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Food poisoning risk related to the consumption of contaminated food with known foodborne pathogens or antibiotic-resistant bacteria is currently a serious threat for public health. Thus, pathogenic methicillin-resistant Staphylococcus strains are considered as one of the major cause of foodborne diseases in hospitals. The present study aims to determine the prevalence and the antibiotic resistance patterns of Staphylococcus in various types of hospital food samples, work surfaces and its carriage by food handlers. A total of 608 collected samples including 300 food samples, 238 food contact surfaces and 70 nasal and hand samples were tested. The identified Staphylococcus and their antibiotic resistance patterns were analysed using the agar disk-diffusion and PCR method was used for mecA resistance gene amplification. The prevalence of S. aureus and the coagulase-negative staphylococci were 17·33 and 23·33%, respectively. The antibiotic resistance reached 100% towards oxacillin and Penicillin G for both S. aureus and CoNs. The mecA gene was detected in 5·71% (4/70) and 7·69% (4/52) of S. aureus and CoNs strains, respectively. The outcome of this study enlightens isolation of MRSA strains and resistant CoNs from food, food contact surfaces and food handlers. The presence of this resistant species in this critical setting, where products were intended to vulnerable and immunocompromised patients, represents a serious threat to this community. It can be a source of nosocomial infection and more precautions must be taken to prevent staphylococci food contamination mainly in hospitals. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study describing the antibiotic resistance patterns of Staphylococcus aureus and coagulase-negative Staphylococcus isolated from hospital food, food contact surfaces and food handlers samples in a Moroccan hospital kitchen. High levels of multi-resistance were reported. The alarming outcome of this study emphasizes the crucial need of implementing an approach to fight multidrug-resistant staphylococci mainly in healthcare settings, where the community have already compromised health issues., (© 2020 The Society for Applied Microbiology.)

Background: Artificial intelligence (AI) is increasingly applied in the field of breast imaging., Objectives: What are the main areas where AI is applied in breast imaging and what AI and computer-aided diagnosis (CAD) systems are already available?, Materials and Methods: Basic literature and vendor-supplied information are screened for relevant information, which is then pooled, structured and discussed from the perspective of breast imaging., Results: Original CAD systems in mammography date almost 25 years back. They are much more widely applied in the United States than in Europe. The initial CAD systems exhibited limited diagnostic abilities and disproportionally high rates of false positive results. Since 2012, deep learning mechanisms have been applied and expand the application possibilities of AI., Conclusion: To date there is no algorithm that has beyond doubt been proven to outperform double reporting by two certified breast radiologists. AI could, however, in the foreseeable future, take over the following tasks: preselection of abnormal examinations to substantially reduce workload of the radiologists by either excluding normal findings from human review or by replacing the double reader in screening. Furthermore, the establishment of radio-patho-genomic correlations and their translation into clinical practice is hardly conceivable without AI.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected ( P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose ( r = -0.40; P = .01) but not for GP T1 times ( r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.

Background and Objectives: Food in healthcare settings are complementary to medical treatment, hence it should be produced in good sanitary conditions. In fact, hospitalized and immune-compromised patients are more likely to have foodborne infections than the rest of the community. The aim of our study is to evaluate the microbiological quality of food contact surfaces in a hospital kitchen in Morocco., Materials and Methods: A total of 238 samples was collected from kitchen surfaces and analyzed for total aerobic mesophilic bacteria (AMC), Enterobacteriaceae and Staphylococcus aureus count and the presence of Salmonella spp., Pseudomonas spp. and Listeria monocytogenes., Results: The bacteriological analysis shows that the highest rates of compliance with good hygienic conditions were obtained in baking worktops (77%) and serving meal worktops (50%) and the vegetables cutting boards (45.83%). In contrary, some surfaces show a low level of compliance, such as the raw meat cutting boards (96%). The isolated bacteria were S. aureus , coagulase-negative staphylococci, Escherichia coli , Serratia marcescens , Serratia odorifera , Raoultela ornithiaolytica and Pseudomonas aeroguinosa ., Conclusion: The actual results indicate that the high levels of bacterial counts on kitchen surfaces, presents an evident need to improve the hygienic process and adopt an HACCP system in this facility., (Copyright© 2019 Iranian Neuroscience Society.)

Purpose: To develop a novel magnetic resonance imaging (MRI) approach for the noninvasive assessment of hypoxia and neovascularization in breast tumors., Procedures: In this IRB-approved prospective study, 20 patients with suspicious breast lesions (BI-RADS 4/5) underwent multiparametric breast MRI including quantitative BOLD (qBOLD) and vascular architecture mapping (VAM). Custom-made in-house MatLab software was used for qBOLD and VAM data postprocessing and calculation of quantitative MRI biomarker maps of oxygen extraction fraction (OEF), metabolic rate of oxygen (MRO 2 ), and mitochondrial oxygen tension (mitoPO 2 ) to measure tissue hypoxia and neovascularization including vascular architecture including microvessel radius (VSI), density (MVD), and type (MTI). Histopathology was used as standard of reference. Appropriate statistics were performed to assess and compare correlations between MRI biomarkers for hypoxia and neovascularization., Results: qBOLD and VAM data with good quality were obtained from all patients with 13 invasive ductal carcinoma (IDC) and 7 benign breast tumors with a lesion diameter of at least 10 mm in all spatial directions. MRI biomarker maps of oxygen metabolism and neovascularization demonstrated intratumoral spatial heterogeneity with a broad range of biomarker values. Bulk tumor neovasculature consisted of draining venous microvasculature with slow flowing blood. High OEF and low mitoPO 2 were associated with low MVD and vice versa. The heterogeneous pattern of MRO 2 values showed spatial congruence with VSI. IDCs showed significantly higher MRO 2 (P = 0.007), lower mitoPO 2 (P = 0.021), higher MVD (P = 0.005), and lower (i.e., more pathologic) MTI (P = 0.001) compared with benign breast tumors. These results indicate that IDCs consume more oxygen and are more hypoxic and neovascularized than benign tumors., Conclusions: We developed a novel MRI approach for the noninvasive assessment of hypoxia and neovascularization in benign and malignant breast tumors that can be easily integrated in a diagnostic MRI protocol and provides insight into intratumoral heterogeneity.

Human papillomavirus (HPV) persistent infection is the necessary but not sufficient cause of cervical cancer. Other co-factors are required to induce cell transformation that will evolve to malignant cervical cancer. These co-factors include physical elements, other sexually transmitted infections, and immune response. Chlamydia trachomatis the most common bacterial sexually transmitted infection is often asymptomatic but causes various syndromes such as cervicitis, endometritis, pelvic inflammatory disease, and infertility. It is established that this bacterium is involved in cell proliferation process and inhibit apoptosis. Furthermore, C. trachomatis may induce chronic inflammation, interfere with immune response by decreasing the number of antigen presenting cells, and reduce the cell-mediated immunity allowing the persistence of HPV. However, it is unclear whether this bacterium plays a particular role in cervical cancer induction. We therefore aimed at enlightening the actual knowledge about the relationship between C. trachomatis and cervical cancer or precursor lesions through a systematic literature review. We summarized and analyzed the epidemiological data on C. trachomatis and its co-infection with HPV and their association to cervical cancer.

Background: The pathogenicity of cagA-positive H. pylori strains is associated with the number and type of repeated sequences named EPIYA located in the C-terminal region of the CagA protein. The aim of this study is to determine the polymorphism of the H. pylori cagA 3' region circulating in Morocco and its association with different gastric pathologies., Methods: A total of 1353 consenting patients, were recruited in this study. The gastric biopsies performed during endoscopy were used for histological examination and for molecular characterization of H. pylori. The study of the type and number of "EPIYA" motif was identified by PCR directly on H. pylori positive biopsies., Results: Of all the biopsies, the infection rate was 61.1%. The cagA gene was amplified in 68.9% of the cases and the analysis of the 3' region of cagA showed the exclusive presence of the "Western CagA" type with a predominance of the EPIYA-ABC motif (71.4%). The number of EPIYA-C motif varies from 0 to 2. The multinomial analysis shows that the infection with strains of H. pylori having two EPIYA-C motifs is a factor that increases the risk of developing gastric cancer compared to gastritis cases with strains lacking this motif (OR = 11.64; CI: 3.34-45.15), whereas this risk is 6 fold higher in comparison with duodenal ulcer cases (OR = 6, CI: 1.29-27.76)., Conclusions: The results of this study suggest that the number of EPIYA-C motifs might be useful as a predictive marker of the infection evolution and will help in the identification of patients at high risk of developing gastric cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To identify the prevalence and the types of Neisseria gonorrhoeae (NG) resistance plasmids-mediated penicillin (PPNG) and tetracycline (TRNG), the ciprofloxacin resistance (CRNG), and related risk factors of each types of resistance., Methods: The beta-lactamase-producing plasmid types (Africa, Asia, and Toronto), tetM tetracycline resistance plasmid types (America and Dutch), and the determination of the Ser-91 mutation of GyrA were detected by specifics PCRs on 149 diagnosed NG positives samples followed by Hinf1 digestion for tetM and gyrA mutation., Results: 135 (90.1%) samples showed a profile of molecular resistance to at least one antibiotic with predominance of ciprofloxacin resistance. In fact, 36 (24.2%) and 69 (46.3%) cases harbored PPNG and TRNG, respectively, and 116 (77.9%) cases showed the mutation Ser-91 of GyrA (CRNG). From a total of 36 PPNG isolates, the Toronto, Asian, and Toronto/Asian types were detected in 13 (36.1%), 10 (27.8%), and 13 (36.1%) cases, respectively, whereas the African type was not detected. In addition, the American type of TRNG was detected in 92.8% (64/69) of cases, while the Dutch type was detected in 7.2% (5/69) of cases. The association of demographics and clinical variables with NG resistance to ciprofloxacin, penicillin, and tetracycline was studied and the risk factors have been determined., Conclusion: Resistance to penicillin, tetracycline, and ciprofloxacin among NG samples positives remained at high levels in Morocco as determined by molecular profile. So, the use of molecular tools for NG antimicrobial resistance detection can help in the management and spread limitation of this infection.

The complex architecture of bone has been investigated for several decades. Some pioneer works proved an existing link between microstructure and external mechanical loading applied on bone. Due to sinuous network of canals and limitations of experimental acquisition technique, there has been little quantitative analysis of three-dimensional description of cortical network. The aim of this study is to provide an algorithmic process, using Python 3.5, in order to identify 3D geometrical characteristics of voids considered as canals. This script is based on micro-computed tomographic slices of two bone samples harvested from the humerus and femur of male cadaveric subject. Slice images are obtained from 2.94 μm isotropic resolution. This study provides a generic method of image processing which considers beam hardening artefact so as to avoid heuristic choice of global threshold value. The novelty of this work is the quantification of numerous three-dimensional canals features, such as orientation or canal length, but also connectivity features, such as opening angle, and the accurate definition of canals as voids which ranges from connectivity to possibly another intersection. The script was applied to one humeral and one femoral samples in order to analyse the difference in architecture between bearing and non-bearing cortical bones. This preliminary study reveals that the femoral specimen is more porous than the humeral one whereas the canal network is denser and more connected., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this study is to investigate in vitro antioxidant and antibacterial activities of the aqueous and hydroethanolic extracts for aerial parts of Herniaria hirsuta . Extracts were screened for their possible antioxidant activities by three tests: DPPH free radical-scavenging, reducing power, and molybdenum systems. The screening of antibacterial activity of extracts was individually evaluated against sixteen bacteria species using a disc diffusion method. Flavonoids, total phenols, and tannins content were performed for both extracts. It shows higher content in the hydroethanolic extract. The hydroethanolic extract showed a significant antioxidant activity for the three methods studies to the aqueous extract, but nonsignificant results compared to the reference (BHT). However, both extracts have negative effect on the strains studies for the antibacterial activity.

Introduction: Lynch syndrome (LS) is an autosomal dominant disorder characterized by early age of onset and increased risk of developing extracolonic tumors. Molecular diagnosis of LS requires identification of germline mutations in one of the Mismatch Repair (MMR) genes., Aim: The objective of the study was to investigate the prevalence of MLH1/MSH2 mutation carriers among Moroccan patients with colorectal cancer (CRC) in a hospital-based cohort., Methods: In this study, 214 CRC patients from COLORECFez cohort were included. Patients whose tumors showed MMR deficiency (MMR-D) and wild-type BRAF were selected to undergo mutational analysis of the MLH1 and MSH2 genes using Sanger sequencing., Results: A total of 24 MMR-D tumors were identified (11.2%) among 214 CRC tested for MMR protein expression. The BRAF p.Val600Glu mutation was absent in all tumors deficient for MLH1 protein. Molecular screening showed germline MMR mutations (MLH1/MSH2) in four cases, two of which fulfilled Amsterdam criteria II and two met at least one of the revised Bethesda guidelines. The estimated frequency of MLH1/MSH2 mutations in Moroccan CRC patients was 1.87%., Conclusions: The present study reports a relatively high incidence of MLH1/MSH2 (1.87%). These results confirm the contribution of MMR genes to CRC susceptibility in our population and provide evidence regarding the requirement of implementing a national screening program for LS in Morocco.

Background: This systematic review was conducted to explain the association between dairy products and colorectal cancer (CRC) risk in Middle Eastern and North African countries (MENA)., Methods: The database consulted were PubMed, Clinical Trials, and Cochrane to extract the relevant studies published till the 31stof December 2016, using inclusion and exclusion criteria according to Prisma Protocol. The characteristics of these studies comprised the consumption of all types of dairy products in relation to CRC risk., Results: Seven studies were included in this review. For dairy products overall, no significant association was found. Regarding modern dairy products, included studies found controversial results with OR = 9.88 (95% CI: 3.80-24.65) and OR a  = 0.14 (95% CI: 0.02-0.71). A positive association was reported between traditional dairy products and CRC risk, to OR = 18.66 (95% CI: 3.06-113.86) to OR = 24 (95% CI: 1.74-330.82) to ORa = 1.42 (95% CI: 0.62-3.25), p trend  = 0.03. Calcium was inversely associated with the CRC risk with OR a  = 0.08 (95% CI: 0.04-0.17)., Conclusion: This is the first systematic review which illustrated the association between dairy consumption and CRC risk in MENA region. The results were inconsistent and not always homogeneous. Further specified studies may be warranted to address the questions about the association between CRC and dairy products in a specific context of MENA region.

Digital ulcers generally arise in a context of microangiopathy-related focal ischemia. In women, connective tissue diseases are the main etiology, while in men the cause is often diffuse arterial disease, e.g. Leo-Buerger disease, or emboligenic heart disease. A paraneoplastic origin of digital necrosis due to ischemia is rarely reported. A 75-year-old man presented with cyanosis of the fingertips and toes that had begun one month earlier. The physical examination found pulp ulcers on the fingers and toes of both hands and feet. Two weeks later, necrotic damage developed distally, with no other associated symptoms. Blood tests were suggestive of Kahler disease; immunodeficiency disorders tests were negative; the cyroglobulin test was positive. Multiple-drug chemotherapy was followed by clinical improvement. Distal necrotic damage is a frequent inaugural symptom in vascular disease. If the common causal mechanisms (iatrogenic, occupational, toxic, atheromatous, emboligenic heart disease, or systemic disease) have been ruled out, it is important to search for a blood disorder or cancer as the cause of distal necrotic damage., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: Microcalcifications are a common finding in mammography and usually require invasive procedures to diagnose or exclude malignancy. As many microcalcifications are due to benign lesions, we wanted to assess whether breast MRI as an additional diagnostic tool may be used to distinguish benign from malignant in this setting., Materials and Methods: Eligible for this retrospective, IRB-approved observational study were 858 consecutive patients (mean age 54±11years) undergoing stereotactically-guided biopsies of suspicious mammographic microcalcifications during three year at our institution. Finally included were 152 patients who also underwent breast MRI <8weeks prior to biopsy. In case of malignant or lesions of uncertain malignant potential, subsequent surgery was performed. Benign findings were confirmed by imaging follow-up. BI-RADS category assignments from the original mammography and breast MRI reports were compared to the final diagnosis (benign vs. malignant) to determine diagnostic benchmarks., Results: Histopathology revealed 81 benign (53.3%), 41 DCIS (27%) and 30 (19.7%) invasive cancers. Sensitivity, specificity, positive and negative predictive values for breast MRI were 97.2% (69/71), 39.5% (32/81), 58.5% (69/118) and 94.1% (32/34), respectively. Thus, 32/81 unnecessary biopsies in benign lesions (39.5%) may have been avoided, missing 2/71 malignant lesions (2.8%), both DCIS G2., Conclusion: Breast MRI as an additional diagnostic tool can be used to accurately distinguish benign from malignant mammographic microcalcifications and may thus be helpful to reduce unnecessary breast biopsies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Assess the performance of breast MRI to diagnose breast cancer in BI-RADS 4 microcalcifications detected by mammography., Materials and Methods: This retrospective, IRB-approved study included 248 consecutive contrast-enhanced breast MRI (1.5T, protocol in accordance with EUSOBI recommendations) performed to further diagnose BI-RADS 4 microcalcifications detected at mammography during a 3-year period. Standard of reference had to be established by histopathology. Routine consensus reading results by two radiologists were dichotomized as positive or negative and compared with the reference standard (benign vs malignant) to calculate diagnostic parameters., Results: There were 107 malignant and 141 benign microcalcifications. Malignancy rates were 18.3% (23/126 BI-RADS 4a), 41.7% (25/60 BI-RADS 4b) and 95% (59/62 BI-RADS 4c). There were 103 true-positive, 116 true-negative, 25 false-positive, and 4 false-negative (one invasive cancer, three DCIS; 2 BI-RADS 4c, 1 BI-RADS 4b on mammography) breast MRI findings, effecting a sensitivity, specificity, PPV, and NPV of 96.3% (95%-CI 90.7-99.0%), 82.3% (95%-CI 75.0-88.2%), 80.5% (95%-CI 72.5-87.0%) and 96.7% (95%-CI 91.7-99.1%), respectively., Conclusion: MRI is an accurate tool to further diagnose BI-RADS 4a and 4b microcalcifications and may be helpful to avoid unnecessary biopsies in BI-RADS 4a and 4b lesions. BI-RADS 4c microcalcifications should be biopsied irrespective of MRI findings.

Background: We aimed to investigate an automated semi-quantitative software as an imaging biomarker for the prediction of tissue response (TR) after completion of neoadjuvant chemotherapy (NAC)., Methods: Breast magnetic resonance imaging (MRI) (1.5T, protocol according to international recommendations) of 67 patients with biopsy-proven invasive breast cancer were examined before and after NAC. After completion of NAC, histopathologic assessments of TR were classified according to the Chevallier grading system (CG1/4: full/non-responder; CG2/C3: partial responder). A commercially available fully automatic software (CADstream) extracted MRI parameters of tumor extension (tumor diameter/volume: TD/TV). Pre- versus post-NAC values were compared (ΔTV and ΔTD). Additionally, the software performed volumetric analyses of vascularization (VAV) after NAC. Accuracy of MRI parameters to predict TR were identified (cross-tabs, ROC, AUC, Kruskal-Wallis)., Results: There were 37 (34.3%) CG1, 7 (6.5%) CG2, 53 (49.1%) CG3, and 11 (10.2%) CG4 lesions. The software reached area under the curve levels of 79.5% (CG1/complete response: ΔTD), 68.6% (CG2, CG3/partial response: VAV), and 88.8% to predict TR (CG4/non-response: ΔTV)., Conclusion: Semi-quantitative automated analysis of breast MRI data enabled the prediction of tissue response to NAC.

Purpose To assess the use of magnetic resonance (MR) imaging for diagnosis of malignancy in lesions that manifest as microcalcifications at mammography. Materials and Methods Two independent readers performed a systematic review of the literature published as of February 1, 2016, by using predefined search terms. All studies in which contrast material-enhanced MR imaging was used for assessment of mammographic microcalcifications that were assigned Breast Imaging Reporting and Data System (BI-RADS) scores of 3-5 were deemed eligible. The standard of reference was established at clinical follow-up examination or histopathologic evaluation. Study design, technical parameters, number of true- and false-positive and true- and false-negative results were extracted to fit a cross-tabulation. Quality Assessment of Diagnostic Accuracy Studies-2 applet was used to probe for bias. Statistical analysis included data pooling, meta-regression, heterogeneity testing, and forest plot construction. Results Twenty studies met the inclusion criteria. These comprised 1843 lesions with a mean prevalence of malignancy of 40.6%. Bivariate analysis revealed pooled sensitivity and specificity of 87% (95% confidence interval [CI]: 81%, 92%) and 81% (95% CI: 75%, 86%) for all lesions, respectively; 95% (95% CI: 91%, 98%) and 61% (95% CI: 52%, 69%) for invasive lesions only, respectively; 57% (95% CI: 59%, 81%) and 32% (95% CI: 15%, 92%) for BI-RADS 3 lesions, respectively; 92% (95% CI: 85%, 96%) and 82% (95% CI: 74%, 88%) for BI-RADS 4 lesions, respectively; and 95% (95% CI: 87%, 99%) and 66% (95% CI: 26%, 92%) for BI-RADS 5 lesions. Diagnostic criteria other than presence of enhancement were inversely associated with sensitivity (P ≤ .013). Conclusion Breast MR imaging is not recommended for diagnosis of malignancy in BI-RADS 3 and 5 mammographic microcalcifications, but can be considered for BI-RADS 4 mammographic microcalcifications. The presence or absence of enhancement is the preferable diagnostic criterion to rule out malignancy in mammographic microcalcifications at breast MR imaging. © RSNA, 2016 Online supplemental material is available for this article.

Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08-173.73] and 9.17 [2.06-40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02-0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate the performance of MRI for diagnosis of breast cancer in non-calcified equivocal breast findings., Materials and Methods: We performed a systematic review and meta-analysis of peer-reviewed studies in PubMed from 01/01/1986 until 06/15/2015. Eligible were studies applying dynamic contrast-enhanced breast MRI as an adjunct to conventional imaging (mammography, ultrasound) to clarify equivocal findings without microcalcifications. Reference standard for MRI findings had to be established by histopathological sampling or imaging follow-up of at least 12 months. Number of true or false positives and negatives and other characteristics were extracted, and possible bias was determined using the QUADAS-2 applet. Statistical analyses included data pooling and heterogeneity testing., Results: Fourteen out of 514 studies comprising 2,316 lesions met our inclusion criteria. Pooled diagnostic parameters were: sensitivity (99%, 95%-CI: 93-100%), specificity (89%, 95%-CI: 85-92%), PPV (56%, 95%-CI: 42-70%) and NPV (100%, 95%-CI: 99-100%). These estimates displayed significant heterogeneity (P<0.001)., Conclusions: Breast MRI demonstrates an excellent diagnostic performance in case of non-calcified equivocal breast findings detected in conventional imaging. However, considering the substantial heterogeneity with regard to prevalence of malignancy, problem solving criteria need to be better defined.

Background: Previously, a strong positive association between background parenchymal enhancement (BPE) at magnetic resonance imaging (MRI) and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients., Methods: 540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high-risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis)) and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates., Results: Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001) and a weak negative correlation with BPE (r = -0.28, p<0.001). FGT and BPE correlated moderately (r = 0.35, p<0.001). Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046) and BPE (r = -0.156, p<0.001) and weak positive correlation with age (r = 0.353, p<0.001). On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001)., Conclusions: Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting.

Background: Finding a simple, accurate, and noninvasive diagnosis method is a substantial challenge for the detection of Helicobacter pylori. The aim of the present study was to compare the presence of H. pylori urease antigen in saliva with the presence of this bacterium in gastric mucosa., Methods: Saliva samples and gastric biopsies were taken from 153 consenting Moroccan patients. Saliva samples were analyzed using an immunochromatographic test for urease antigen H. pylori detection. Thereafter, the gastric biopsies were analyzed by histology and polymerase chain reaction (PCR) to detect this bacterium., Results: From a total of 153 recruited Moroccan patients, H. pylori was detected in 28 (18.30%), 87 (57.24%), and 69 (45.10%) cases by saliva test, histology, and PCR, respectively. A significant association was observed between the presence of H. pylori antigen in saliva and age. However, no association was found with sex, H. pylori virulence factors, gastric disease outcome, and density of the bacterium on the gastric mucosa. Considering that only 90 patients presented concordant results on H. pylori diagnosis (positive or negative) by both histology and PCR, the immunochromatographic test showed very low sensitivity (29.79%) and high specificity (90.70%). Of these two tests, the positive and negative predictive values were 77.78% and 54.17%, respectively. The accuracy of the test for salivary detection of urease antigen H. pylori was 58.89%., Conclusion: This study demonstrated a low detection rate of H. pylori antigens in saliva compared with the presence of this bacterium in gastric mucosa, suggesting that saliva cannot be used as a suitable sample for the diagnosis of H. pylori in our study population., (Copyright © 2016. Published by Elsevier Taiwan LLC.)

Objectives: To determine the distribution of cervical high-risk human papillomavirus genotypes and their association to cellular abnormalities in women from Fez and its neighborhood., Methods: Women attending the Hassan II University Hospital for cervical pap smears were recruited after an informed consent. Interviews and two cervical samples were performed for each woman. Cervical samples were used for cytological analysis and HPV DNA detection. HPV was typed using a method based on multiplex PCR with fluorescently labeled specific primers followed by capillary electrophoresis. The study was approved by the ethics committee of the Faculty of Medicine and Pharmacy of Fez., Results: The HPV prevalence in the studied population was 43.1% and the most prevalent types were HPV 53 (23 cases); HPV 16 (20 cases); HPV 35 (18 cases); HPV 51 (10 cases) and HPV 56 (7 cases). From the 619 confirmed pap smears, 20% were abnormal. The cytological abnormalities were significantly associated to HPV infection, women age, number of pregnancies and parity (p < 0.05)., Conclusion: More attention should be given to HPV in Morocco because it represents an important public health concern. The distribution of carcinogenic HPV types in the studied population is different from the data in other regions but epidemiological studies in other Moroccan regions are required.

Endothelial cells are often present at inflammation sites. This is the case of endothelial cells of the blood-brain barrier (BBB) of patients afflicted with neurodegenerative disorders such as Alzheimer's, Parkinson's, or multiple sclerosis, as well as in cases of bacterial meningitis, trauma, or tumor-associated ischemia. Inflammation is a known modulator of gene expression through the activation of transcription factors, mostly NF-κB. RLIP76 (a.k.a. RALBP1), an ATP-dependent transporter of electrophile-glutathione conjugates, modulates BBB permeability through the regulation of tight junction function, cell adhesion, and exocytosis. Genes and pathways regulated by RLIP76 are transcriptional targets of tumor necrosis factor alpha (TNF-α) pro-inflammatory molecule, suggesting that RLIP76 may also be an inflammation target. To assess the effects of TNF-α on RLIP76, we faced the problem of choosing reference genes impervious to TNF-α. Since such genes were not known in human BBB endothelial cells, we subjected these to TNF-α, and measured by quantitative RT-PCR the expression of housekeeping genes commonly used as reference genes. We find most to be modulated, and analysis of several inflammation datasets as well as a metaanalysis of more than 5000 human tissue samples encompassing more than 300 cell types and diseases show that no single housekeeping gene may be used as a reference gene. Using three different algorithms, however, we uncovered a reference geneset impervious to TNF-α, and show for the first time that RLIP76 expression is induced by TNF-α and follows the induction kinetics of inflammation markers, suggesting that inflammation can influence RLIP76 expression at the BBB. We also show that MRP1 (a.k.a. ABCC1), another electrophile-glutathione transporter, is not modulated in the same cells and conditions, indicating that RLIP76 regulation by TNF-α is not a general property of glutathione transporters. The reference geneset uncovered herein should aid in future gene expression studies in inflammatory conditions of the BBB.

Background: HPV is the most prevalent sexually transmitted infection and its effect in cancer induction is well documented. HPV infections are mostly asymptomatic, but it is unclear whether HPV infections can result in alterations of reproductive health., Objective: To determine the relationship between human papillomavirus infections and reproductive health in both men and women., Methods: A systematic literature review was performed in PubMed and ScienceDirect data bases from January 1994 through August 2014., Results: HPV infections are shown to be significantly associated to many adverse effects in the reproductive function. These adverse effects were reported in different levels from cells production to pregnancy and may be related to the infecting genotype., Conclusions: It appears from this study that HPV detection and genotyping could be of great value in infertility diagnosis at least in idiopathic infertility cases. Like for the risk of carcinogenesis, another classification of HPV regarding the risk of fertility alteration may be considered after deep investigations.

Background: In Morocco, knowledge of cancer risk factors, a crucial element in the process of behavioral change, has never been evaluated. This study aims to provide information on the level of awareness of cancer risk factors among the Moroccan general population., Methods: A cross sectional survey was carried out in May 2008, using a stratified sampling method in a representative sample of the Moroccan adult population. The used questionnaire included social and demographic data as well as questions about 14 cancer related factors regarding passive or active smoking, alcoholic beverages, obesity, physical inactivity, food coloring, red meat, fat, salt, fruit, vegetables, olive oil, green tea, coffee, breast-feeding. Subjects had to choose between 3 propositions for each proposed factor (risk factor/Protective factor/Don't Know). The knowledge score was calculated by summing the correct answer for each proposed factor except coffee and food coloring. The answer was assigned 1 if it's correct or 0 if it was incorrect or the participant responded 'don't know. The maximum knowledge score was 12. Multivariate linear regression model was used to evaluate the determinants of knowledge score., Results: Among 2891 subjects who participated to the survey, 49.5% were men and 42% were from a rural area. The mean age was 41.6 ± 15.2 years. The mean knowledge score of cancer related factors was 8.45 ± 3.10 points. Knowledge score increased with educational level (β = -0.65 if school year ≤6 versus >6) and housing category (β = 1.80 in high standing housing vs rural housing). It was also higher in urban area, among never smokers and among people never consuming alcohol compared to others groups., Conclusion: These results provide valuable information necessary to establish relevant cancer prevention strategies in Morocco aiming to enhance and improve people's knowledge about risk factors especially in some target groups.

Human papillomavirus (HPV) detection and genotyping are determinant in cervical cancer prevention. They help to identify women at risk and allow the establishment of epidemiologic profiles. Many PCR-based genotyping methods have been developed. They require many steps or specialized equipment increasing the assay duration and cost. This affects their routine use, especially in developing countries. Therefore, the aim of this study was to develop a new HPV genotyping method that can be routinely used also in low incomes countries. For this purpose, fifteen high risk HPV type specific reverse primers were designed on L1 gene and fluorescently labeled. These primers were used on two multiplex PCR with one common forward primer (MY11). The lengths of products were revealed by capillary electrophoresis. This technique identifies sixteen high risk HPVs (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 68, 73 and 82). It was optimized on HPV genome plasmids and evaluated on artificial and cervical samples. All the sixteen targeted genotypes were identified specifically and repeatedly in simple and multiple infections in both artificial and clinical samples. The developed technique is sensitive, specific, easy to perform and appropriate for routine laboratory use and high throughput screening programs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

H. pylori persistent infection induces chronic gastritis and is associated with peptic ulcer disease and gastric carcinoma development. The severity of these diseases is related to human's genetic diversity, H. pylori genetic variability and environmental factors. To identify the prevalence of histo-pathological damages caused by H. pylori infection in Moroccan population, and to determine their association to H. pylori genotypes, a prospective study has been conducted during 3 years on patients attending the gastroenterology department of Hassan II University Hospital (CHU) of Fez, Morocco. A total of 801 Moroccan adults' patients were recruited; H. pylori was diagnosed and genotyped by PCR in biopsy specimens and histological exam was performed. We found a high rate of glandular atrophy. Chronic inflammation, neutrophil activity and glandular atrophy showed statistically significant association with H. pylori infection. However, intestinal metaplasia was inversely associated to this infection and no association was observed with gastric cancer cases. A statistically significant association was found between intestinal metaplasia and vacAs1 and vac Am1 genotypes in patients aged 50 years and more but not in younger. This last genotype is also associated to gastric cancer. In this study, gastric cancer showed no significant association with H. pylori. Further studies are warranted to determine the role of other etiological agents such as Epstein-Barr virus, human papillomavirus and possibly environmental and dietetic factors in the occurrence of this pathology.

Introduction: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. In Morocco, published studies regarding the prevalence of H. pylori are limited, and to our knowledge, there are no data regarding the reinfection rate of H. pylori after successful treatment., Aim: The aim of this study was to determine the prevalence of H. pylori in our area, and the reinfection rate at 6 months and 1 year of follow-up after successful eradication., Methods: Consecutive patients with investigated ulcer or non-ulcer dyspepsia were prospectively enrolled in the Hassan II University Hospital of Fez. Patients with H. pylori infection were treated with a 1-week triple therapy or 10 day sequential therapy. Those tested urea breath test negative after 3 months of treatment were followed prospectively with repeated urea breath test at 6 months and 1 year. H. pylori status at endoscopic examination was determined by rapid urease test, histology, and culture., Results: Four hundred and twenty-nine patients were enrolled in the study, among them 324 patients (75.5%) presented with H. pylori infection. Two hundred and fifty-six (83.3%) patients had successfully eradicated H. pylori following treatment, among them, two patients (0.8%) were reinfected with H. pylori over 12 months. The rate of reinfection was 0.42% in the first 6 months and of 0.45% in the first year of the study., Conclusion: The results of the present study demonstrate that firstly, prevalence of H. pylori is high (75.5%) in our area, secondly as in developed countries, there is a low (0.8%) but continuous risk of H. pylori infection in adulthood. A different approach for follow-up after H. pylori eradication is probably needed in patients of developing countries, since reinfection prevalence is different between countries., (Copyright © 2013. Published by Elsevier Masson SAS.)

Staphylococcus aureus, which has its ecological niche in the anterior nares, has been shown to cause a variety of infectious diseases mainly for patients in hemodialysis units. We performed this study to evaluate the prevalence of nasal S. aureus carriage among hemodialysis outpatients, to determine the antimicrobial susceptibility of isolates, to characterize the virulence genes, and to identify associated risk factors. Nares swab specimens were obtained from 70 outpatients on hemodialysis between March and June 2010. Samples were plated immediately onto S. aureus specific media and pattern of antibacterial sensitivity was determined using disk diffusion method. Polymerase chain reaction was used to detect nuc, mecA, and genes encoding staphylococcal toxins. Medical record of patients was explored to determine S.aureus carriage risk factors. Nasal screening identified 42.9% S. aureus carriers with only one (3.3%) methicillin-resistant S. aureus isolate. Among the methicillin-susceptible S. aureus isolates, high rate of penicillin resistance (81.8%) has been detected. The identified risk factors were male gender and age ≤ 30 years. Research of virulence factors showed a high genetic diversity among the 30 S. aureus isolates. Twenty-one (70%) of them had at least one virulence gene, of which 3.3% were Panton-Valentine leukocidin (lukS/F-PV) genes. S. aureus carriage must be screened for at regular intervals in hemodialysis patients. Setting up a bacterial surveillance system is one of the strategies to understand the epidemiology of methicillin-resistant S. aureus, to guide local antibiotic policy and prevent spread of antibiotic-resistant S. aureus., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)

Objective: The aim of this study was to assess and compare the efficacy and safety of sequential treatment with standard triple therapies in a located population in Morocco., Methods: Consecutive H. pylori-positive patients with endoscopy-proven ulcer or non ulcer dyspepsia were prospectively randomized in the trial into one of three groups: AM and AC group were administered a tri-therapy for 7 days including PPI + amoxicillin + metronidazole (AM group)/clarithromycin (AC group) and SQ group was administered a sequential regimen consisting of PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for the remaining 5 days. Eradication was confirmed by 13C-urea breath test 3 months after the end of the treatment., Results: Groups AM, AC and SQ included respectively 104, 115 and 104 patients. They were comparable in terms of age, sex, clinical and endoscopic presentation. The rate of H. pylori eradication with sequential therapy was found at 94.2% (n=98) in ITT and 96% (n=98) in PP. It was higher than those found in the AM group: 70% (n=73) in ITT and 70.8% (n=73) in PP and the AC group: 78.2% (n=90) in ITT and 79.6% (n=90) in PP (0.001). The prevalence of side effects following the sequential treatment was 9.6% (n=10) versus 22% (n=22) and 27.8% (n=32) in the AM and AC groups, respectively, (P=0.006)., Conclusions: Sequential treatment was better tolerated and achieved a significantly higher eradication rate of H. pylori compared with standard triple therapies in this population., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM22-52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target.

Helicobacter pylori infection is the etiologic agent of various gastric pathologies. The severity of disease outcome has been attributed to some H. pylori genotypes, which varies geographically. In Morocco, there are no data regarding the pattern of H. pylori genotypes; therefore, this is the first prospective study conducted in our country to investigate the genotype profiles (vacA and cagA) of H. pylori in patients with gastric pain. Endoscopic biopsies were obtained in patients attending the gastroenterology department of the Hospital University Hassan II of Fez for gastric pain and were directly used for H. pylori detection and genotyping by polymerase chain reaction (PCR). The SPSS software program was used to study the genotype correlation to different clinical outcomes. A total of 429 patients were included in this study, with an infection rate of 69.9%. cagA was detected in 42.3% of cases. However, vacA genotyping reveal a large predominance of s2m2. Infection with multiple strains was detected in 10.8% of cases and incomplete vacA was observed in 31.5%. In Morocco, vacA s1m1 was significantly associated to peptic ulcer diseases, while s2m2 was associated to gastritis. Moroccan H. pylori vacA genotype profiles differ from the Latin American, European, and South African profiles, with more similarities to the North African profile. Because of the small number of cases with gastric cancer, no correlations with H. pylori have been studied, so, further studies will be required in order to highlight the effects of those genes on this disease.

Background: Morbihan's disease (MD), also known as 'persistent facial oedema' or 'rosaceous lymphoedema', is an uncommon facial condition that is difficult to treat. Its cause remains unclear., Aim: We report three new cases of solid persistent facial oedema, which, after treatment with furosemide, showed dramatic improvement., Patients and Methods: Three men (respectively aged 38, 66 and 76 years) presented Morbihan's disease progressing respectively for 2, 5 and 8 years. These patients presented with facial oedema, mainly affecting the eyelids. The diagnosis of MD was based on clinical and laboratory criteria (after exclusion of other aetiologies such as sarcoidosis, lupus erythematosus, facial demodicidosis and rosacea). After several unsuccessful treatments (tetracyclines, synthetic antimalarials, danazol, systemic steroids and isotretinoin), the patients received diuretics: furosemide (60 mg/d) in two cases and spironolactone 75 mg twice daily for the third patient. The patients were evaluated after 1 month, then every 3 months., Results: Regression of oedema was complete or almost complete with follow-up of between 1 and 16 years. No adverse effects were reported., Discussion: Treatment of Morbihan's disease remains difficult and empirical. Diuretics may be of value since they help significantly reduce swelling even if they do not definitely cure patients., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Epidemiological studies have shown the association between risk of developing cervical cancer and the persistence of high-risk papillomavirus types in addition to some co-factors. However, little is known about co-factors associated with human papillomavirus (HPV) infection, especially in developing countries. This study aims to determine HPV status and associated risk factors in women with normal cytology living in the north-central area of Morocco., Methodology: From February 2007 to December 2008, a total of 925 women consulting in the gynaecological department of Fez University Hospital were asked about sociodemographic characteristics and reproductive and sexual health. Cervical samples were collected for cytological examination and HPV DNA detection. Data collected from 751 women with normal cytology were used in this study to assess the correlation between HPV infection and potential risk factors., Results: High prevalence of HPV infection was detected (42.5%). The highest infection rate was observed in women aged > 45 years and in those with history of abortion (OR:3.76; 95%CI[1.77-7.98]) fibroma, polyp or cysts (OR:1.68; 95%CI[1.07-2.65]). No significant association was detected with other reproductive health and risk factors including oral contraception., Conclusion: In spite of the insignificant association of HPV infection with age, health authorities should seriously consider and implement strategies to increase and maintain a cervical cancer screening programme in women aged 45 and above. More attention must be given to women with gynaecological history (abortion, fibroma, polyp or cysts) since these events may be predictors of HPV infection. Investigations on partner sexual behaviour and some specific hygienic habits, especially public Turkish bath use, are needed to clarify the HPV incidence in this region.

In the course of our validation program testing blood-brain barrier (BBB) in vitro models for their usability as tools in drug discovery it was evaluated whether an established Transwell model based on porcine cell line PBMEC/C1-2 was able to differentiate between the transport properties of first and second generation antihistaminic drugs. First generation antihistamines can permeate the BBB and act in the central nervous system (CNS), whereas entry to the CNS of second generation antihistamines is restricted by efflux pumps such as P-glycoprotein (P-gP) located in brain endothelial cells. P-gP functionality of PBMEC/C1-2 cells grown on Transwell filter inserts was proven by transport studies with P-gP substrate rhodamine 123 and P-gP blocker verapamil. Subsequent drug transport studies with the first generation antihistamines promethazine, diphenhydramine and pheniramine and the second generation antihistamines astemizole, ceterizine, fexofenadine and loratadine were accomplished in single substance as well as in group studies. Results were normalised to diazepam, an internal standard for the transcellular transport route. Moreover, effects after addition of P-gP inhibitor verapamil were investigated. First generation antihistamine pheniramine permeated as fastest followed by diphenhydramine, diazepam, promethazine and second generation antihistaminic drugs ceterizine, fexofenadine, astemizole and loratadine reflecting the BBB in vivo permeability ranking well. Verapamil increased the transport rates of all second generation antihistamines, which suggested involvement of P-gP during their permeation across the BBB model. The ranking after addition of verapamil was significantly changed, only fexofenadine and ceterizine penetrated slower than internal standard diazepam in the presence of verapamil. In summary, permeability data showed that the BBB model based on porcine cell line PBMEC/C1-2 was able to reflect the BBB in vivo situation for the transport of antihistaminc drugs and to distinguish between first and second generation antihistamines.

Several gene databases, including heavily used ones such as the National Center for Biotechnology Information (NCBI) database, erroneously assign, on occasion, literature references to genes or proteins. These mistakes are mostly due to an overlap in gene aliases, whereby two distinct genes share a pseudonym. This is particularly confusing when the gene products have also biological properties in common, are part of signaling pathways that cross-talk to one another, or are regulated by the same effectors. We present examples spanning several research fields including apoptosis, ubiquitin-dependent degradation, signaling by Notch, Wnt, and small G proteins, transporters of glutathione conjugates of electrophiles, and mitochondrial and ribosomal RNA genes. To solve the problem, we argue in favor of including Entrez gene numbers in papers submitted for publication as unique gene identifiers to allow precise identification of genes and species studied., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The RAS/RAF/MEK/MAP kinase cascade transduces signals from the cell surface to the nucleus in order to control cellular responses including proliferation, differentiation and survival. We investigated the occurrence of BRAF exon 15 and KRAS codon 12 and 13 mutations in Moroccan patients with colorectal cancer., Methods: Sixty-two samples from patients with sporadic colorectal adenocarcinomas were studied for BRAF exon 15 and KRAS codon 12 and 13 mutations. DNA from paraffin-embedded tissue specimens was analyzed by a combination of polymerase chain reaction-high resolution melting and direct sequencing., Results: Of the analyzed specimens, 29% exhibited KRAS codon 12 or 13 mutations and only 1.6% carried a BRAF codon 600 mutation. KRAS mutations were more often observed in women (35.5%) than in men (22.6%). Patients in the age range between 41 and 60 years were more likely to be carriers of this mutation. No KRAS mutations were detected in patients aged >60 years., Conclusion: Despite the limited study sample, our data suggest that KRAS mutations arise more frequently than BRAF mutations in Moroccan patients with colorectal carcinomas. The KRAS mutation status must be assessed in a large cohort of Moroccan patients to confirm these findings and to determine whether this mutation in combination with extrinsic, environmental or microenvironmental factors might be involved in the high frequency of colorectal cancer in middle-aged Moroccans.

Since passive immunization with serum-derived immunoglobulins (intravenous immunoglobulins) showed several positive effects in some patients with Alzheimer's disease (AD), intravenous immunoglobulins (IVIG) are discussed as a possible treatment option. IVIG, an antibody product derived from human plasma, contains natural antibodies against amyloid beta(Abeta) peptide. Until now it is not known, how IVIG interferes with pathogenesis in AD, but several proposed mechanisms are in discussion. Receptor types which are involved in transport processes at the BBB are LRP, RAGE and hFcRn. We were looking for an in vitro BBB model expressing these receptors and studied the alteration of transport of Abeta peptides across this model under the influence of immunoglobulins. Cell line ECV304 was found to be suitable for our experiments. We found evidence for involvement of an improved clearance of Abeta across the BBB as well as a decreased Abeta influx from blood to the brain probably following complex formation of immunoglobulins with free Abeta in the periphery. Furthermore, we were able to confirm the activity of IVIG preparations which acted the same way but showed slightly less efficacy in comparison to monoclonal anti-Abeta antibodies. Based on these results we suggest multiple mechanisms responsible for the efficacy of immunotherapy in Alzheimer's disease.

The blood-brain barrier (BBB) maintains the homeostasis between the central nervous system and the blood circulation. One of the main efflux transporter proteins at the BBB is P-glycoprotein (P-gP) also known as ABCB1 or MDR1. Due to the important role of P-gP for the transport barrier function of the BBB, the presence and functionality of P-gP was investigated in porcine cell line PBMEC/C1-2. Presence of P-gP was confirmed on the protein level by western blotting and immunofluorescence microscopy as well as on the mRNA level by qPCR. Functional assessment was accomplished by an established 96-well uptake assay using Rhodamine 123 and Doxorubicin as P-gP substrates and Verapamil as moderate P-gP inhibitor. In this regard, fluorescence microscopy confirmed a significant higher uptake of Rhodamine 123 into PBMEC/C1-2 cells when preincubated with Verapamil. Finally, knock-down of P-gP by antisense oligonucleotides revealed an increase of Rhodamine 123 uptake indicating decreased P-gP functionality. In summary, the presence and functionality of P-gP in the immortalised cell line PBMEC/C1-2 was proven with several techniques and assays. Thus, this cell line could be used for P-gP studies in the context of BBB relevant issues., ((c) 2009 Elsevier Ireland Ltd. All rights reserved.)

A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'-bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di-carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex (11) showed remarkable activity against MBT as compared to other complexes, (1-10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile derivatives, appears to play a key role in the antitubercular potency of this new class of metal-based compounds.

The title compound, C(25)H(20)N(2)O(4), is a new spiro-isoxazoline derivative. It contains a five-membered isoxazoline ring (A), a tetra-lone unit (E and D), a 4-nitro-phenyl substituent (B), and a phenyl ring (C). The isoxazoline ring (A) has an envelope conformation, while the cyclo-hexenone ring (D) has an inter-mediate sofa/half-chair conformation. The aromatic ring of the 4-nitro-phenyl substituent (B) is inclined at an angle of 78.97 (10)° to the phenyl ring (C). The rigid pharmacophore site, Osp(2)-C-C-Osp(3), is characterized by an O⋯O distance of 3.113 (2) Å and an O-C-C-O torsion angle of 97.8 (2)°. In the crystal structure, mol-ecules are linked by C-H⋯O contacts.