Vitamin D Receptor Gene (Fok-I) Polymorphisms in Type 1 Diabetic Children; Case Study in Zagazig University Hospitals

Background: Many meta-analyses studied the association between vitamin D receptor (VDR) gene polymorphism and type 1 diabetes (T1DM) susceptibility. Objective: This study was designed to assess the role of VDR gene (FOK-I) polymorphisms in type 1 diabetic children from Zagazig University Hospitals in Egypt. Patients and Method: In this case-control study, the genotypes of VDR gene (FOK-I) polymorphisms were assessed in 180 type 1 diabetic children and 120 healthy matched age controls by PCR-RFLP analysis. Results: A high statistical difference between patient and control regarding VDR gene (FOK-I) polymorphisms, where 44% of the patient group had heterozygous genotype (AG) compared to 8.3% in the control group. AG genotype has almost a higher risk nine times odds ratio (OR) = 8.8 than AA genotype in diabetic patients. There was a significant increase in the G allele in the patient group. Moreover, a significant association between (FOK-I) polymorphisms and T1DM complications was also observed. Conclusion: (AG) genotype of VDR gene (FOK-I) polymorphisms could be a risk factor for T1DM complications. So, VDR gene (FOK-I) polymorphisms should be performed with other genetic studies for early prediction, detection and prevention of microvascular complications of T1DM that adversely affect health-related quality of life of Egyptian children and burden the primary care units

Sperm abnormality toxicity due to cyclosporine A and the ameliorative effect of royal jelly in male rats

The immunosuppressive drug, utilized widely in Egypt, cyclosporine A was studied to evaluate its toxicity in male rats. Animals were divided into a control (untreated), 3 groups treated intraperitoneally with 20, 40 and 60 m/kg cyclosporine A for 5, 10 and 15 days, respectively and 3 groups treated intraperitoneally with 20, 40 and 60 mg/kg of cyclosporine A plus 100 mg/kg royal jelly administrated orally. Toxicity evaluation was carried out using two main endpoints: reproductive study (sperm morphology and count abnormalities) and biochemical changes in liver and testis (DNA amounts). The aim of this work is to study the protective role of royal jelly against sperm abnormalities in shape and count, and changes in DNA contents in liver and testis tissue induced in rats when treated by cyclosporine A with different doses (20–40–60 mg/kg/day) for 5, 10, and 15 days in male rats and how the royal jelly can repair this changes. Our results showed that sperm abnormalities induced by cyclosporine A included deviation from normal shape in head and tail. Abnormal heads contained amorphous head and banana-shaped head, whereas the abnormal tails included divided and coiled tails. It also induced an insignificant effect on the total sperm counts after 5 days of injection with the drug combined with royal jelly. DNA contents were determined in rat liver and testis cells to illustrate the mutagenic effect of cyclosporine A and how the royal jelly can modulate this effect. From these results we concluded that cyclosporine A toxicity was dose and time dependent and should be administrated under special precautions and medical supervision. Using of royal jelly in combination with cyclosporine A drug decreased its toxic effect, so it's considered as protector

Mosquito abundance and physicochemical characteristics of their breeding water in El-Fayoum Governorate, Egypt

Objectives: This study was conducted to identify the mosquito species and the physicochemical characteristics of their breeding sites in six districts in El-Fayoum Governorate, Egypt, during October and November 2020. Methods: Using the dipping method, mosquito larvae were collected from forty-two different breeding sites, including irrigation channels, canals, agricultural puddles, sewage tanks, stagnant water puddles, and swamps. Water temperature, pH, alkalinity, nitrite, chloride, electrical conductivity (EC), and total dissolved solids (TDS) were measured for all the studied breeding sites. Results: The survey revealed the presence of nine mosquito species: Culex perexiguus (Theobald, 1901), Culex pipiens (Linnaeus, 1758), Culex antennatus (Becker, 1903), Culex theileri (Theobald, 1903), Anopheles multicolor (Cambouliu, 1902), Anopheles sergentii (Theobald, 1907), Ochlerotatus caspius (Pallas, 1771), Culiseta longiareolata (Macquart, 1838), and Uranotaenia ungiculata (Edwards, 1913), representing five genera. Out of these species, Cx. pipiens is the most abundant. Oc. caspius and Cx. antennatus revealed significant positive correlations with chloride, TDS, and EC. Cx. perexiguus only showed significant positive correlations with chloride. Conclusion: Most of the recorded mosquito species are found to be able to tolerate different degrees of pollution in their breeding water. These data may contribute to establishing a database on mosquito vectors and their habitats and, hence, assist in planning and implementing the appropriate control measures in this region

Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

<div><p></p><p><i>Background.</i> Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. <i>Material and methods.</i> The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for <i>D</i>₅₀ and γ₅₀ were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. <i>Results.</i> The reference dose- response relationship for a patient without pulmonary co-morbidities, caudally located tumor, no history of smoking, < 63 years old, and receiving no sequential chemotherapy was estimated as <i>D</i>₅₀⁰ = 34.4 Gy (95% CI 30.7, 38.9), <i>γ</i>₅₀⁰ = 1.19 (95% CI 1.00, 1.43). Individual patient risk estimates were calculated. The cumulative incidences of RP in the validation dataset were not significantly different in high/low-risk patients when doing risk allocation with the QUANTEC model (p = 0.11), but were significantly different using the individualized model (p = 0.006). C-indices were significantly different between the dose-only and the individualized model. <i>Conclusion.</i> This study presents a method to combine a published dose-response function with known clinical risk factors and demonstrates the increased predictive power of the combined model. The method allows for individualization of dose constraints and individual patient risk estimates.</p></div

Clinical outcome of image-guided adaptive radiotherapy in the treatment of lung cancer patients

<div><p>ABSTRACT</p><p><b>Background.</b> Adaptive strategy with daily online tumour match is a treatment option when treating locally advanced lung cancer patients with curative intended radiotherapy (RT).</p><p><b>Material and methods.</b> Fifty-two consecutive lung cancer patients treated with soft tissue match, adaptive RT and small planning target volumes (PTV) margins were analysed. A control group of 52 consecutive patients treated with bone match, no adaptive strategy and larger margins was included. Patients were followed with computed tomography (CT) scans every third month. CT-images showing loco-regional recurrences were identified. The recurrence gross tumour volume was delineated and registered with the original radiation treatment plan to identify site of failure. All patients were toxicity-scored using CTCAE 4.03 grading scale. Data were analysed using the Kaplan-Meier analysis.</p><p><b>Results.</b> The median follow-up time was 16 months (3–35). Within a year, 35% of the patients in the adaptive group (ART-group) and 53% in the control group (No-ART-group) experienced loco-regional failure, showing improved loco-regional control in the ART group (p = 0.05). One patient in the ART-group and four patients in the No-ART-group showed marginal failure. Median overall progression-free survival time for the ART-group was 10 months (95% CI 8–12), and 8 months (95% CI 6–9) for the No-ART-group. Severe pneumonitis (grade 3–5) decreased from 22% in the No-ART-group to 18% in the ART-group (non-significant, p = 0.6). No significant difference in severe dysphagia was found between the two groups.</p><p><b>Conclusion.</b> In the first small cohort of patients investigated, implementation of soft-tissue tumour match and adaptive strategies for locally advanced lung cancer patients increased the loco-regional control rate without increasing treatment-related toxicity.</p></div

New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy

<div><p>ABSTRACT</p><p><b>Background.</b> Intensity-modulated radiotherapy (IMRT) in locally advanced non-small cell lung cancer (NSCLC) allows treatment of patients with large tumour volumes, but radiation pneumonitis (RP) remains a dose limiting complication. The incidence of severe RP using three-dimensional (3D) conformal radiotherapy, was previously reported to be 17%, with 2% lethal RP. The aim of this study was to monitor the incidence of RP following the introduction of IMRT.</p><p><b>Material and methods.</b> IMRT was delivered using 4–8 beam arrangements and introduced in three phases. In phase I, 12 patients were treated using only one dose constraint (V20), in which the total lung volume receiving 20 Gy was limited to 40%. In phase II, 25 patients were treated with an additional dose constraint of mean lung dose (MLD) ≤ 20 Gy. In phase III, 50 patients were treated with an extra dose constraint (V5) in which the total lung volume receiving a dose of 5 Gy was ≤ 60%. RP was prospectively documented. The results of phase I & II (IMRT-1) were compared to those in phase III (IMRT-2).</p><p><b>Results.</b> The median follow-up time was 17 months. The introduction of IMRT was associated with an increase in the incidence of RP in Phase I&II (IMRT-1) to 41%, six of 37 (16%) had grade 5 RP (IMRT-1). Introducing the dose constraint V5, led to a significant reduction in the lung volume receiving doses ≤ 20 Gy from 51 ± 2% to 41 ± 1% (p < 0.0001). Introducing V5 constraint did not decrease the incidence of severe (grade ≥ 3) RP, but significantly decreased the lethal pneumonitis to 4% (two of 50 patients), p = 0.05.</p><p><b>Conclusion.</b> Introducing IMRT resulted in an increase in the incidence of severe and fatal RP, however a new dose constraint to the volume of lung receiving low doses reduced the incidence of lethal pneumonitis.</p></div

Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NF-κβ is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κβ inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κβp65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-α, IL-1β, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics

Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion SPECT/CT: Correlation with radiation dose and clinical morbidity

<div><p>ABSTRACT</p><p><b>Background.</b> The purpose of the study was to assess dose and time dependence of radiotherapy (RT)-induced changes in regional lung function measured with single photon emission computed tomography (SPECT) of the lung and relate these changes to the symptomatic endpoint of radiation pneumonitis (RP) in patients treated for non-small cell lung cancer (NSCLC).</p><p><b>Material and methods.</b> NSCLC patients scheduled to receive curative RT of minimum 60 Gy were included prospectively in the study. Lung perfusion SPECT/CT was performed before and three months after RT. Reconstructed SPECT/CT data were registered to treatment planning CT. Dose to the lung was segmented into regions corresponding to 0–5, 6–20, 21–40, 41–60 and > 60 Gy. Changes (%) in regional lung perfusion before and after RT were correlated with regional dose and symptomatic RP (CTC grade 2–5) outcome.</p><p><b>Results.</b> A total of 58 patients were included, of which 45 had three-month follow-up SPECT/CT scans. Analysis showed a statistically significant dose-dependent reduction in regional perfusion at three-month follow-up. The largest population composite perfusion loss was in 41–60 Gy (42.2%) and > 60 Gy (41.7%) dose bins. Lung regions receiving low dose of 0–5 Gy and 6–20 Gy had corresponding perfusion increase (-7.2% and -6.1%, respectively). Regional perfusion reduction was different in patients with and without RP with the largest difference in 21–40 Gy bin (p = 0.02), while for other bins the difference did not reach statistical significance. The risk of symptomatic RP was higher for the patients with perfusion reduction after RT (p = 0.02), with the relative risk estimate of 3.6 (95% CI 1.1–12).</p><p><b>Conclusion.</b> Perfusion lung function changes in a dose-dependent manner after RT. The severity of radiation-induced lung symptoms is significantly correlated with SPECT perfusion changes. Perfusion reduction early after RT is associated with a high risk of later development of symptomatic RP.</p></div