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Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

SummaryIn plants adverse environmental conditions can induce the accumulation of reactive oxygen species, such as singlet oxygen or hydrogen peroxide, at the level of the photosynthetic apparatus. The coordinated action of nucleus-encoded genes is required for containing the deleterious effects of reactive oxygen species. The regulation of such genes follows a molecular signalling process between the chloroplast and the nucleus called retrograde signalling. Previously, we proposed that the Topoisomerase VI (Topo VI) complex participates in the singlet oxygen stress response by regulating the expression of specific subsets of nuclear genes. However, the underlying molecular mechanisms remain unresolved. In this study, we demonstrate that the Topo VI subunit BIN4 interacts with the cohesin subunit AtSMC3. We also show that, similarly to Topo VI mutants, a line suppressing AtSMC3 shows constitutive activation of singlet oxygen response genes and enhanced tolerance to photooxidative stress. Together, these results suggest that Topo VI and AtSMC3 control the expression of singlet oxygen response genes and are possibly involved in the acclimation of plants to photooxidative stress conditions.

Background: US-based thyroid imaging lexicons have been widely used in clinical practice for identification of FNAC-eligible thyroid nodules. A “U”-classification (BTA) was introduced in 2014 with intense researches conducted in last five years trying to test its feasibility and reliability in stratification of US thyroid nodules. Material and Methods: Prospective single-center uni-departmental study aimed at selection of only “solitary” nodules with image-analysis of US features of suspicious and non-suspicious nodules and ascribing each nodule a “U”-class in view of lexicon-provided user-friendly graphic references. Results: A small cohort, of 37 solitary nodules, was selected out of a total of 150 with comparison to FNAC aspiration cytology result according to pathology Bethesda staging. The correlation of each “U” class was compared to pathology (fine needle aspirates) and revealed very good statistical significance. Conclusion: The study suggests that a BTA (The “U”- classification) is a simple reliable test that can be feasibly practiced to select FNAC-eligible nodule amongst multi-nodular glands.

Background Glomerular diseases (GDs) place a significant burden on patients and health-care systems, and they are a leading cause of end-stage renal disease (ESRD) globally. There is no national register for GDs in Egypt, and the outcomes of GDs are not extensively examined. As a result, studying GDs patterns and outcomes, as well as the association between chronic renal injury at presentation and GDs outcome, was of great interest. Methods Patients with biopsy-proven GDs, presenting to an Egyptian tertiary care center were enrolled and prospectively followed-up for 6 months, death or reaching ESRD. Chronic renal damage was assessed at diagnosis by the total renal chronicity. Results Sixty-six individuals with biopsy-confirmed GDs were enrolled in the study. The most common reasons for a renal biopsy were unexplained kidney function decrease (62%), followed by subnephrotic (23%) and nephrotic presentation (15%). The most common histological patterns were diffuse proliferative glomerulonephritis (GN), membranoproliferative GN (MPGN), and sclerosing GN. Primary and secondary GDs made up 30.3% and 69.7% of the cases, respectively. At the end of the 6-month follow-up, 28 patients had recovered their renal function, 19 had advanced to ESRD, and 7 had died. The most significant predictors of renal recovery were hemoglobin level and the total renal chronicity score. Conclusion In this tertiary care center Egyptian cohort, secondary GDs appear to be more frequent than primary GDs, diffuse proliferative GN was the most common histopathological pattern, and rapid renal recovery was not the rule in this short period. The renal chronicity score could accurately predict the renal outcome. Trial Registration: Approval for this study was granted by the Mansoura Faculty of Medicine Institutional Research Board (IRB) (approval no. MD/17.05.13).

Background: Pancreatic cancer is the fourth leading cause of cancer related deaths worldwide. It has poor prognosis especially in locally advanced tumours. Treatment of pancreatic tumours remains a challenge regarding their growth into the adjacent anatomical and vascular structures. Multidetector computed tomography (MDCT) plays an important role in diagnosing of patients with resectable and borderline resectable tumours. Evaluation of borderline resectable tumours should involve the accurate identification of the relationship between the tumour and the surrounding vessels and other vital struc-tures. Aim of Study: Evaluation of the role of CT angiography in the assessment of tumor vascular relationship in patients with pancreatic tumors in order to choose the proper treatment decision. Material and Methods: This study is a prospective study which was conducted in the Radiology Department of Man-soura University Hospital over the period from August 2016 to September 2019. This study included 79 patients, their ages ranged from 45 to 74 years old with mean age 58.3 years old. All patients were referred from oncology Center of Mansoura University and outpatient surgery clinics. The study was approved by our institution's ethics committee, and all patients gave their informed consent before inclusion in the study. CT scans were obtained with a MDCT scanner (Aquilion 64, Toshiba Medical Systems). CT protocols for pancreatic imaging vary at different institutions but typically include a multiphasic technique with a very thin section imaging and multiplanar reconstruction. Contrast enhanced images include: A late arterial or pancreatic phase and a portal or venous phase after injection of 100-120mL of intravenous non-ionic water soluble contrast material usually at rate of 4-5mL/sec. Results: This study included 79 patients, their ages ranged from 45 to 74 years old with mean age was 58.3 years. The most common affected site in the pancreas was the pancreatic head (47 lesions). All the lesions in our study were histopatho-logical proven malignant. The most common histopathological type in our study was pancreatic adenocarcinoma representing 61 lesions (77.21%). As regards the CT appearance of the pancreatic masses, most of the lesions were hypodense (71lesions). Detailed evaluation by CT angiography showed that the hepatic artery was involved in 35 cases, the SMA in 49 cases, the celiac trunk in 29 cases and the gartroduodenal artery in 47 cases. There was no arterial vascular involvement in 25 cases. Finally as regards the anatomical variations; accessory right hepatic artery was detected in 11 cases, Accessory left hepatic artery in 12 cases, replaced left hepatic artery in 14 cases, replaced right hepatic artery in 10 cases, replaced common hepatic artery in 9 cases and 23 cases showed no anatomical variants. Conclusion: Multidetector CT with CT angiography plays a major role in the diagnosis and staging of pancreatic carci-noma. The use of standardized technique and radiologic reporting method can improve the evaluation of the tumor-vessel relationship and precisely evaluate the arterial anatom-ical variants.

Background: This study designed to evaluate and compare surface physical and chemical characteristics of recently introduced rotary NiTi files Neolix (Neolix, Châtres-la-Foret, France), One Curve (Micro mega, France) and AF™ Blue S ONE File System (Fanta, USA) before and after 1st and 3rd use. Materials and Methods: In this study thirty brand-new endodontic files having tip size 25/0.6 of the following systems were used: Neolix (Neolix, Châtres-la-Foret, France), One Curve (Micro mega, France) and AF™ Blue S ONE One-File System (Fanta, USA). These files were equally divided into three groups (n=10). Ninety simulated curved canals (Endo Training Block-L; Dentsply Maillefer, Ballaigues, Switzerland) with curvature of 45o±10o, with 0.02taper, 0.15 mm apical diameter, and 16 mm length were used. File`s surfaces examined by Environmental Scanning Electron Microscope ESEM (FEI Quanta 250 FEG, Berlin, Germany) at 500X magnification before use. Cutting blade (active part) images been processed and their micrographs were analyzed at the tip, 2 and 4 mm short of its cutting tip. The Nickel (Ni) and Titanium (Ti) average contents (wt %) on the instrument`s surface were also analyzed before their use, using an Energy Dispersive Spectrometer Device (EDAX - AMETEK, Inc., Mahwah, NJ, USA). All instruments prepared using electric motor (Motor X-Smart Plus, Dentsply/Maillefer), following manufacturer`s instructions for each system. Each used file prepared three simulated canals, after each canal instrumentation, each file was removed for cleaning its flutes gently with sterile gauze, and for canal irrigation using with 2 mL/ 2.5% NaOCl irrigating solution. After the first and third instrumentation performed; files were cleaned, dried, stored and sent to SEM equipment for post-instrumentation files surface’s topography analysis and chemical composition of the NiTi content (wt %) according to the previously described pre-instrumentation analysis protocol. SEM micrographs recorded on a CD-ROM and projected for three blinded examiners’. They were given a spreadsheet including the instrument data (number, the location to be evaluated; tip, 0-2mm or 2-4mm from the tip) and the side of the instrument (detail facing up or down), and the criteria of defects and deformation assessment namely (irregular edges, grooves, micro-cavities and burrs).Data were recorded and statistically analyzed.Results: Analysis of surface defects (SEM) showed that; all file systems have pre-instrumentation surface defects which increased after use. Neolix file had highest significant difference in all detected surface defects with One Curve file, with AF™ Blue S ONE file in burs and micro-cavities at file`s Tip and 0-2mm, in all examination intervals(p

BackgroundMetformin has been used to treat type 2 Diabetes Mellitus since long time. It has two proposed anti-neoplastic mechanisms, direct (insulin-independent) and indirect (insulin-dependent) actions. PurposeTo assess the effect of Metformin on pathological response when combined with neoadjuvant chemotherapy in breast cancer. Material and MethodsA prospective study included stage II, III non-diabetic breast cancer patients who received neoadjuvant chemotherapy in our center during the period from May 2017 to March 2019. 59 patients met our inclusion criteria and completed the study, 27 patients received 850mg Metformin every 12 hrs with chemotherapy (group A), 32 patients received chemotherapy without Metformin (group B). Pathological response was assessed by Chevallier classification and residual cancer burden score (RCB). ResultsBoth groups were well balanced regarding base line characteristics. The results of our study showed that the rate of pathological complete response (pCR) was 14.8% in group (A) vs. 6.3% in group (B) with a P-value of 0.39. RCB class 3 was 40.7% in group (A) Vs. 68.8% in group (B) which was statistically significant with a (P-value of 0.031). Patients with triple-positive histology who had RCB class 3 were only (14.3%) in group (A) versus (60%) in group B. Patients with body mass index (BMI) ≥25 who had RCB 3 were 40% and 66.7% in group (A) and (B) respectively. ConclusionMetformin may increase the pCR especially in patients with BMI≥25 and patients with triple-positive histology, a larger phase III study is needed to confirm this finding.

Background: Breast cancer is one of the major causes of death among females, its early diagnosis allow better prognosis and prolonged survival rates of the patients. Post contrast dynamic MRI is the most sensitive method for breast cancer detection which has also good diagnostic performance for evaluation of different breast pathological lesions. Magnetic Resonance (MR) spectroscopy is a functional MRI technique which is used to study the metabolic profile of different breast lesions to improve the diagnostic accuracy of MRI especially in BIRADS 4 breast lesions in order to reduce the unnecessary biopsies.Aim of Study: Evaluation of the role of multi-voxel MR spectroscopy in the recategorization of BIRADS 4 breast lesions when combined with Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI).Material and Methods: This study included 63 patients, their ages ranged from 28 to 73 years old with mean age 46.7 years old. All the patients included in this study were subjected to history, clinical examination, MRI examination and his-topathology. Initially the included breast lesions were catego-rized as BIRADS 4 by conventional post contrast dynamic MRI techniques, and then we added the results of the magnetic resonance spectroscopic imaging to detect whether the spec-troscopic data can improve the diagnostic accuracy of the MRI study. Finally the reported diagnosis was confirmed by histopathological specimens obtained after excision biopsy and core needle biopsy. We used 1.5 T MRI system and the sequences performed included T1 & T2 pulse sequences, STIR and dynamic contrast enhanced MRI followed by MRS for the suspected lesions. For statistical analysis we used T-test and ROC curve.Results: This study included 63 female patients, their ages ranged from 28 to 73 years old with mean age 46.7 years old. All the breast lesion were categorized as BI-RADS 4 breast lesions based on the Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) then after magnetic resonance spectroscopy the breast lesions were re-categorized into BIRADS 3, 4 and 5 categories. Finally the results were compared to the histopathological results. The most common clinical presentation is palpable mass. We had 33 pathologically proven benign lesions and 30 pathologically proven malignant lesions. The diagnosis was downgraded into BIRADS 3 in 29 cases and upgraded into BIRADS 5 in 28 cases and in 6 cases there was no change in the BIRADS 4 categorization after MRS. During MRS examination the choline resonance peak was detected at a frequency of 3.23ppm, and the choline SNR was measured at cut off value of 2. There were statistically significant differences between malignant and benign breast lesions, the choline SNR measured 6.31±0.99 (mean ± SD) in the malignant lesions and it measured 1.902±0.47 (mean ± SD) in the benign lesions. The sensitivity, specificity, PPV, NPV and accuracy measured 81.3%, 62.6%, 76.5%, 67.1% and 73.4% for the DCE-MRI and measured 87.9%, 89.1%, 85.2%, 88.9% and 94.8% for combined assessment by MRS and DCE-MRI.Conclusion: Magnetic resonance spectroscopic imaging can be problem solving method for BIRADS 4 breast lesions when combined with dynamic contrast enhanced MRI to improve its diagnostic accuracy.

Background Regional nodal recurrence (RNR) in patients diagnosed with papillary thyroid carcinoma (PTC) has increased. Variable immunohistochemical (IHC) markers have been studied for predicting the likelihood of PTC for recurrence. We aimed to clarify the IHC expression of p53, Ecadherin and BRAF as potential markers of RNR in PTC. Method 145 (73 study group and 72 control group) patients with PTC were analyzed retrospectively between January 2010 and June 2017. Further classification to a specific histological variant was done, and IHC expression of p53, Ecadherin and BRAF was analyzed both in the primary tumor and in nodal recurrence. Results Regarding the risk of RNR, we found certain clinicopathologic features as elder age ≥55 years, tumor size >1 cm, presence of microscopic extrathyroid extension, presence of lymphovascular emboli, and conventional papillary subtype. Furthermore, IHC results for negative E-cadherin, and positive P53 and BRAF are significant risk factors, while radioactive iodine (RAI) adjuvant therapy decrease recurrence risk. Conclusion We found several risk factors for RNR in PTC diagnosed patients, all of which are easily achievable in clinical settings. In this regard, we suggested that patients with specific clinicopathologic and immunohistochemical features have strict follow up for early detection of RNR as it has a great impact on their survival.

Myopathy is a well-known adverse effect of statins, affecting a large sector of statins users. The reported experimental data emphasized on mechanistic study of statin myopathy on large muscles. Clinically, both large muscles and respiratory muscles are reported to be involved in the myotoxic profile of statins. However, the experimental data investigating the myopathic mechanism on respiratory muscles are still lacking. The present work aimed to study the effect of atorvastatin treatment on respiratory muscles using rat isolated hemidiaphragm in normoxic & hypoxic conditions. The contractile activity of isolated hemidiaphragm in rats treated with atorvastatin for 21 days was investigated using nerve stimulated technique. Muscle twitches, train of four and tetanic stimulation was measured in normoxic, hypoxic and reoxygenation conditions. Atorvastatin significantly increased the tetanic fade, a measure of muscle fatigability, in hypoxic conditions. Upon reoxygenation, rat hemidiaphragm regains its normal contractile profile. Co-treatment with coenzyme Q10 showed significant improvement in defective diaphragmatic contractility in hypoxic conditions. This work showed that atorvastatin treatment rapidly deteriorates diaphragmatic activity in low oxygen environment. The mitochondrial respiratory dysfunction is probably the mechanism behind such finding. This was supported by the improvement of muscle contractile activity following CoQ10 co-treatment.

Objective: Papillary thyroid carcinoma (PTC) is the most frequent histologic type of all thyroid malignancies. The presence of characteristic nuclear changes focally in a thyroid lesion may cause diagnostic dilemma. Immunohistochemistry may be helpful in the diagnosis of PTC yet not conclusive. The aim of this study is to test the applicability immunohistochemical markers; CK19, P63, CD56 and CD117 in distinguishing PTC from other follicular thyroid. Methods: Fifty nine cases of unequivocal diagnosis were selected to be rolled in our study; 24 papillary carcinoma cases and 35 cases representing other follicular throid lesions. Immunohistological studies include CK19, P63, CD56 and CD117. Subsequent statistical analysis of immunohistochemical data in relation to diagnosis was performed. Results: The diagnosis of PTC was significantly associated with Strong diffuse Ck19 expression, P63 expression and negative CD56 in relation to studied non PTC follicular thyroid lesions. On the other hand, CD117 was negative in most of the studied thyroid lesions with no significant difference between PTC and other lesions. CK19 was the most sensitive marker (91.2%) and P63 was the most specific one (87.5%), with better specificity in combining markers. Expression of CK19 and lost CD56 provided 97.1% sensitivity and 91.2% diagnostic accuracy in differentiating PTC from other studied lesions. Conclusions: Immunohistochemical markers, Ck19, P63 and CD56 are helpful in diagnosis of PTC and their combination can further improve diagnostic accuracy. CD117 is of no value in the diagnosis of studied cases.

Purpose To assess the role of 1H-magnetic resonance spectroscopy (1H-MRS) in the confirmation of pathological complete response after neoadjuvant chemotherapy in breast cancer. Material and methods Forty-seven cases (53.72 ± 8.53 years) were evaluated using magnetic resonance imaging (MRI) and 1H-MRS with choline (Cho) signal-to-noise ratio (SNR) measured followed by histopathology and ROC analyses. Results Twelve patients had complete response, and 35 patients had residual disease. Mean age was 53.72 ± 8.53 years. The mean tumour size before neoadjuvant chemotherapy (NAC) was 4.21 ± 0.99 cm and after NAC was 0.9 ± 0.44 cm.Positive total choline signal (tCho) was detected in all cases. The mean Cho SNR before NAC was 9.53 ± 1.7 and after NAC was 2.53 ± 1.3. The Cho SNR cut-off point differentiating between pathologic complete response (pCR) and the non pCR was 1.95. Dynamic MRI showed 83.3% sensitivity, 65.7% specificity, 45.5% positive predictive value, 92.0% negative predictive value, and 70.2% diagnostic accuracy. Combined evaluation done by using the dynamic MRI and 1H-MRS showed 91.5% diagnostic accuracy with 75.0% sensitivity, 97.1% specificity, 75% positive predictive value, and 91.9% negative predictive value. ROC curves of Cho SNR showed statistically significant differences between non pCR and pCR with AUC was 0.955, 82.9% sensitivity, 91.7% specificity, 96.7% positive predictive value, 64.7% negative predictive value, and 85.11% diagnostic accuracy. Conclusions 1H-MRS improves the diagnostic accuracy in the prediction of the pCR after NAC.

Background: The uterus has a complex lymphatic drainage consisting of many groups that are in danger of endometrial cancer (EC) spread. Lymph node metastasis is a genuine pointer of poor prognosis requiring adjuvant therapy. Lymphatic mapping surgically can be done by blue dye labeling and perioperative algorithm. Aim: To assess the role of perioperative sentinel lymph nodes (SLN) mapping algorithm in reducing the necessity of pelvic lymphadenectomy. Methods: Fifty patients with early stage I EC underwent surgical staging. Transcervical injection of methylene blue was used, laparotomy was done and retroperitoneal spaces were opened. All lymph nodes were histopathologically examined and the negative SLN were ultrastaged. Results: Methylene blue dye injection resulted in blue lymph nodes in 20 (40%) cases, suspicious in 2 (4%) and negative in 28 (56%). Histopathological examination of sampled lymph node showed metastases in 18/20 (90%) of blue nodes, 1/2 (50%) of suspicious nodes and 0/28 (0%) of negative nodes. There were no false negative cases in this study and the detection rate was 89%. Conclusion: Perioperative algorithm accuracy and simplicity make it a reliable approach for lymph node assessment in early stage EC.

Background and Aims Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy. Method This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody Results Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period. Conclusion we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.

Purpose: to demonstrate role of diffusion tensor imaging (DTI) in diagnosis of pediatric chronic kidney disease (CKD) using fraction anisotropy (FA) and apparent diffusion coefficient (ADC). Material and methods: Prospective study done on 35 CKD patients (19 boys, 16 girls; mean age 12.2±2.7 years) and 19 age and sex-matched volunteers. Patients with sclerotic (n = 25) and non-sclerotic (n= 10) CKD that underwent DTI of kidney. Results: Mean FA of renal cortex/ medulla in CKD (0.20±0.07, and 0.18±0.08) was significantly lower (p = 0.001) from volunteers (0.27±0.08, 0.31±0.09). Cutoff renal FA of cortex/ medulla used for diagnosis of CKD was 0.23, and 0.22 with AUC of 0.828, 0.828 and accuracy of 82.9%, 80.7%. Mean ADC of renal cortex/ medulla in CKD (1.98±0.23 and 2.03±0.23 X10-3mm2/s) was significantly higher (p = 0.001) that of volunteers (1.65±0.134 and 1.68±0.16 X10-3mm2/s. Cutoff renal ADC of cortex/medulla used to diagnosis of CKD were 1.75 and 1.85X10-3mm2/s with AUC of 0.828, 0.910, 0.828 and 0.81 and accuracy of 82.9%, 84.1%, 80.7% and 79.5%. FA of renal cortex/medulla in sclerotic CKD was significantly different (p = 0.001) than non-sclerotic CKD (0.26±0.07 and 0.25±0.08). The FA of renal cortex/medulla in CKD patients correlated with serum creatinine (r = -0.468; p = 0.000, r =-0.381; p = 0.001), e GFR (r = 0.364; p = 0.002, r = 0.318; p = 0.007). Conclusion: FA and ADC of renal cortex/ medulla can help in diagnosis of CKD, FA cortex/ medulla predicts sclerotic CKD and correlated with some of serum biomarkers.

Guillain-Barre syndrome (GBS) represents the most common cause of acute flaccid paralysis and is characterized by muscle weakness frequently accompanied by respiratory and bulbar paralysis which oftentimes can be life-threatening. Early recognition and intervention are essential to prevent potential complications and help hasten recovery. Herein, we report a case of a middle-aged female who presented with nonspecific gastrointestinal symptoms that were shortly followed by a unique combination of new-onset facial diplegia and asymmetric lower extremity areflexia. Treatment with intravenous immunoglobulins (IVIG) was initiated following a prompt diagnosis of GBS was made. Clinicians should always be vigilant about the possibility of GBS in the appropriate clinical setting and be aware of the essentials of management of this potentially treatable disease.

Background and Aims Glomerular diseases (GDs) impose a substantial burden on patients and health care systems, and they are considered a major cause of end-stage renal disease (ESRD) worldwide. Morbidity and mortality have shown to be substantially higher in patients with GDs than in the general population. In Egypt, there is yet no available national registry for GDs, and GDs outcome is not adequately studied. Therefore, it is of considerable interest to study patterns and outcomes of GDs in our locality. Method Patients with features suggesting GDs presenting to Mansoura nephrology and dialysis unit (MNDU) were recruited in this study between 1 July 2017 and 30 June 2018, and those with biopsy-proven GDs were prospectively followed up for a minimum of 6 months or until either death or reaching ESRD. ESRD was defined as initiation of long-term dialysis or eGFR persistently Results Sixty-six patients (21 males and 45 females) with biopsy-proven GDs were included and completed the required period of follow up. The median age of the studied patients was 32 years (IQR 23 - 46.45). Fifty percent of the cases had hypertension and only one patient had was diabetic. The main indications for renal biopsy were unexplained kidney function decline (62%) followed by subnephrotic (23%) and nephrotic presentation (15%). Diffuse proliferative GN followed by MPGN and sclerosing GN were the most frequently encountered histopathological patterns. Primary and secondary GDs constituted 30.3% and 69.7% respectively. Lupus nephritis (LN) was the most common cause of secondary GDs and class IV LN was the most frequently encountered class accounting for 16 cases (51.6%) of patients with lupus. By the end of 6-month follow up, renal recovery was achieved in 30 patients (45.5%), 21 patients (31.8%) progressed to ESRD and 7 patients (10.6%) had died. Urban residency and total renal chronicity score were the most significant predictors of renal recovery. Conclusion Diffuse proliferative GN is the most common histopathological pattern, and secondary GDs, particularly those related to lupus, are more frequently encountered than primary GDs in our center. Unfortunately, quick complete recovery is not the rule and is possibly predictable by less chronic changes in biopsy.

Background Lung cancer has a very poor prognosis and high mortality. Positive sputum for malignant and/or atypical cells warrants the need for fibreoptic bronchoscopy. White light bronchoscopy (WLB) is usually unable to detect preinvasive lesions; therefore, autofluorescence bronchoscopy (AFB) was introduced as a gold standard for detecting such lesions. The aim of this work was to investigate the role of I-scan as a screening tool for cancer in smoker patients showing positive sputum cytology. Results New suspicious findings under I-scan occurred in 11 patients (36.7%). The overall sensitivity of WLB alone to diagnose malignancy is 23.3%, in contrast to an added sensitivity of 50% when I-scan was combined with white light (p value < 0.05). The specificity of I-scan could not be assessed in the absence of control cases (true negatives). No major complications or deaths occurred. Haemorrhage and bronchospasm were the commonest minor complications. Conclusions The addition of I-scan to the routine white light examination can increase the overall sensitivity of bronchoscopic screening in cases of sputum suspicious for malignancy if put in experienced hand. The suggested increase in procedure duration due to the combined use of I-scan and white light bronchoscopy is not associated with life-threatening complications.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we identified that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool sensory stimuli, while autonomic thermoregulatory function is active. This neonatal deficit was mimicked in control neonates by chemogenetic inactivation of oxytocin neurons. Importantly, intranasal administration of oxytocin was able to rescue the phenotype and brain Erk signaling impairment in mutants. This preclinical study establishes for the first-time early life impairments in thermosensory integration and shows the therapeutic potential benefits of intranasal oxytocin treatment on neonatal atypical sensory reactivity.

BackgroundTumor recurrence and progression are two important landmarks in non-muscle-invasive bladder cancer (NMIBC) patients. Periodic cystoscopic follow-up visits of NMIBC patients are necessary after complete tumor resection as tumor recurrence occurs in nearly 70–80% of cases. Patients with a hi

Myopathy is the most commonly reported adverse effect of statins. All statins are associated with myopathy, though with different rates. Rosuvastatin is a potent statin reported to induce myopathy comparable to earlier statins. However, in clinical practice most patients could tolerate rosuvastatin over other statins. This study aimed to evaluate the myopathic pattern of rosuvastatin in rats using biochemical, functional and histopathological examinations. The possible deleterious effects of rosuvastatin on muscle mitochondria were also examined. The obtained results were compared to myopathy induced by atorvastatin in equimolar dose. Results showed that rosuvastatin induced a rise in CK, a slight increase in myoglobin level together with mild muscle necrosis. Motor activity, assessed by rotarod, showed that rosuvastatin decreased rats' performance. All these manifestations were obviously mild compared to the prominent effects of atorvastatin. Parallel results were obtained in mitochondrial dysfunction parameters. Rosuvastatin only induced a slight increase in LDH and a minor decrease in ATP (∼14%) and pAkt (∼12%). On the other hand, atorvastatin induced an increase in LDH, lactate/pyruvate ratio and a pronounced decline in ATP (∼80%) and pAkt (∼65%). These findings showed that rosuvastatin was associated with mild myotoxic effects in rats, especially when compared to atorvastatin.

INTRODUCTION: Nanotechnology is the technology of diagnosing, treating, and preventing diseases using nanoscale structured materials. Zinc oxide nanoparticles (ZnO NPs) have useful effects for their less environmental hazards and for their application usages: tooth pastes, biomedicine and food as zinc supplements. On the other hand, ZnO NPs have toxic effect due to their tissue accumulation ability. Quercetin (Qc) is an antioxidant, categorized as a flavonol. Its beneficial effects are attributed to its phenolic hydroxyl groups. It has antioxidant and antiinflammatory activities. OBJECTIVES: To evaluate the effect of ZnO NPs on rat parotid salivary glands and to investigate the possible protective role of Qc. MATERIALS AND METHODS: Twenty-four adult male albino rats were divided into three equal groups: group (I) control, group (II) received ZnO NPs 300 mg/kg and group (III) received ZnO NPs 300 mg/kg + Qc 200 mg/kg for 28 days. At the end of the experiment, animals were euthanized and the parotid glands were dissected out. The effect of ZnO NPs on the parotid glands as well as the protective role of Qc were assessed by transmission electron microscopy. RESULTS: In group(II) the acinar cells showed signs of toxicity as apoptotic nuclei, degenerated mitochondria, dilated rough endoplasmic reticulum and vacuolization in the cytoplasm. Group (III) parotid glands exhibited remarkable improvement in the ultrastructure of their acinar cells and duct system. This appearance was near to that of control group. CONCLUSIONS: The study proved ZnO NPs toxicity and revealed that oral administration of Qc effectively prevented the toxicity associated with ZnO NPs administration in rat models. Thus, Qc might be used as a prophylactic treatment to prevent ZnO NPs toxicity.

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Purpose To assess the role of 1H-magnetic resonance spectroscopy (1H-MRS) in the confirmation of pathological complete response after neoadjuvant chemotherapy in breast cancer. Material and methods Forty-seven cases (53.72 ± 8.53 years) were evaluated using magnetic resonance imaging (MRI) and 1H-MRS with choline (Cho) signal-to-noise ratio (SNR) measured followed by histopathology and ROC analyses. Results Twelve patients had complete response, and 35 patients had residual disease. Mean age was 53.72 ± 8.53 years. The mean tumour size before neoadjuvant chemotherapy (NAC) was 4.21 ± 0.99 cm and after NAC was 0.9 ± 0.44 cm.Positive total choline signal (tCho) was detected in all cases. The mean Cho SNR before NAC was 9.53 ± 1.7 and after NAC was 2.53 ± 1.3. The Cho SNR cut-off point differentiating between pathologic complete response (pCR) and the non pCR was 1.95. Dynamic MRI showed 83.3% sensitivity, 65.7% specificity, 45.5% positive predictive value, 92.0% negative predictive value, and 70.2% diagnostic accuracy. Combined evaluation done by using the dynamic MRI and 1H-MRS showed 91.5% diagnostic accuracy with 75.0% sensitivity, 97.1% specificity, 75% positive predictive value, and 91.9% negative predictive value. ROC curves of Cho SNR showed statistically significant differences between non pCR and pCR with AUC was 0.955, 82.9% sensitivity, 91.7% specificity, 96.7% positive predictive value, 64.7% negative predictive value, and 85.11% diagnostic accuracy. Conclusions 1H-MRS improves the diagnostic accuracy in the prediction of the pCR after NAC.

International audience; Vascular calcification (VC) is the pathological accumulation of calcium phosphate crystals in one of the layers of blood vessels, leading to loss of elasticity and causing severe calcification in vessels. Medial calcification is mostly seen in patients with chronic kidney disease (CKD) and diabetes. Identification of key enzymes and their actions during calcification will contribute to understand the onset of pathological calcification. Phospholipase D (PLD1, PLD2) is active at the earlier steps of mineralization in osteoblasts and chondrocytes. In this study, we aimed to determine their effects during high-phosphate treatment in mouse vascular smooth muscle cell line MOVAS, in the ex vivo model of the rat aorta, and in the in vivo model of adenine-induced CKD. We observed an early increase in PLD1 gene and protein expression along with the increase in the PLD activity in vascular muscle cell line, during calcification induced by ascorbic acid and beta-glycerophosphate. Inhibition of PLD1 by the selective inhibitor VU0155069, or the pan-PLD inhibitor, halopemide, prevented calcification. The mechanism of PLD activation is likely to be protein kinase C (PKC)-independent since bisindolylmaleimide X hydrochloride, a pan-PKC inhibitor, did not affect the PLD activity. In agreement, we found an increase in Pld1 gene expression and PLD activity in aortic explant cultures treated with high phosphate, whereas PLD inhibition by halopemide decreased calcification. Finally, an increase in both Pld1 and Pld2 expression occurred simultaneously with the appearance of VC in a rat model of CKD. Thus, PLD, especially PLD1, promotes VC in the context of CKD and could be an important target for preventing onset or progression of VC.

Background Acne vulgaris is a multifactorial disorder of the pilosebaceous units. Several studies have reported that insulin-like growth factor (IGF)-1, forkhead box transcription factor (Fox)O1 and mammalian target of rapamycin (mTOR) interactions may be the key to understanding the links between genetic and environmental factors in acne vulgaris. Objectives To evaluate the immunohistochemical detection of mTOR and FoxO1 in the skin, and the serum level of IGF-1 in patients with acne vulgaris. Methods This study was carried out on 60 participants, including 40 patients with acne and 20 controls. A diet questionnaire was administered to the patients and controls. Serum levels of IGF-1 were measured using enzyme-linked immunosorbent assay, and skin biopsies were taken from lesions on the backs of the patients and controls. FoxO1 and mTOR expression was detected using immunohistochemistry. Results A significantly higher serum IGF-1 level was found in the patients with acne than in the controls. The cytoplasmic expression of FoxO1 was found to be significantly greater in the acne group, whereas in the control subjects this expression was likely to be nuclear. Both the cytoplasmic expression and the nuclear expression of mTOR were significantly more intense in the patients with acne than in the controls. Excess consumption of a high-glycaemic-load diet was significantly associated with higher serum levels of IGF-1 and cytoplasmic expression of FoxO1 and mTOR. Conclusions These results suggest that FoxO1, mTOR, serum IGF-1 and a high-glycaemic-load diet may play a role in acne pathogenesis.

Mammalian phospholipase D (PLD) mostly hydrolyzes phosphatidylcholine producing phosphatidic acid. PLD activity was previously detected in different osteoblastic cell models, and was increased by several growth factors involved in bone homeostasis. To confirm possible actions of PLD isoforms during mineralization process, we analyzed their effects in osteoblastic cell models and during bone formation. PLD1 expression, along with PLD activity, increased during differentiation of primary osteoblasts and Saos-2 cells, and peaked at the onset of mineralization. Subsequently, both PLD1 expression and PLD activity decreased, suggesting that PLD1 function is regulated during osteoblast maturation. In contrast, PLD2 expression was not significantly affected during differentiation of osteoblasts. Overexpression of PLD1 in Saos-2 cells improved their mineralization potential. PLD inhibitor Halopemide or PLD1-selective inhibitor, led to a decrease in mineralization in both cell types. On the contrary, the selective inhibitor of PLD2, did not affect the mineralization process. Moreover, primary osteoblasts isolated from PLD1 knockout (KO) mice were significantly less efficient in mineralization as compared with those isolated from wild type (WT) or PLD2 KO mice. In contrast, bone formation, as monitored by high-resolution microcomputed tomography analysis, was not impaired in PLD1 KO nor in PLD2 KO mice, indicating that the lack of PLD1 or that of PLD2 did not affect the bone structure in adult mice. Taken together, our findings indicate that PLD activity, especially which of PLD1 isoform, may enhance the mineralization process in osteoblastic cells. Nonetheless, the lack of PLD1 or PLD2 do not seem to significantly affect bone formation in adult mice.