.doi.org/10.3889/oamjms.2018.227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026412PMC
June 2018

MBL2 gene polymorphism rs1800450 and rheumatic fever with and without rheumatic heart disease: an Egyptian pilot study.

Pediatr Rheumatol Online J 2018 Apr 13;16(1):24. Epub 2018 Apr 13.

Biochemistry Department-Faculty of Pharmacy (Boys), Al-Azhar University, Almokhayam Aldaem Street, 6th Province - 13465 Nasr City, Cairo, Egypt.

Background: Rheumatic fever (RF) is the result of an autoimmune response to pharyngitis caused by infection with Streptococcus pyogenes. RF is most prevalent in Africa and the Middle East. Rheumatic heart disease (RHD) is the most serious complication of RF. Mannose-binding lectin 2 gene (MBL2) has been reported to be correlated with different cardiac conditions. In Egyptian patients as a new studied ethnic population, it is the first time to evaluate the association between MBL2 gene polymorphism rs1800450 and RF with and without RHD.

Methods: One hundred and sixty RF patients (80 with RHD and 80 without RHD) and eighty healthy ethnically matched controls were studied. MBL2 (rs1800450) was genotyped by real-time PCR using TaqMan® allele discrimination assay. The MBL level was measured by ELISA. Westergren erythrocytes sedimentation rate (ESR), anti-streptolysin O titer (ASOT), C-reactive protein (CRP) and complements (C3 and C4) were determined.

Results: The AA genotype with high production of MBL was associated with increased risk of RHD more than the B allele carrying subjects. However, MBL2 genotype related to the low production of MBL was more frequently observed in those patients without RHD.

Conclusions: Our results suggested the involvement of MBL2 (rs1800450) polymorphism and its protein in RHD pathogenesis. Also, it might be a promising future strategy to utilize this polymorphism to help differentiate patients with RHD from those without RHD.
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http://dx.doi.org/10.1186/s12969-018-0245-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899397PMC
April 2018

An overview of Jatropha curcas meal-induced productive and reproductive toxicity in Japanese quail: Potential mechanisms and heat detoxification.

Theriogenology 2018 Jun 12;113:208-220. Epub 2018 Mar 12.

Poultry Department, Agriculture Faculty, Zagazig University, Zagazig 44511, Egypt.

The present study was carried out to investigate the toxic effects of dietary inclusion of raw Jatropha cucas meal [RJM, 3.5%] on productive and reproductive performances of laying Japanese quail and the influence of physical treatment of jatropha meal by heating at [100 c] for 24 or 48 h [JH or JH respectively] on reducing these effects. The inclusion of RJM in quail diets significantly decreased the egg production, fertility and hatchability percentages and resulted in a high mortality rate. While heat-treated jatropha meal [JH or JH] improved such undesirable effects. The levels of hepatic proteins related to lipid synthesis, cholesterol metabolism and those related to lipid synthesis and transporting to egg yolk were increased in JH and JH groups than RJM group. Hepatic contents of vitellogenin [VGT-II] and estrogen receptor α [ERα] and circulating estradiol [E2] were improved in JH than RJM and JH groups however still under the control values. On the other hand, estrogen receptor β [ERβ] were restored to normal control value in both JH and JH groups. Histopathological investigation revealed that RJM produced various alterations in the histoarchitecture of liver, ovary and oviducts but these alterations were reduced in both JH and JH groups. From the obtained data we concluded that heating of jatropha meal for 24 h improved its nutritive value and increasing the time of heating is preferable for reduction of the most of toxic impacts indicating that heat treatment can convert toxic jatropha meal to an alternative protein source for livestock feed in a cheap and clean way without combining any other types of treatments.
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http://dx.doi.org/10.1016/j.theriogenology.2018.03.011DOI Listing
June 2018
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