Publications by authors named "M Waleed Gaber"

177 Publications

Fatal temozolomide induced aplastic anemia in a female with Glioblastoma multiforme : A case report and literature review.

Clin Case Rep 2021 Mar 28;9(3):1641-1646. Epub 2021 Jan 28.

Department of Oncology National Center for Cancer Care & Research Hamad Medical Corporation Doha Qatar.

When seeing patients on Temozolomide with pancytopenia, aplastic anemia secondary to the drug should be considered early in the differentials to avoid permanent hematological suppression.
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http://dx.doi.org/10.1002/ccr3.3860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981661PMC
March 2021

Co-delivery of norfloxacin and tenoxicam in Ag-TiO/poly(lactic acid) nanohybrid.

Int J Biol Macromol 2021 Mar 8;180:771-781. Epub 2021 Mar 8.

Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt. Electronic address:

A nanohybrid formulation of silver‑titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO consists of a cubic phase of Ag with two phases of TiO (anatase and brookite). Ag nanoparticle fine spots coated with TiO were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.033DOI Listing
March 2021

Smart wearable devices in cardiovascular care: where we are and how to move forward.

Nat Rev Cardiol 2021 Mar 4. Epub 2021 Mar 4.

Department of Medical Education, Weill Cornell Medicine, Doha, Qatar.

Technological innovations reach deeply into our daily lives and an emerging trend supports the use of commercial smart wearable devices to manage health. In the era of remote, decentralized and increasingly personalized patient care, catalysed by the COVID-19 pandemic, the cardiovascular community must familiarize itself with the wearable technologies on the market and their wide range of clinical applications. In this Review, we highlight the basic engineering principles of common wearable sensors and where they can be error-prone. We also examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure. To date, challenges such as device accuracy, clinical validity, a lack of standardized regulatory policies and concerns for patient privacy are still hindering the widespread adoption of smart wearable technologies in clinical practice. We present several recommendations to navigate these challenges and propose a simple and practical 'ABCD' guide for clinicians, personalized to their specific practice needs, to accelerate the integration of these devices into the clinical workflow for optimal patient care.
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http://dx.doi.org/10.1038/s41569-021-00522-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931503PMC
March 2021

Microwave pre-treatment of canola seeds and flaked seeds for increased hot expeller oil yield.

J Food Sci Technol 2021 Jan 26;58(1):323-332. Epub 2020 May 26.

CSIRO Agriculture and Food, Melbourne, VIC Australia.

Microwave (MW) pre-treatment of canola seeds or flaked seeds was found to be a superior alternative to the conventional thermal pre-treatment (steam). Flaked seeds were "cooked" (heat-treated) with steam or using microwave treatments in the temperature range of 62-130 °C prior to expeller pressing. Microwave cooking at 100 °C resulted in the highest increase in the pressed oil yield, which is an increase of 3.7% (w/w) on a pressed oil basis or 9.0% (oil in seed basis) compared with steam cooking. Whole canola seeds conditioning was conducted with microwaves or steam, in the temperature range of 40-75 °C, followed by microwave or steam cooking at 100 °C to evaluate the effect of MW treatment during conditioning on the expeller oil yield. The use of a continuous microwave process for combined conditioning of whole seeds at 55 °C and subsequent cooking of flaked seeds at 100 °C resulted in a 4.0% increase in expeller oil yield, compared with steam conditioning and cooking. The influence of dry basis (db %) moisture contents of 5%, 11.5%, and 16.5% on oil yield after steam or MW treatments of seeds and flaked seeds was also studied. The moisture content of 11.5% (db %) yielded the highest net oil yield for both MW and steam at best conditioning and cooking temperatures of 55 °C and 100 °C, respectively. No significant impact of MW cooking was seen on oil quality compared with conventional steam cooking.
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http://dx.doi.org/10.1007/s13197-020-04545-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813898PMC
January 2021

NF-κB Blockade by NEMO Binding Domain Peptide Ameliorates Inflammation and Neurobehavioral Sequelae After Cranial Radiation Therapy in Juvenile Mice.

Int J Radiat Oncol Biol Phys 2021 Apr 9;109(5):1508-1520. Epub 2020 Dec 9.

Dept. of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas. Electronic address:

Purpose: Cranial radiation therapy (CRT) is a common treatment for pediatric brain tumor patients. However, side effects include significant neurobehavioral dysfunction in survivors. This dysfunction may in part be caused by inflammation, including increased production of tumor necrosis factor alpha (TNFα) and its receptor TNFR1, which can activate the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB). The TNFα blockade abrogates this inflammatory response, although it presents immunologic risks. Thus, modulation of pathway subsets may be preferable. Here, we test whether inhibition of NF-κB activation using an NF-κB essential modulator binding domain (NBD) peptide mitigates CRT-induced neuroinflammation and improves behavioral outcomes.

Methods And Materials: Male C57BL/6J 28-day old mice were randomized to saline (sham), 5 Gy whole-brain CRT, or CRT + NBD-peptide. Brain tissue was collected after 4 hours or 3 months for Western blot or immunohistochemistry. The cortex, corpus callosum (CC), and dentate gyrus were variably imaged for NF-κB-p65, IκBα, proliferation, apoptosis, necroptosis, TNFα, TNFR1, IBA-1, doublecortin, CD11c, and GFAP. Neurobehavioral changes were assessed by open field and elevated plus maze tests 3 months post-CRT.

Results: NF-κB expression increased in whole and nuclear fractions 4 hours after CRT and was abrogated by NBD treatment. Cell death increased and proliferation decreased after CRT, including within neuronal progenitors, with some loss mitigated by NBD. Increased levels of TNFα, IBA-1, and GFAP were found in the CC and cortex months after CRT and were limited by NBD. The anti-NF-κB peptide also improved neurobehavioral assessments, yielding improvements in anxiety and exploration.

Conclusions: Results suggest a role for NF-κB modulation by NBD peptide in the reduction of neuroinflammation and mitigation of behavioral complications after pediatric radiation therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.067DOI Listing
April 2021

A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction.

Proc Natl Acad Sci U S A 2020 12 23;117(49):31353-31364. Epub 2020 Nov 23.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion of Tsc22d3-expressing macrophages-all of which may limit inflammatory damage. SRC stimulation with MCB-613 (and derivatives) is a potential therapeutic approach for inhibiting cardiac dysfunction after MI.
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http://dx.doi.org/10.1073/pnas.2011614117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733826PMC
December 2020

Anti-Toxoplasma IgG Level in Type 2 Diabetic Patients: Does It Affect Glycemic Control?

Egypt J Immunol 2020 Jan;27(1):119-127

Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.

Toxoplasma gondii (T. gondii) is an important opportunistic parasite which can leads to severe complications, even death in immuno-deficient patients. Diabetes is a systemic disease; considers an important factor that increases susceptibility and risk of various infections in the host by affecting the host's immune system. The aim of the current study was to determine possible relations between toxoplasma IgG antibodies titer and the level of glycemic control and vascular complications in type 2 diabetic patients. In this case control study, serum for 122 samples was analyzed using ELISA for the presence of anti-Toxoplasma- IgG-antibodies (Abs) in both type 2 diabetic patients (62) and controls (60). A1c titer (level of diabetic control) was estimated in all diabetic cases. Full history and examination were performed after all contributors' consents. Anti-Toxoplasma IgG-Abs were detected in 56.45 % of diabetic patients and in 36.67% of the controls. Toxoplasmosis was significantly found more prevalent in diabetics associated with hypertension than controls (P=0.005). Among diabetics, patients with positive anti T. gondii IgG have significant long duration of diabetes versus those with negative anti T. gondii IgG (7.14±2.962 vs.3.26±1.583 years, respectively; P < 0.001). No relations were found between types of diabetic vascular complication, level of glycemic control based on HbA1c level and occurrence of toxoplasmosis. We concluded that despite of high prevalence of anti T. gondii IgG in diabetic patients, it has no relation to diabetic complication and glycemic control.
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January 2020

Evidences of brain and lung invasion of a local water Cryptosporidium parvum isolate in comparison to Iowa strain: serological and immunohistochemical cytokine evaluation.

Ann Parasitol 2020 ;66(3):311-318

Department of Parasitology, Faculty of Medicine, Assiut University, Major General Ahmed Kamel Street, Al-Qasr Road, Assiut 71515, Egypt.

Cryptosporidium spp. is an obligate intracellular parasite that has become a community threat. The pathological consequences of cryptosporidiosis vary not only in different Cryptosporidium species but even among different isolates of the same species. The present study aimed to track the serological and immunohistopathological differences between animals infected by Cryptosporidium parvum "Iowa isolate" (CPI) and Cryptosporidium parvum "water isolate" isolated from a local water supply in Assiut Governorate, Egypt (CPW). Three experimental groups were encountered: negative control group (C), the CPI group and the CPW group; each contains ten Swiss albino mice. Serum cytokine: IL10 and TNF-α were measured. Expression of Cryptosporidium antigen and CD3 in the intestinal, pulmonary and brain tissue were evaluated through immunohistochemical assay. IL10 and TNF-α were elevated in both infected groups, over expression of Cryptosporidium protein and CD3 in the intestinal, pulmonary and brain tissue in CPW infected group compared to Iowa infected one. Multi-organs affection occurred in the CPW indicating more severe pathogenicity and virulence than standard Iowa isolate. The local C. parvum isolate was more virulent than tested Iowa isolate as it spread extra-intestinally to reach brain tissue.
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http://dx.doi.org/10.17420/ap6603.269DOI Listing
November 2020

Adaptive thermogenesis enhances the life-threatening response to heat in mice with an Ryr1 mutation.

Nat Commun 2020 10 9;11(1):5099. Epub 2020 Oct 9.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.

Mutations in the skeletal muscle Ca release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to Ca driven increases in muscle metabolism. Lactate increases brown adipogenesis in both mouse and human brown preadipocytes. This study suggests that simple lifestyle modifications such as avoiding extreme temperatures and maintaining thermoneutrality could decrease the risk of life-threatening responses to heat and exercise in individuals with RYR1 pathogenic variants.
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http://dx.doi.org/10.1038/s41467-020-18865-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547078PMC
October 2020

Ada-WHIPS: explaining AdaBoost classification with applications in the health sciences.

BMC Med Inform Decis Mak 2020 10 2;20(1):250. Epub 2020 Oct 2.

Birmingham City University, Curzon Street, Birmingham, B5 5JU, UK.

Background: Computer Aided Diagnostics (CAD) can support medical practitioners to make critical decisions about their patients' disease conditions. Practitioners require access to the chain of reasoning behind CAD to build trust in the CAD advice and to supplement their own expertise. Yet, CAD systems might be based on black box machine learning models and high dimensional data sources such as electronic health records, magnetic resonance imaging scans, cardiotocograms, etc. These foundations make interpretation and explanation of the CAD advice very challenging. This challenge is recognised throughout the machine learning research community. eXplainable Artificial Intelligence (XAI) is emerging as one of the most important research areas of recent years because it addresses the interpretability and trust concerns of critical decision makers, including those in clinical and medical practice.

Methods: In this work, we focus on AdaBoost, a black box model that has been widely adopted in the CAD literature. We address the challenge - to explain AdaBoost classification - with a novel algorithm that extracts simple, logical rules from AdaBoost models. Our algorithm, Adaptive-Weighted High Importance Path Snippets (Ada-WHIPS), makes use of AdaBoost's adaptive classifier weights. Using a novel formulation, Ada-WHIPS uniquely redistributes the weights among individual decision nodes of the internal decision trees of the AdaBoost model. Then, a simple heuristic search of the weighted nodes finds a single rule that dominated the model's decision. We compare the explanations generated by our novel approach with the state of the art in an experimental study. We evaluate the derived explanations with simple statistical tests of well-known quality measures, precision and coverage, and a novel measure stability that is better suited to the XAI setting.

Results: Experiments on 9 CAD-related data sets showed that Ada-WHIPS explanations consistently generalise better (mean coverage 15%-68%) than the state of the art while remaining competitive for specificity (mean precision 80%-99%). A very small trade-off in specificity is shown to guard against over-fitting which is a known problem in the state of the art methods.

Conclusions: The experimental results demonstrate the benefits of using our novel algorithm for explaining CAD AdaBoost classifiers widely found in the literature. Our tightly coupled, AdaBoost-specific approach outperforms model-agnostic explanation methods and should be considered by practitioners looking for an XAI solution for this class of models.
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http://dx.doi.org/10.1186/s12911-020-01201-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531148PMC
October 2020

Enhancement of the Molecular and Serological Assessment of Hepatitis E Virus in Milk Samples.

Microorganisms 2020 Aug 12;8(8). Epub 2020 Aug 12.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.

Hepatitis E virus (HEV) infection is endemic in developing and developed countries. HEV was reported to be excreted in the milk of ruminants, raising the possibility of transmission of HEV infection through the ingestion of contaminated milk. Therefore, the detection of HEV markers in milk samples becomes pivotal. However, milk includes inhibitory components that affect HEV detection assays. Previously it was reported that dilution of milk matrix improves the performance of HEV molecular assay, however, the dilution of milk samples is not the best strategy especially when the contaminated milk sample has a low HEV load. Therefore, the objective of this study is to compare the effect of extraction procedures on the efficiency of HEV RNA detection in undiluted milk samples. In addition, we assessed the effect of the removal of milk components such as fats and casein on the performance of the molecular and serological assays of HEV. Phosphate buffered saline (PBS) and different milk matrices (such as whole milk, skim milk, and milk serum) were inoculated with different HEV inoculums and subjected to two different extraction procedures. Method A includes manual extraction using spin column-based extraction, while method B includes silica-based automated extraction. Method A was more sensitive than method B in the whole milk and skim milk matrices with a LoD of 300 IU/mL, and virus recovery yield of 47%. While the sensitivity and performance of method B were significantly improved using the milk serum matrix, with LoD of 96 IU/mL. Interestingly, retesting HEV positive milk samples using the high sensitivity assay based on method B extraction and milk serum matrix increased the HEV RNA detection rate to 2-fold. Additionally, the performance of HEV serological assays such as anti-HEV IgG and HEV Ag in the milk samples was improved after the removal of the fat globules from the milk matrix. In conclusion, HEV RNA assay is affected by the components of milk and the extraction procedure. Removal of inhibitory substances, such as fat and casein from the milk sample increased the performance of HEV molecular and serological assays which will be suitable for the low load HEV milk with no further dilutions.
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http://dx.doi.org/10.3390/microorganisms8081231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465259PMC
August 2020

Replication of Hepatitis E Virus (HEV) in Primary Human-Derived Monocytes and Macrophages In Vitro.

Vaccines (Basel) 2020 May 21;8(2). Epub 2020 May 21.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.

HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations.
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http://dx.doi.org/10.3390/vaccines8020239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349946PMC
May 2020

Joint remodeling outcome of serum levels of Dickkopf-1 (DKK1), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type II collagen (CTXII) in rheumatoid arthritis.

Cent Eur J Immunol 2020 ;45(1):73-79

Department of Rheumatology, Rehabilitation and Physical Medicine, Assiut University Hospital, Assiut, Egypt.

Introduction: Rheumatoid arthritis (RA) is the most widespread chronic inflammatory rheumatic disease over the world. It is characterized by chronic proliferation of synovium, cartilage destruction, and periarticular erosion/bone loss. We investigated the serum levels of the C-telopeptide of type II collagen (CTX-II), Dickkopf-1 (DKK1), and cartilage oligomeric matrix protein (COMP) in relationship to the disease activity.

Material And Methods: Serum COMP, CTX-II, and DKK1 levels were measured in 63 RA patients and 50 person age and gender matched as a healthy controls by ELISA test. Disease activity score (DAS) were calculated.

Results: The mean level of and COMP and CTX-II were significantly higher in patients with RA than in healthy controls (5.71 ±7.04 vs. 2.70 ±1.31 ng/ml, and 0.45 ±0.27 vs. 0.23 ±0.16 ng/ml, respectively; p < 0.001). Also, DKK1 serum levels were significantly higher in patients with RA than in healthy controls (6970.68 ±7566.68 vs. 3276.96 ±1306.77 pg/m; p < 0.001). There was a positive significant correlation between DKK1 and swollen joint (r = 0.42, p < 0.001). There were no significant differences in the number of patients, gender, the duration of RA disease, DAS, and RF. Sensitivity was 58.7% and specificity was 85.7% at a cut-off point (> 3.6 ng/ml) for serum COMP in RA patients, while, sensitivity was 100% and specificity was 52.4% at a cut-off point (> 0.15 ng/ml) for serum CTX-II and sensitivity was 68.3% and specificity was 95.2 % at a cut-off point (> 4876 pg/ml) for serum DKK1.

Conclusions: Measurement of some serological biomarkers such as CTX-II, COMP, and DKK1 that reflect bone and cartilage destruction in RA patients could be used to indicate disease activity and early joint affection.
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http://dx.doi.org/10.5114/ceji.2020.94685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226550PMC
January 2020

Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles.

Colloids Surf B Biointerfaces 2020 Apr 25;192:110997. Epub 2020 Apr 25.

Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences & Technology (HST), Cambridge, MA 02139, USA. Electronic address:

Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110997DOI Listing
April 2020

In-vitro evaluation of copper/copper oxide nanoparticles cytotoxicity and genotoxicity in normal and cancer lung cell lines.

J Trace Elem Med Biol 2020 Jul 27;60:126481. Epub 2020 Feb 27.

Biophysics Department, Faculty of Science, Cairo University, Egypt; Faculty of Engineering, British University in Egypt (BUE), Egypt.

Background: Nanotoxicology is a major field of study that reveals hazard effects of nanomaterials on the living cells.

Methods: In the present study, Copper/Copper oxide nanoparticles (Cu/CuO NPs) were prepared by the chemical reduction method and characterized by different techniques such as: X-Ray Diffraction, Transmission and Scanning Electron Microscopy. Evaluation of the toxicity of Cu/CuO NPs was performed on 2 types of cells: human lung normal cell lines (WI-38) and human lung carcinoma cell (A549). To assess the toxicity of the prepared Cu/CuOs NPs, the two cell types were exposed to Cu/CuO NPs for 72 h. The half-maximal inhibitory concentration IC of Cu/CuO NPs for both cell types was separately determined and used to examine the cell genotoxicity concurrently with the determination of some oxidative stress parameters: nitric oxide, glutathione reduced, hydrogen peroxide, malondialdehyde and superoxide dismutase.

Results: Cu/CuO NPs suppressed proliferation and viability of normal and carcinoma lung cells. Treatment of both cell types with their IC's of Cu/CuO NPs resulted in DNA damage besides the generation of reactive oxygen species and consequently the generation of a state of oxidative stress.

Conclusion: Overall, it can be concluded that the IC's of the prepared Cu/CuO NPs were cytotoxic and genotoxic to both normal and cancerous lung cells.
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http://dx.doi.org/10.1016/j.jtemb.2020.126481DOI Listing
July 2020

Induction of Apoptosis by Nano-Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells.

Anticancer Agents Med Chem 2020 Feb 3. Epub 2020 Feb 3.

Chemistry Department, Faculty of Science, Tanta University, Tanta 31527. Egypt.

Background: Chemotherapy is currently the most utilized treatment for cancer. Therapeutic potential of metal complexes in cancer therapy has attracted a lot of interest. The mechanisms of action of most organometallic complexes are poorly understood.

Objective: This study was designed to explore the mechanisms governing the anti-proliferative effect of the free ligand N1,N6-bis((2-hydroxynaphthalin-1-yl)methinyl)) adipohydrazone (H2L) and its complexes of Mn(II), Co(II), Ni(II) and Cu(II).

Methods: Cells were exposed to H2L or its metal complexes where cell viability determined by MTT assay. Cell cycle was analysed by flow cytometry. In addition, qRT-PCR was used to monitor the expression of Bax and Bcl-2. Moreover, molecular docking was carried out to find the potentiality of Cu(II) complex as an inhibitor of Adenosine Deaminase (ADA). ADA, Superoxide Dismutase (SOD) and reduced Glutathione (GSH) levels were measured in the most affected cancer cell line.

Results: The obtained results demonstrated that H2L and its Cu(II) complex exhibited a strong cytotoxic activity compared to other complexes against HepG2 cells (IC50 = 4.14±0.036μM/ml and 3.2±0.02μM/ml), respectively. Both H2L and its Cu(II) complex induced G2/M phase cell cycle arrest in HepG2 cells. Additionally, they induced apoptosis in HepG2 cells via upregulation of Bax and downregulation of Bcl-2. Interestingly, the activity of ADA was decreased by 2.8 fold in HepG2 cells treated with Cu(II) complex compared to untreated cells. An increase of SOD activity and GSH level in HepG2 cells compared to control was observed.

Conclusion: The results concluded that Cu(II) complex of H2L induced apoptosis in HepG2 cells. Further studies are needed to confirm its anti-cancer effect in vivo.
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http://dx.doi.org/10.2174/1871520620666200204103756DOI Listing
February 2020

Synthesis and Design of Norfloxacin drug delivery system based on PLA/TiO nanocomposites: Antibacterial and antitumor activities.

Mater Sci Eng C Mater Biol Appl 2020 Mar 5;108:110337. Epub 2019 Nov 5.

Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO (spheres (S), rods (R). The dispersion of TiO was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO nanospheres (NOR@TiO (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.
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http://dx.doi.org/10.1016/j.msec.2019.110337DOI Listing
March 2020

Correction to: Risk stratification of pediatric high-grade glioma: a newly proposed prognostic score.

Childs Nerv Syst 2020 Apr;36(4):879

Department of Radiation Oncology, National Cancer Institute, Cairo University and Children Cancer Hospital (CCHE), Cairo, Egypt.

The original version of this article unfortunately contained an error. The author apologizes for having provided an incorrect name: "Mohamed S. Zaghluol" should be "Mohamed S. Zaghloul". Given in this article is the correct author name.
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http://dx.doi.org/10.1007/s00381-019-04473-wDOI Listing
April 2020

Examination of the interaction between method of anesthesia and shunting with carotid endarterectomy.

J Vasc Surg 2020 06 4;71(6):1964-1971. Epub 2019 Nov 4.

Division of Vascular and Endovascular Surgery, Department of Surgery, University of California San Diego, La Jolla, Calif. Electronic address:

Background: Although the choice of anesthesia during carotid endarterectomy (CEA) does not seem to increase the risk of perioperative stroke, it might affect the outcomes of shunting during CEA. This study aims to evaluate whether the choice of anesthesia modifies the association between shunting and in-hospital stroke/death after CEA.

Methods: We retrospective reviewed all CEA cases performed between 2003 and 2017 in the Vascular Quality Initiative. Patients were divided into three groups: (1) no shunting during CEA (n = 29,227 [48.4%]), (2) routine shunting (n = 28,673 [47.5%]), and (3) selective shunting based on an intraoperative indication (n = 2499 [4.1%]). Multivariable logistic regression analysis was used to study the interaction between anesthesia (local anesthesia [LA]/regional anesthesia [RA] vs general anesthesia [GA]) and intraoperative shunting (no shunting vs routine and selective shunting) during CEA in predicting the risk of in-hospital stroke/death after CEA.

Results: The final cohort included 60,399 patients. The majority of CEA cases (90.2%) were performed under GA. Of the study cohort, 29,227 (48.4%) underwent CEA without shunting, 28,673 patients (47.5%) had routine shunting, and the remaining (n = 2499 [4.1%]) were selectively shunted. The interaction between intraoperative shunting and anesthesia in predicting in-hospital stroke/death was statistically significant (P < .05). When CEA is performed under LA/GA, routine shunting was associated with 3.5 times the adjusted odds of in-hospital stroke/death after CEA (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P < .001) compared with no shunting, whereas selective shunting was associated with 7.1 the odds (OR, 7.1; 95% CI, 3.5-14.7; P < .001). In contrast, under GA, there was no significant association between routine shunting and in-hospital stroke/death (OR, 1.2; 95% CI, 1.0-1.5; P = .12), whereas selective shunting was associated with 1.7 times the odds (OR, 1.7; 95% CI, 1.2-2.4; P < .01) compared with not performing shunting during CEA.

Conclusions: The use of LA/RA is associated with increased odds of stroke/death compared with GA when intraoperative shunting is performed. The effect of anesthesia is more pronounced in patients who develop clamp-related ischemia and undergo selective shunting. More controlled studies are needed to explain these findings and validate them.
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http://dx.doi.org/10.1016/j.jvs.2019.08.248DOI Listing
June 2020

Differentiation of Heterogeneous Radiation Exposure Using Hematology and Blood Chemistry.

Radiat Res 2020 01 31;193(1):24-33. Epub 2019 Oct 31.

Department of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.

In the aftermath of a nuclear incident, survivors will suffer the deleterious effects from acute radiation exposure. The majority of those affected would have received heterogeneous radiation exposure, reflected in hematological metrics and blood chemistry. Here, we investigated the acute and long-term changes in kinetics and magnitude of pancytopenia and blood chemistry in rats irradiated using varying degrees of body shielding. We hypothesized that, although a single blood count may not be able to differentiate the degree of radiation exposure, a combination of measurements from complete blood cell counts (CBCs) and blood chemistry tests is able to do so. Male Sprague Dawley rats, 8-10 weeks of age, received single-dose 7.5 Gy (160 kVp, 25 mA, 1.16 Gy/min) whole-body irradiation (WBI, LD) or partial-body irradiation (PBI), as follows: one leg shielded (1LS, LD), two legs shielded (2LS, LD) or the upper half of the body shielded (UHS, LD). Animal morbidity and weights were measured. Blood was drawn at 1, 5, 10, 20 and 30 days postirradiation (n = 4-11). For kidney and liver function measurements, CBC and blood chemistry analyses were performed. WBI animals on average survived 9 ± 0.4 days postirradiation. In contrast, all PBI animals survived the 30-day study period. CBC analysis revealed that both white blood cell (WBC) and platelet counts were most affected after irradiation. While WBC counts were significantly lower in all irradiated groups on days 1, 5 and 10, platelets were only significantly lower on days 5 and 10 postirradiation. In addition, on day 5 postirradiation both WBC and platelet counts were able to differentiate WBI (non-survivors) from PBI 2LS and UHS animals (survivors). Using four blood parameters (platelets, percentage lymphocytes, percentage neutrophils and percentage monocytes) on day 5 after 7.5 Gy irradiation and a linear discrimination analysis (LDA), we were able to predict the degree of body exposure in animals with a 95.8% accuracy. Alkaline phosphatase (ALP) was significantly lower in all groups on days 5 and 10 postirradiation compared to baseline. Furthermore, ALP was significantly higher in the UHS than WBI animals. The AST:ALT ratio was significantly higher than baseline in all irradiated groups on day 1 postirradiation. In conclusion, four CBC parameters, on day 5 after receiving a 7.5 Gy dose of radiation, can be employed in a LDA to differentiate various degrees of exposure (shielding). The characterization presented in this work paves the way for further studies in differences caused by heterogeneous body exposure to radiation and a new metric for biodosimetry.
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http://dx.doi.org/10.1667/RR15411.1DOI Listing
January 2020

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as independent predictors of outcome in infective endocarditis (IE).

Egypt Heart J 2019 Sep 18;71(1):13. Epub 2019 Sep 18.

Cardiovascular Medicine Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.

Background: Early and accurate risk assessment is an important clinical demand in patients with infective endocarditis (IE). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent predictors of prognosis in many infectious and cardiovascular diseases. Very limited studies have been conducted to evaluate the prognostic role of these markers in IE.

Results: We analyzed clinical, laboratory, and echocardiographic data and outcomes throughout the whole period of hospitalization for a total of 142 consecutive patients with definitive IE. The overall in-hospital mortality was 21%. Major complications defined as central nervous system embolization, fulminant sepsis, acute heart failure, acute renal failure, and major artery embolization occurred in 38 (27%), 34 (24%), 32 (22.5%), 40 (28%), and 90 (63.4%) patients, respectively. The NLR, total leucocyte count (TLC), neutrophil percentage, creatinine, and C-reactive protein (CRP) level obtained upon admission were significantly higher in the mortality group [p ≤ 0.001, p = 0.008, p = 0.001, p = 0.004, and p = 0.036, respectively]. A higher NLR was significantly associated with fulminant sepsis and major arterial embolization [p = 0.001 and p = 0.028, respectively]. The receiver operating characteristic (ROC) curve of the NLR for predicting in-hospital mortality showed that an NLR > 8.085 had a 60% sensitivity and an 84.8% specificity for an association with in-hospital mortality [area under the curve = 0.729, 95% confidence interval (CI) 0.616-0.841; p = 0.001]. The ROC curve of the NLR for predicting severe sepsis showed that an NLR > 5.035 had a 71.8% sensitivity and a 68.5% specificity for predicting severe sepsis [area under the curve 0.685, 95% CI 0.582-0.733; p = 0.001]. The PLR showed no significant association with in-hospital mortality or in-hospital complications.

Conclusion: A higher NLR, TLC, neutrophil percentage, creatinine level, and CRP level upon admission were associated with increased in-hospital mortality and morbidity in IE patients. Furthermore, a lower lymphocyte count/percentage and platelet count were strong indicators of in-hospital mortality among IE patients. Calculation of the NLR directly from a CBC upon admission may assist in early risk stratification of patients with IE.
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http://dx.doi.org/10.1186/s43044-019-0014-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821428PMC
September 2019

A comprehensive preclinical assessment of late-term imaging markers of radiation-induced brain injury.

Neurooncol Adv 2019 May-Dec;1(1):vdz012. Epub 2019 Jul 2.

Department of Pediatrics, Hematology-Oncology Section, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.

Background: Cranial radiotherapy (CRT) is an important part of brain tumor treatment, and although highly effective, survivors suffer from long-term cognitive side effects. In this study we aim to establish late-term imaging markers of CRT-induced brain injury and identify functional markers indicative of cognitive performance. Specifically, we aim to identify changes in executive function, brain metabolism, and neuronal organization.

Methods: Male Sprague Dawley rats were fractionally irradiated at 28 days of age to a total dose of 30 Gy to establish a radiation-induced brain injury model. Animals were trained at 3 months after CRT using the 5-choice serial reaction time task. At 12 months after CRT, animals were evaluated for cognitive and imaging changes, which included positron emission tomography (PET) and magnetic resonance imaging (MRI).

Results: Cognitive deficit with signs of neuroinflammation were found at 12 months after CRT in irradiated animals. CRT resulted in significant volumetric changes in 38% of brain regions as well as overall decrease in brain volume and reduced gray matter volume. PET imaging showed higher brain glucose uptake in CRT animals. Using MRI, irradiated brains had an overall decrease in fractional anisotropy, lower global efficiency, increased transitivity, and altered regional connectivity. Cognitive measurements were found to be significantly correlated with six image features that included myelin integrity and local organization of the neural network.

Conclusions: These results demonstrate that CRT leads to late-term morphological changes, reorganization of neural connections, and metabolic dysfunction. The correlation between imaging markers and cognitive deficits can be used to assess late-term side effects of brain tumor treatment and evaluate efficacy of new interventions.
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http://dx.doi.org/10.1093/noajnl/vdz012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777502PMC
July 2019

Boronic-targeted albumin-shell oily-core nanocapsules for synergistic aromatase inhibitor/herbal breast cancer therapy.

Mater Sci Eng C Mater Biol Appl 2019 Dec 19;105:110099. Epub 2019 Aug 19.

Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences & Technology (HST), Cambridge, MA 02139, USA. Electronic address:

Multi-modality strategies of albumin-mediated drug accumulation in tumor, boronate-based active tumor targeting and synergistic cancer therapy were combined together for effective treatment of breast cancer. Herein we report the development of albumin-shell oily-core nanocapsules (NCs), loaded with novel combination of hydrophobic drugs, exemestane (EXE) and hesperetin (HES), for targeted breast cancer therapy. This protein-lipid nanohybrid carrier was successfully fabricated using a simple protein-coating method based on the electrostatic adsorption of negatively charged albumin shell onto the oily core containing cationic surfactant. While EXE was directly encapsulated into the oily core, HES was pre-formulated in the form of phospholipid complex before solubilization in oily phase. In addition to albumin-mediated binding to albondin and SPARC, phenylboronic acid was chemically coupled to the albumin shell to confer additional tumor targeting. The targeted nanocarrier (TNC) demonstrated enhanced internalization into MCF-7 breast cancer cells resulting in synergistic cytotoxic activity with a combination index (CI) of 0.662 and dose reduction index (DRI) of 8.22 and 1.84 for EXE and HES, respectively. In vivo, TNC displayed superior anti-cancer activity in tumor-bearing mice compared to their non-targeted counterparts and the free drug combination. A significant reduction of both tumor volume (7-folds) and Ki67 expression (3-folds) was obtained by the targeted nanocarriers compared to positive control. Overall, the boronic-targeted albumin NCs offer a promising platform for hydrophobic drug combination against cancer therapy.
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http://dx.doi.org/10.1016/j.msec.2019.110099DOI Listing
December 2019

Image-based Classification of Tumor Type and Growth Rate using Machine Learning: a preclinical study.

Sci Rep 2019 08 29;9(1):12529. Epub 2019 Aug 29.

Department of Bioengineering, Rice University, 6500 Main Street, Suite 1030, Houston, TX, 77030, USA.

Medical images such as magnetic resonance (MR) imaging provide valuable information for cancer detection, diagnosis, and prognosis. In addition to the anatomical information these images provide, machine learning can identify texture features from these images to further personalize treatment. This study aims to evaluate the use of texture features derived from T-weighted post contrast scans to classify different types of brain tumors and predict tumor growth rate in a preclinical mouse model. To optimize prediction models this study uses varying gray-level co-occurrence matrix (GLCM) sizes, tumor region selection and different machine learning models. Using a random forest classification model with a GLCM of size 512 resulted in 92%, 91%, and 92% specificity, and 89%, 85%, and 73% sensitivity for GL261 (mouse glioma), U87 (human glioma) and Daoy (human medulloblastoma), respectively. A tenfold cross-validation of the classifier resulted in 84% accuracy when using the entire tumor volume for feature extraction and 74% accuracy for the central tumor region. A two-layer feedforward neural network using the same features is able to predict tumor growth with 16% mean squared error. Broadly applicable, these predictive models can use standard medical images to classify tumor type and predict tumor growth, with model performance, varying as a function of GLCM size, tumor region, and tumor type.
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http://dx.doi.org/10.1038/s41598-019-48738-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715812PMC
August 2019

Antiprotozoal activity of silver nanoparticles against Cryptosporidium parvum oocysts: New insights on their feasibility as a water disinfectant.

J Microbiol Methods 2019 10 22;165:105698. Epub 2019 Aug 22.

Public Health and Community Medicine Department, Assiut University, 71526, Egypt.

Cryptosporidium is a protozoan of extremely medical and veterinary impact; whose oocysts donate a considerable resistant to the water treatment processes. Therefore, this study aimed to explore the impacts of silver nanoparticles (AgNPs) on count and viability of the Cryptosporidium parvum (CP) isolated from different tap water samples. The oocysts were exposed to AgNPs at different dosages of 0.05, 0.1 and 1 ppm for several contact times (30 min to 4 h). The results showed a significant decrease in oocyst count and viability in a dose-dependent manner. Additionally, AgNPs at a conc. of 1 ppm for 30 min and 0.1 ppm for 1 h reduced the oocysts by 97.2 and 94.4%, respectively. Comparatively, there was a noticeable increase in the oocyst's viability at 2 and 4 h, which emphasized that the time of contact between AgNPs and CP was not a major influencing factor for successful application of AgNPs in the nano-water treatment.
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http://dx.doi.org/10.1016/j.mimet.2019.105698DOI Listing
October 2019

Does vitamin D status correlate with insulin resistance in obese prediabetic patients? An Egyptian multicenter study.

Diabetes Metab Syndr 2019 Sep - Oct;13(5):2813-2817. Epub 2019 Jul 29.

Faculty of Science and Engineering, School of Engineering, University of Plymouth, Plymouth, PL4 8AA, UK; Branch of Biotechnology, Department of Biology, College of Science, Mustansiriyah University, POX, 10244, Baghdad, Iraq. Electronic address:

Background: The link between Vitamin-D deficiency and type 2 diabetes (T2D) is well-established. Since prediabetic obese populations have the greatest risk to develop to T2D, it was important in our study to examine serum 25(OH) D3 concentration among prediabetic obese patients and to evaluate the correlation between serum level of vitamin D and BMI, FBS, HOMA IR and HbA1c among prediabetes patients.

Methods: A multicenter case control study was carried out among 101 prediabetic persons & 50 controls, after obtaining consent from subjects and clearance from institutional ethics committee. Serum vitamin D level, Plasma levels of glycosylated hemoglobin (HbA1c) and fasting insulin levels were measured by ELISA in both groups enrolled in the study.

Results: The prevalence of vitamin-D deficiency/insufficiency was (73.3%) (n = 74) among 101 prediabetic obese individuals. Also, A significant inverse correlation was observed between vitamin D levels & body mass index(r = - 0.28, P = 0.004); fasting blood sugar (r = - 0.22, P = 0.002); HOMA insulin resistance (r = - 0.25 P = 0.01); HbA1C (r = - 0.2, P= 0.004).

Conclusions: High prevalence of vitamin D deficiency exists among obese prediabetic individuals and there is significant inverse correlation between BMI, FBS, HOMA IR, HbA1c and vitamin D level.
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http://dx.doi.org/10.1016/j.dsx.2019.07.043DOI Listing
February 2020

Risk stratification of pediatric high-grade glioma: a newly proposed prognostic score.

Childs Nerv Syst 2019 12 19;35(12):2355-2362. Epub 2019 Jun 19.

Department of Radiation Oncology, National Cancer Institute, Cairo University and Children Cancer Hospital (CCHE), Cairo, Egypt.

Objectives: High-grade glioma (HGG) is a clinical challenge. Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG-RPA) for HGG remains the standard for assessing the prognosis of adult HGG. This study assesses the validity of the RTOG-RPA to be applied to pediatric HGG.

Methods: A retrospective study was conducted on 59 pediatric HGG treated in the Children's Cancer Hospital, Egypt (CCHE) between 2007 and 2016. Several factors were studied as predictors for the disease survival, including age, gender, increased intracranial hypertension, tumor characteristics and pathology, CSF seeding, performance status, post-surgical residual, and radiation dose. The statistically significant results were integrated into a Cox-regression model to develop a prognostic risk score.

Results: Kaplan-Meier statistics identified 13 factors that impacted the overall survival. However, Cox model showed that the histological grade IV [HR 14.2, 95%CI; (3.5-57), P < 0.0001], thalamic infiltration [HR 8.7; 95%CI; (2.9-25.9), P < 0.0001], PS ≥ 60 [HR 0.317; 95%CI; (0.13-0.776); P = 0.012], and maximum tumor dimension > 3.3 cm [HR 10.2; 95%CI; (1.58-65.89); P = 0.015] were the independent variables that predicted the overall survival. A risk score was proposed based on the presence of one or more of these factors. The median OS for the low risk (score 0-1), the intermediate-low risk (score 2), the intermediate-high risk (score 3), and the high risk (score 4) were 40, 18.5, 9.5, and 2.5 months, respectively, (P < 0.0001).

Conclusion: The proposed model and risk score could stratify pediatric patients as the RTOG-RPA do for the adults.
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http://dx.doi.org/10.1007/s00381-019-04257-2DOI Listing
December 2019

Erector spine block: a new indication for postoperative pain in gynecological surgeries?

Minerva Anestesiol 2019 10 21;85(10):1140-1141. Epub 2019 May 21.

Department of Anesthesiology, Augusta University, Augusta, GA, USA -

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http://dx.doi.org/10.23736/S0375-9393.19.13672-3DOI Listing
October 2019

Synthesis, Structural Characterization, Molecular Modeling and DNA Binding Ability of CoII, NiII, CuII, ZnII, PdII and CdII Complexes of Benzocycloheptenone Thiosemicarbazone Ligand.

Mini Rev Med Chem 2019 ;19(13):1068-1079

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Background & Objective: Six novel complexes of transition metal namely, [CoLCl2(H2O)2]0.5H2O, [NiLCl2(H2O)2]0.5H2O, [CuLCl2]0.5H2O, [ZnLCl2], [PdLCl2]H2O and [CdLCl2]H2O, where L is benzocycloheptenone thiosemicarbazone ligand, have been obtained. The confirmation of the structures of the obtained metal chelates depends on the different spectral and physicochemical techniques including CHN analysis, infrared spectra, molar conductivity measurement, UV-vis, thermogravimetric analysis and magnetic moment. The infrared spectral results ascertained that the ligand behaved as neutral bidentate connecting the metal centers via N and S atoms of C=N and C=S groups, respectively.

Methods: The UV-Vis, molar conductivity and magnetic susceptibility results implied that the geometrical structures of the metal chelates are octahedral for Co(II) & Ni(II) complexes, tetrahedral for Zn(II) & Cd(II) complexes and square planar for Cu(II) & Pd(II) complexes which have been confirmed by molecular modeling studies.

Conclusion: Moreover, the mode of interaction between some chosen metal complexes towards SSDNA has been thoughtful by UV-Vis spectra and viscosity measurements. The value of the intrinsic binding constant (Kb) for the examined compounds has been found to be lower than the binding affinity of the classical intercalator ethedium bromide. Also, the viscosity measurements of the complexes proved that they bind to DNA, most likely, by a non-intercalative mode like H-bonding or electrostatic interactions.
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http://dx.doi.org/10.2174/1389557519666190301143322DOI Listing
October 2019

High Improvement in Lactic Acid Productivity by New Alkaliphilic Bacterium Using Repeated Batch Fermentation Integrated with Increased Substrate Concentration.

Biomed Res Int 2019 17;2019:7212870. Epub 2019 Jan 17.

Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, P.N.:11884, Nasr City, Cairo, Egypt.

Optically pure lactic acid (LA) is an important chemical platform that has a wide range of industrial and biotechnological applications. Improved parameters for cost effective LA production are of great interest for industrial developments. In the present study, an alkaliphilic lactic acid bacterium, BoM 1-2, was selected among 369 newly obtained bacterial isolates. It was characterized using API 50 CHL kit and identified as BoM 1-2 by 16S rRNA gene sequence analysis. Efficient polymer-grade L-lactic acid production was achieved at pH 9.0 and 40°C. In batch fermentation strategy using 20 g L glucose, 19.6 g L lactic acid was obtained with volumetric productivity of 2.18 g Lh. While using 100 g L glucose, 96.0 g L lactic acid was obtained with volumetric productivity of 1.07 g Lh The highest lactic acid concentration of 180.6 g L was achieved in multipulse fed batch strategy with volumetric productivity of 0.65 g Lh. To achieve higher productivity, repeated fermentation processes were applied using the two different strategies. In the first strategy, the lactic acid productivity was increased from 1.97 g Lh to 4.48 g Lh when the total of 10 repeated runs were carried out using 60 g L glucose, but lactic acid productivity decreased to 2.95 g Lh using 100 g L glucose. In second strategy, repeated fermentation coupled with gradual increase in glucose concentration from 40 to 100 g L was conducted for 24 runs. A dramatic increase in LA productivity up to 39.9 g Lh (18-fold compared to first run) was achieved using 40 g L glucose while volumetric productivity ranging between 24.8 and 29.9 g Lh was achieved using 60-100 g L glucose.
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http://dx.doi.org/10.1155/2019/7212870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354166PMC
May 2019