Search

Context: The computerization of both fetal heart rate (FHR) and intelligent classification modeling of the cardiotocograph (CTG) is one of the approaches that are utilized in assisting obstetricians in conducting initial interpretation based on (CTG) analysis. CTG tracing interpretation is crucial for the monitoring of the fetal status during weeks into the pregnancy and childbirth. Most contemporary studies rely on computer-assisted fetal heart rate (FHR) feature extraction and CTG categorization to determine the best precise diagnosis for tracking fetal health during pregnancy. Furthermore, through the utilization of a computer-assisted fetal monitoring system, the FHR patterns can be precisely detected and categorized., Objective: The goal of this project is to create a reliable feature extraction algorithm for the FHR as well as a systematic and viable classifier for the CTG through the utilization of the MATLAB platform, all the while adhering to the recognized Royal College of Obstetricians and Gynecologists (RCOG) recommendations., Method: The compiled CTG data from spiky artifacts were cleaned by a specifically created application and compensated for missing data using the guidelines provided by RCOG and the MATLAB toolbox after the implemented data has been processed and the FHR fundamental features have been extracted, for example, the baseline, acceleration, deceleration, and baseline variability. This is followed by the classification phase based on the MATLAB environment. Next, using the guideline provided by the RCOG, the signals patterns of CTG were classified into three categories specifically as normal, abnormal (suspicious), or pathological. Furthermore, to ensure the effectiveness of the created computerized procedure and confirm the robustness of the method, the visual interpretation performed by five obstetricians is compared with the results utilizing the computerized version for the 150 CTG signals., Results: The attained CTG signal categorization results revealed that there is variability, particularly a trivial dissimilarity of approximately (+/-4 and 6) beats per minute (b.p.m.). It was demonstrated that obstetricians' observations coincide with algorithms based on deceleration type and number, except for acceleration values that differ by up to (+/-4)., Discussion: The results obtained based on CTG interpretation showed that the utilization of the computerized approach employed in infirmaries and home care services for pregnant women is indeed suitable., Conclusions: The classification based on CTG that was used for the interpretation of the FHR attribute as discussed in this study is based on the RCOG guidelines. The system is evaluated and validated by experts based on their expert opinions and was compared with the CTG feature extraction and classification algorithms developed using MATLAB., Competing Interests: The authors declare that they have no competing interests., (© 2022 Al-yousif et al.)

Background and Purpose: Patients with rectal cancer could avoid major surgery if they achieve clinical complete response (cCR) post neoadjuvant treatment. Therefore, prediction of treatment outcomes before treatment has become necessary to select the best neo-adjuvant treatment option. This study investigates clinical and radiomics variables' ability to predict cCR in patients pre chemoradiotherapy., Materials and Methods: Using the OnCoRe database, we recruited a matched cohort of 304 patients (152 with cCR; 152 without cCR) deriving training (N = 200) and validation (N = 104) sets. We collected pre-treatment MR (magnetic resonance) images, demographics and blood parameters (haemoglobin, neutrophil, lymphocyte, alkaline phosphate and albumin). We segmented the gross tumour volume on T2 Weighted MR Images and extracted 1430 stable radiomics features per patient. We used principal component analysis (PCA) and receiver operating characteristic area under the curve (ROC AUC) to reduce dimensionality and evaluate the models produced., Results: Using Logistic regression analysis, PCA-derived combined model (radiomics plus clinical variables) gave a ROC AUC of 0.76 (95% CI: 0.69-0.83) in the training set and 0.68 (95% CI 0.57-0.79) in the validation set. The clinical only model achieved an AUC of 0.73 (95% CI 0.66-0.80) and 0.62 (95% CI 0.51-0.74) in the training and validation set, respectively. The radiomics model had an AUC of 0.68 (95% CI 0.61-0.75) and 0.66 (95% CI 0.56-0.77) in the training and validation sets., Conclusion: The predictive characteristics of both clinical and radiomics variables for clinical complete response remain modest but radiomics predictability is improved with addition of clinical variables., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background: Uptake of health checks among women has not been examined in relation to patient and General Practitioner (GP) practice level factors. We investigated patient and practice level factors associated with differential uptake of health checks., Methods: Primary care records from 44 practices in Lambeth for women aged 40-74 years old ( N  = 62,967) from 2000-2018 were analysed using multi-level logistic regression models. An odds ratio (OR) >1 indicates increased occurrence of no health check., Findings: The mean age (IQR) of the included female sample (aged 40-74 years) was 52.9 years (45.0-59.0). Adjusted for patient-level factors (age, ethnicity, English as first language, overweight/obesity, smoking, attendance to GP practices, and co-morbidity), the odds of non-uptake of health checks were higher for Other White (OR 1.24, 95% confidence interval 1.17-1.33), and Other ethnicity (1.20, 1.07-1.35) vs. White British. It was also higher for 50-69 year olds (1.55, 1.47-1.62), 70-74 year olds (1.60, 1.49-1.72) vs. 40-49 year olds. These ORs did not change on adjustments for practice level factors (proportion of patients living in deprived areas, proportion of patients with ≥1 chronic condition, ≥3 emergency diabetes admissions annually, GP density/1000 patients, quality outcome framework score of ≥ 95%, and patient satisfaction scores of ≥80%). Non-uptake was lower for Black Caribbeans, Bangladeshis, overweight/obese patients, frequent practice attenders and comorbid patients., Interpretation: Differential uptake in health checks remained after adjustment for patient and practice level factors. Better measures of social determinants of health and of practice context are needed., Funding: NIHR Research for Patient Benefit Programme (NIHR202769)., Competing Interests: None., (© 2022 The Authors.)

In the present research work, 2D-Porous NiO decorated graphene nanocomposite was synthesized by hydrothermal method to monitored the concentration of epinephrine (EPI). The morphology (SEM and TEM) results confirmed 2D-Porous NiO nanoparticles firmly attached over graphene nanosheets. FTIR and XPS analysis confirmed the formation of nickel oxide formation and complete reduction of GO to rGO. The electrochemical activity of the proposed NiO-rGO/GCE modified electrode on epinephrine was analyzed by simple cyclic voltammetry technique. The proposed low cost NiO-rGO/GCE modified electrode showed excellent catalytic activity over GCE and rGO/GCE electrodes. Due to its high conductivity and charge transfer ability of the NiO-rGO/GCE modified electrode exhibited high sensitivity of EPI at optimized conditions. The anodic peak current of the EPI linearly increases with increasing the concertation of EPI. A wide linear range (50 μM-1000 μM) was achieved with high correlation coefficient (R 2  = 0.9986) and the limit of detection (LOD) of NiO-rGO/GCE modified electrode was calculated to be 10 μM. NiO-rGO/GCE electrode showed good stability and repeatability towards the EPI oxidation. Mainly, the proposed NiO-rGO/GCE modified electrode showed good sensitivity of EPI in the human biological fluid with high recovery percentage. The low cost, NiO-rGO/GCE electrode could be the promising sensor electrode for the detection of Epinephrine in the real samples., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The association of malnutrition with congenital heart disease (CHD) is well documented. Studies comparing the effects of parenteral nutrition (PN) and enteral feeding (EF) on the post-surgical correction of CHD are not available. We compared the effects of PN with EF on the nutritional status of children post-cardiac surgery., Methods: A retrospective cohort study was conducted with 72 children aged ≤6 years who had at least one heart surgery between 2010 and 2016. Malnutrition was defined as a weight for height Z-score (WHZ) below -2. The primary endpoint was the change in the mean WHZ Z-score from the baseline. All statistical analyses were performed using SPSS 21.0 [Release 21.0.0.0, IBM, USA]., Results: The sample size realized as 72 ( n = 72). The overall prevalence of malnutrition was 48%. The change in height of the PN group was significantly higher than the EF group (14.2 ± 7.6 cm vs. 7.4 ± 6.3, P = 0.010), but the weight change was not significantly different ( P = 0.28). The post-surgery Z-scores were significantly lower in the PN group and the Z-score change was marginally smaller ( P = 0.086), indicating lower growth levels post-surgery. The PN group had a significantly higher incidence of post-surgical malnutrition ( P = 0.046). Patients who received PN had significantly less improvement (more negative change) in the Z-score levels compared to the EF group (PE = -1.42, 95% confidence interval [CI] = [-2.48, -0.35]; P = 0.011)., Conclusion: Malnutrition occurs frequently with CHD. PN does not add any nutritional benefits compared with EF. EF should always be the preferred method of nutrition unless contraindicated., (Copyright: © International Journal of Health Sciences.)

Context: The interpretations of cardiotocography (CTG) tracings are indeed vital to monitor fetal well-being both during pregnancy and childbirth. Currently, many studies are focusing on feature extraction and CTG classification using computer vision approach in determining the most accurate diagnosis as well as monitoring the fetal well-being during pregnancy. Additionally, a fetal monitoring system would be able to perform detection and precise quantification of fetal heart rate patterns., Objective: This study aimed to perform a systematic review to describe the achievements made by the researchers, summarizing findings that have been found by previous researchers in feature extraction and CTG classification, to determine criteria and evaluation methods to the taxonomies of the proposed literature in the CTG field and to distinguish aspects from relevant research in the field of CTG., Methods: Article search was done systematically using three databases: IEEE Xplore digital library, Science Direct, and Web of Science over a period of 5 years. The literature in the medical sciences and engineering was included in the search selection to provide a broader understanding for researchers., Results: After screening 372 articles, and based on our protocol of exclusion and inclusion criteria, for the final set of articles, 50 articles were obtained. The research literature taxonomy was divided into four stages. The first stage discussed the proposed method which presented steps and algorithms in the pre-processing stage, feature extraction and classification as well as their use in CTG (20/50 papers). The second stage included the development of a system specifically on automatic feature extraction and CTG classification (7/50 papers). The third stage consisted of reviews and survey articles on automatic feature extraction and CTG classification (3/50 papers). The last stage discussed evaluation and comparative studies to determine the best method for extracting and classifying features with comparisons based on a set of criteria (20/50 articles)., Discussion: This study focused more on literature compared to techniques or methods. Also, this study conducts research and identification of various types of datasets used in surveys from publicly available, private, and commercial datasets. To analyze the results, researchers evaluated independent datasets using different techniques., Conclusions: This systematic review contributes to understand and have insight into the relevant research in the field of CTG by surveying and classifying pertinent research efforts. This review will help to address the current research opportunities, problems and challenges, motivations, recommendations related to feature extraction and CTG classification, as well as the measurement of various performance and various data sets used by other researchers., Competing Interests: The authors declare there are no competing interests., (©2021 Al-yousif et al.)

The frequency of nonsurgical rhinoplasty has increased in recent years. The occurrence of headaches or migraine symptoms, and their treatment following nonsurgical rhinoplasty, have been scarcely described in the literature. Here, we present a patient who presented with subjective complaints of a new onset headache immediately after nonsurgical rhinoplasty, with subsequent reversal of her symptoms using hylauronidase. Furthermore, a literature review was conducted to establish a possible anatomical pathophysiologic mechanism of these symptoms seen in this patient., Methods: A case report of a patient who developed persistent headache symptoms after nonsurgical rhinoplasty, with reversal of symptoms using hylaronidase, is described. A literature review of studies on patients developing headaches or migraine-like symptoms after nonsurgical rhinoplasty was conducted, along with a review of the anatomic causes of migraines., Results: Of the 147 relevant citations identified in our search, only 1 individual case report describes a patient who developed a migraine headache after undergoing a nonsurgical rhinoplasty via an injection of hyaluronic acid filler. This was promptly resolved with the utilization of a hyaluronidase injection. The majority of the relevant articles in our search focused on the alarming and most feared complication of vascular compromise of the nasal tissue and intravascular embolization. Within the literature, there was no case series of nonsurgical-rhinoplasty-induced migraines taking into account our inclusion criteria., Conclusions: This article demonstrates the paucity of literature regarding nonsurgical-rhinoplasty-induced headaches. Although a causation effect cannot be linked, our study highlights a rare phenomenon associated with this ever-increasing aesthetic procedure., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Stroke is a major emergency that can cause a significant morbidity and mortality. Advancement in stroke management in recent years has allowed more patients to be diagnosed and treated by stroke teams; however, stroke is a time-sensitive emergency that requires a high level of coordination, particularly within the prehospital phase. This research is to determine whether patients received by Emergency Medical Services (EMS) at a tertiary health care facility had shorter stroke team activation, time to computed tomography (CT), or time to receive intravenous thrombolytics., Methods: This research is a prospective cohort study of adults with stroke symptoms who required stroke team activation at a tertiary medical facility. The study included all patients received from September 1, 2017 through August 31, 2018. The primary outcome was the time difference to stroke team activation between patients received by EMS compared to patients that arrived by a private method of transportation. The secondary outcomes were the difference in time to CT scan and the time to receive intravenous recombinant tissue plasminogen activator (rtPA)., Results: There were 75 (34.1%) patients who had been received by EMS, while 145 (65.9%) patients arrived via private transportation method (private car or by a friend/family member). The mean time to stroke team activation, time to CT, and time to receive thrombolytic therapy for the EMS group were: 8.19 (95% CI, 6.97 - 9.41) minutes; 18 (95% CI, 15.9 - 20.1) minutes; and 13.1 (95% CI, 6.95 - 19.3) minutes, respectively. Those for the private car group, on the other hand, were: 16 (95% CI, 12.4 - 19.6) minutes; 23.39 (95% CI, 19.6 - 27.2) minutes; and nine (95% CI, 4.54 -13.5) minutes, respectively. There was a significantly shorter time to stroke team activation for patients arriving via EMS compared to private car (P ≤ .00), but no significant difference was found on time to CT (P = .259) or time to receive rtPA (P = .100)., Conclusion: Emergency Medical Service transportation of stroke patients can significantly shorten the time to stroke team activation, leading to shorter triage and accelerated patient management. However, there was no statistical difference in time to CT or time to receive rtPA. Patients with stroke symptoms may benefit more from EMS transportation compared to private methods of transportation.

Purpose: The aim of this study was to find out the correlation between magnetic resonance imaging (MRI) and nerve conduction studies' (NCS) findings in patients with lumbosacral radiculopathy caused by lumbar intervertebral disc herniation. In addition, the study aimed at finding the correlation between the clinical manifestations of lumbosacral radiculopathy and both MRI and NCS. Patients and Methods . The study was a cross-sectional analytic study which included thirty patients with a history suggestive of lumbosacral radiculopathy. Inclusion criteria were as follows: patients who had an MRI confirmed L4/5 and/or L5/S1 intervertebral disc prolapse in addition to one or more of the following (dermatomal distribution of symptoms appropriate with MRI level, presence of motor weakness, sensory impairment, absent ankle jerk, or positive straight leg raising test). All patients underwent clinical assessment and NCS, and their MRI examination was reviewed. The Chi-Squared/Fisher's exact test was used to test the correlation., Results: There was a statistically significant correlation between abnormal physical findings and nerve root compression in MRI. Statistically significant correlation was neither found between abnormal physical examination findings and abnormal NCS nor between nerve root compression in MRI and abnormal NCS findings., Conclusion: Abnormal neurological examination findings can be used to predict nerve root compression in MRI examination. On the contrary, positive findings of physical examination do not predict abnormal NCS, as well as negative findings do not exclude abnormal NCS; therefore, it is useful to add NCS when MRI findings do not match clinical examination findings or when no neuroimaging abnormalities can be identified., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2020 Safa Yousif et al.)

The effects of glucose on the growth and surface properties of MoS 2 with a nanosheet structure were investigated in detail. In the presence of glucose, the hydrothermal reaction of sodium molybdate and thiourea yields carbon-loaded MoS 2 nanocomposites (C/MoS 2 ). Compared with bare MoS 2 nanosheets with more than six layers obtained in the absence of glucose and carbon spheres with a diameter of 500 nm prepared from the carbonization of glucose, C/MoS 2 consists of one- or three-layered MoS 2 and carbon spheres with a diameter less than 1 nm to give a large Brunauer-Emmett-Teller surface area (3-20 times larger than the individual materials). The surface characterizations reveal that both MoS 2 and carbon spheres of C/MoS 2 have a negative charge on the surface, suggesting that the previously reported explanation, in which the adsorption of MoS 2 and/or molybdate ions on carbon spheres inhibits the growth and aggregation of MoS 2 , is not correct. Based on Fourier transform infrared and 1 H NMR spectra, it is demonstrated that glucose acts as the hydrogen bond donor toward polyoxomolybdate species such as Mo 8 O 26 4- , Mo 7 O 24 6- , and MoO 4 2- in the range of pH = 2-12. The intermolecular hydrogen bond not only inhibits the growth of both the (002) plane of MoS 2 and carbon spheres, but also enables the formation of C-O-Mo bonds in the in situ generated C/MoS 2 . Compared with bare MoS 2 , C/MoS 2 not only show a lower over-potential by 60 mV for the electrocatalytic evolution of hydrogen, but also has a larger mass specific capacitance by three times, due to the larger surface area and the interfacial interaction through the C-O-Mo bonds.

Bertolotti syndrome describes lower back pain secondary to an anatomical lumbosacral transitional vertebrae. We present the case of a 37 year old female with chronic lower back pain with radiological evidence of an anatomical lumbosacral pseudojoint. The patient underwent minimally invasive resection of her pseudojoint with complete resolution of symptoms postoperatively. We, as the authors would like to highlight that in patients with pain secondary to an aberrant lumbosacral articulation, consideration should be given to treatment via a minimally invasive technique., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Non-invasive screening of carboxyhemoglobin saturation (SpCO) in the emergency department to detect occult exposure is increasingly common. The SpCO threshold to consider exposure in smokers is up to 9%. The literature supporting this cutoff is inadequate, and the impact of active smoking on SpCO saturation remains unclear. The primary objective was to characterize baseline SpCO in a cohort of smokers outdoors. Secondary objectives were to explore the impact of active smoking on SpCO and to compare SpCO between smokers and non-smokers., Methods: This was a prospective cohort pilot study in two outdoor urban public areas in the USA, in a convenience sample of adult smokers. SpCO saturations were assessed non-invasively before, during, and 2 min after cigarette smoking with pulse CO-oximetry. Analyses included descriptive statistics, correlations, and a generalized estimating equation model., Results: Eighty-five smokers had mean baseline SpCO of 2.7% (SD 2.6) and peak of 3.1% (SD 2.9), while 15 controls had SpCO 1.3% (SD 1.3). This was a significant difference. Time since last cigarette was associated with baseline SpCO, and active smoking increased mean SpCO. There was correlation among individual smokers' SpCO levels before, during, and 2 min after smoking, indicating smokers tended to maintain their baseline SpCO level., Conclusions: This study is the first to measure SpCO during active smoking in an uncontrolled environment. It suggests 80% of smokers have SpCO ≤ 5%, but potentially lends support for the current 9% as a threshold, depending on clinical context.

There is high public health alert in the Kingdom of Saudi Arabia concerning Zika virus infection. So far, there is no reported outbreak. So are we at risk of this disease? Reviewing the literature of recent outbreaks of other infectious diseases in Saudi Arabia may clarify the situation. It is evident that there is some similarity between Zika and dengue regarding vector ( Aedes aegypti ) which is available in the Kingdom of Saudi Arabia. Furthermore, they have similar transmission process and the required environment for infection. It seems that the Kingdom has learned from previous outbreaks, so they are well prepared to face such challenges. The Saudi Ministry of Health built the command and control center to deal with the pandemic flues. Furthermore, they are trying to create a center for disease control, and they are recruiting local and international experts in monitoring the emerging infections.

Background: Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation., Methods: This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded., Results: A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia., Conclusions: LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.

Introduction Airway management is one of many challenges that medical providers face in disaster response operations. The use of personal protective equipment (PPE), in particular, was found to be associated with higher failure rates and a prolonged time to achieve airway control. Hypothesis/Problem The objective of this study was to determine whether video laryngoscopy could facilitate the performance of endotracheal intubation by disaster responders wearing Level C PPE., Methods: In this prospective, randomized, crossover study, a convenience sample of practicing prehospital providers were recruited. Following standardized training in PPE use and specific training in the use of airway devices, subjects in Level C PPE were observed while performing endotracheal intubation on a stock airway in a Laerdal Resusci-Anne manikin system (Laerdal Medical; Stavanger, Norway) using one of three laryngoscopic devices in randomized order: a Macintosh direct laryngoscope (Welch Allyn Inc.; New York USA), a GlideScope Ranger video laryngoscope (Verathon Medical; Bothell, Washington USA), and a King Vision video laryngoscope (King Systems; Noblesville, Indiana USA). The primary outcome was time to intubation (TTI), and the secondary outcome was participant perception of the ease of use for each device., Results: A total of 20 prehospital providers participated in the study: 18 (90%) paramedics and two (10%) Emergency Medical Technicians-Cardiac. Participants took significantly longer when using the GlideScope Ranger [35.82 seconds (95% CI, 32.24-39.80)] to achieve successful intubation than with the Macintosh laryngoscope [25.69 seconds (95% CI, 22.42-29.42); adj. P<.0001] or the King Vision [29.87 seconds (95% CI, 26.08-34.21); adj. P=.033], which did not significantly differ from each other (adj. P=.1017). Self-reported measures of satisfaction evaluated on a 0% to 100% visual analog scale (VAS) identified marginally greater subject satisfaction with the King Vision [86.7% (SD=76.4-92.9%)] over the GlideScope Ranger [73.0% (SD=61.9-81.8%); P=.04] and the Macintosh laryngoscope [69.9% (SD=57.9-79.7%); P=.05] prior to adjustment for multiplicity. The GlideScope Ranger and the Macintosh laryngoscope did not differ themselves (P=.65), and the differences were not statistically significant after adjustment for multiplicity (adj. P=.12 for both comparisons)., Conclusion: Use of video laryngoscopes by prehospital providers in Level C PPE did not result in faster endotracheal intubation than use of a Macintosh laryngoscope. The King Vision video laryngoscope, in particular, performed at least as well as the Macintosh laryngoscope and was reported to be easier to use. Yousif S , Machan JT , Alaska Y , Suner S . Airway management in disaster response: a manikin study comparing direct and video laryngoscopy for endotracheal intubation by prehospital providers in Level C personal protective equipment. Prehosp Disaster Med. 2017;32(4):352-356.

Objectives: Hepatocellular carcinoma is among the leading causes of cancer death. The Milan criteria are the first and most widely used criteria for selecting patients with hepatocellular carcinoma for a good transplant outcome. Studies have shown that patients with hepatocellular carcinoma outside the Milan criteria have good outcomes if they are successfully downstaged before transplant. We report our experience with locoregional therapy for hepatocellular carcinoma, either for bridging or for downstaging prior to transplant., Materials and Methods: We retrospectively reviewed the electronic charts and our institutional database for adult patients diagnosed with hepatocellular carcinoma between 2001 and 2016. We recorded patient demographics, the type of transplant (living donor or deceased donor), radiologic findings, the type of locoregional intervention, and overall survival., Results: A total of 642 adult liver transplants were performed during the study period (290 living donor and 352 deceased donor), of which 158 (24.6%) were conducted in patients with hepatocellular carcinoma (104 men and 54 women). Hepatocellular carcinoma was associated with hepatitis C in 80 patients (51%), hepatitis B in 44 (28%), and was cryptogenic in 13 (8%). Patients were grouped based on their radiologic staging (within Milan, within and beyond University of California, San Francisco), and subsequently described by whether they received locoregional therapy. Median survival and mortality were noted. Kaplan-Meier survival curves showed no statistically significant difference for patients within the Milan criteria, with or without locoregional therapy (P = .5). When patients within the Milan criteria were combined with patients within the University of California, San Francisco criteria, those who were downstaged from outside the latter criteria had similar survival., Conclusions: We demonstrate that carefully selected patients beyond the Milan criteria and even beyond the University of California, San Francisco criteria can be bridged and downstaged successfully for liver transplant.

Forensic Odontology is a vital component of forensic science and one branch involves the application of dental science to the identification of unknown human remains. The aim of this study is to investigate the discriminatory potential for identification of the radiographic morphology of obturated single root canals. Thirty periapical radiographs of patients having endodontic treatment of single rooted canals were selected randomly from the data bank of the digital X- ray system present in the restorative department, University of Science and Technology, Sudan. The post-operative radiographs were considered as an ant-mortem data "Set 1". Ten radiographs from the thirty were reprinted, labelled from (A-J) and considered as a post-mortem data "Set 2". This post-mortem group of 10 radiographs "Set 2" would be compared with the ante-mortem group of 30 radiographs comprising "Set 1". These two sets of radiographs would be examined by 40 dentally trained personnel. The thirty radiographs comprising "Set 1" and the 10 radiographs comprising "Set 2" were provided to each of the examiners who were asked to match the individual post-mortem radiographs ("Set 2") with the ante-mortem radiographs ("Set1"). The result demonstrated that 34 examiners achieved a success rate of 100%, 4 examiners achieved a success rate of 97.5% (1 mismatch) and 2 examiners achieved a success rate of 95% (2 mismatches). The radiographic images of obturated single-rooted teeth in this study were shown to have highly- specific morphological features. It is proposed that, in cases where the ante and post-mortem radiographs of a single-rooted obturated canal show similar morphology, this commonality of morphology can be used as a tool in the identification process.

Introduction: Bilateral vocal cord palsy is a condition which has many causes (Gupta et al., 2012) [1]. Syringomyelia is an uncommon condition which describes the formation of fluid filled cavity, occupying the spinal cord (Chang, 2003) [2]. It rarely manifests itself as subacute onset of stridor., Presentation of Case: We present the case of a three year old female who presented for evaluation of her speech and language delay, when incidentally it was made note of her loud breathing which had previously been managed as bronchiolitis by her general practitioner. In hospital she was found to have a bilateral vocal cord palsy. Further investigation revealed a large syrinx as well as an associated Arnold Chiari 1 malformation, for which she required neurosurgical decompression., Conclusion: Although uncommon, formation of a syrinx should be considered for patients who present with stridor and reiterates the importance of MRI as an important investigative tool of bilateral vocal cord palsy., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at [http://hivtoolbox2.bio-toolkit.com].

Roadworks (work zones) are a common feature of our urban environment. They have a considerable impact on reducing roadway capacity, causing interruptions and imposing substantial delays to road users, which in turn adds to the cost to society and adverse impact on road safety. Shuttle-lane (alternate one-way working) is one of the most commonly used traffic management arrangements at urban roadworks as most of the urban road network is built up from single carriageway. Despite the importance of this topic, little attention has been paid to studying drivers' behaviour in terms of close following (tailgating) and amber crossing/red light violations at temporary traffic signals. This paper reports on factors affecting aggressive drivers' behaviour using observations from six sites within Greater Manchester, United Kingdom with over 25 h of video recordings of traffic data from around 1500 signal cycles. The findings show that 24% of drivers violate the "two-second rule" of safe following, as recommended in the Highway Code, before approaching the roadworks site compared to 38% violations after crossing the roadworks site. These results of increased tailgating behaviour are consistent across all sites and for both traffic streams and have a direct effect on rear-end collisions or near accidents. Also, the percentages of drivers' non-compliance with temporary traffic signals are higher compared to those for normal signalised junctions. The results show that around 30% of cycles were violated where drivers cross the stop line on the onset of amber and red (18.9% pass through amber and 11.3% run through red lights). Red light violations were categorised under four categories as observed on site (dilemma zone, dilemma zone follower, single violation and group violations). Factors such as site visibility, traffic signals operation (i.e. fixed time or VA) were also reported., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We present a new approach for pathogen surveillance we call Geogenomics. Geogenomics examines the geographic distribution of the genomes of pathogens, with a particular emphasis on those mutations that give rise to drug resistance. We engineered a new web system called Geogenomic Mutational Atlas of Pathogens (GoMAP) that enables investigation of the global distribution of individual drug resistance mutations. As a test case we examined mutations associated with HIV resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing public drug resistance and HIV protein sequence data to examine the distribution of 872 drug resistance mutations in ∼ 502,000 sequences for many countries in the world. We also implemented a broadened classification scheme for HIV drug resistance mutations. Several patterns for geographic distributions of resistance mutations were identified by visual mining using this web tool. GoMAP-HIV is an open access web application available at http://www.bio-toolkit.com/GoMap/project/

Objective: To assess the mode of delivery following previous anal sphincter injury (ASI), and to evaluate the perineal outcome following a vaginal birth., Study Design: Retrospective data search of the hospital Patient Access System on patients who delivered following previous ASI from 2010 to 2012. When a second ASI was sustained, additional information was gathered from the patients' medical notes. Continuous variables were described by counts and percentages and analysed using SPSS version 20., Results: Between January 2010 and July 2012, 138 women with previous ASI delivered at the Rotunda Hospital, of whom 69 (50%) had a spontaneous vaginal delivery (SVD), 13 (9.4%) had an instrumental delivery (11 vacuum, 2 forceps), and 56 (40.6%) had a caesarean section. Of these caesarean sections, 43 (76.8%) were elective, and 13 (23.2%) were emergency. Of the 82 vaginally delivered patients, the majority had a second degree perineal tear or minor lacerations (54/82 and 14/82 respectively) but 11 had a third degree perineal tear following an SVD - a recurrence risk of 13.4%. There was no significant difference in the average birthweight between patients who sustained a second ASI (3644g) compared to those who did not (3680g). None of the patients who had a second ASI developed faecal incontinence symptoms postnatally: two patients developed flatal incontinence which resolved with physiotherapy., Conclusion: This study highlights the importance of individualised antenatal assessment in patients with a previous ASI. They may have a personal preference when considering their mode of delivery. A specialist clinic affords them the opportunity for a detailed discussion. In this study, 86.5% of women who delivered their subsequent baby vaginally did not sustain an ASI, while 13.4% had a repeat ASI following vaginal birth. It is therefore important to counsel regarding the incidence of repeat ASI, but also to emphasise that it is generally impossible to confidently predict recurrence antenatally., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

We report on a rare case of anatomical variations of the infrahyoid muscles with prominent clinical significance. The aberrant anatomy was on the right side of the neck and involved the omohyoid and sternohyoid muscles. The superior belly of the omohyoid was duplicated in width due to an aberrant belly anteriorly and merged with fibers of the inferior belly inferiorly and the sternohyoid muscle medially. An additional aberrant muscle slip extended between the inferior third of the sternohyoid muscle and united with the inferior belly of the omohyoid. The intermediate tendon between the two bellies of the omohyoid was absent, whereas the so-called muscular triangle of the neck was diminished. Due to the arrangement and fusion of myofibers the muscle could be termed as omo-sternohyoid muscle. A profound hematoma was noted in the aberrant muscle at the area overlying the internal jugular vein indicating difficulty in obtaining jugular venous access for catheter placement. Clinicians and surgeons should be aware of muscular anatomic variations when intervening in the lateral neck area as the classical anatomical landmarks might be misinterpreted and confuse.

Subchronic morphine treatment induces P-glycoprotein (P-gp) up-regulation at the blood-brain barrier. This study investigates the rate and extent to which P-gp and breast cancer-resistance protein (Bcrp) increase at the rat blood-brain barrier following subchronic morphine treatment. Rats were given increasing doses of morphine (10-40 mg/kg) or saline i.p. twice daily for 5 days. The brain cortex large vessels and microvessels were then mechanical isolated 6, 9, 12, 24, and 36 h after the last injection. The gene and protein expression of P-gp and Bcrp in morphine-treated and control rats were compared by qRT-PCR and western blotting. The levels of Mdr1a and Bcrp mRNAs were not significantly modified 6 h post morphine, but the Mdr1a mRNA increased 1.4-fold and Bcrp mRNA 2.4-fold at 24 h. P-gp and Bcrp protein expression in brain microvessels was unchanged 6 h post morphine and increased 1.5-fold at 24 h. This effect was more pronounced in large vessels than in microvessels. However, extracellular morphine concentrations of 0.01-10 μM did not modify the expressions of the MDR1 and BCRP genes in hCMEC/D3 human endothelial brain cells in vitro. MK-801 (NMDA antagonist) and meloxicam (cyclo-oxygenase-2 inhibitor) given after morphine treatment completely blocked P-gp and Bcrp up-regulation. Interestingly, misoprostol and iloprost, two well-known agonists of prostaglandin E2 receptors induced both MDR1 and BCRP mRNA levels in hCMEC/D3. Thus, morphine does not directly stimulate P-gp and Bcrp expression by the brain endothelium, but glutamate released during morphine withdrawal may do so by activating the NMDA/cyclo-oxygenase-2 cascade., (© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

The recent identification of drug-metabolizing enzymes cytochrome P450 (CYP) in the human blood-brain barrier (BBB) raises the question of whether these enzymes act in concert with ATP-binding cassette (ABC) transporters to limit the brain distributions of drugs. We recently demonstrated several CYP genes in freshly isolated human brain microvessels; the main isoforms expressed were CYP1B1 and CYP2U1. Many studies using different experimental approaches have revealed that P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and the multidrug resistance-associated protein 4 (MRP4, ABCC4) are the main ABC transporters in the human BBB. The first part of this review covers recent studies on the expression, regulation and function of CYP450 and ABC transporters in the rodent and human BBBs. The second part focuses on the possible interplay between some CYPs and certain ABC transporters at the BBB, which makes it a determining element of brain drug concentrations and thus of the effects of centrally acting drugs.

Background: AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels., Methods: Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ9-tetrahydrocannabinol (Δ9-THC)., Results: After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression, Conclusions: Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

Diabetes mellitus is increasing in its incidence and prevalence. Reduction in refined carbohydrate (sugar) intake is an important part of nutritional advice to patients with known diabetes. Sugar is available in a variety of confectionary products. It is also available in especially packaged 'convenience foods' as high energy drinks. Among people without diabetes, such food can have its own health risks. A significant group of patients with diabetes remain undiagnosed. This group are at especially high risk from all the negative metabolic effects of high sugar intake available as high calorie drinks. The authors report two patients without previously known diabetes who presented similarly with marked hyperglycaemic states, leading to severe metabolic disturbances. Both were obese, had common precipitating factors and consumed large quantities of sugary soft drinks ('lucozade'). Both patients recovered well. They were followed up for over 7 years. One is not diabetic and the second is diabetic requiring a small dose of metformin.

We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic solute (OST) transporters, 34 ATP-binding cassette (ABC) transporters, and 51 metabolizing enzymes in human brain microvessels. We used quantitative RT-PCR and LC-MS/MS to examine isolated brain microvessels and cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels; ABCG2/BCRP was 1.6-fold more expressed than ABCB1/MDR1, and ABCC4/MRP4 was 10 times less abundant than ABCB1/MDR1. CYP1B1 and CYP2U1 were the only quantifiable CYPs. Finally, GSTP1, COMT, GSTM3, GSTO1 and GSTM2 proteins were the main phase II enzymes quantified; UGTs and NATs were not detected. Our extensive investigation of gene and protein patterns of transporters and metabolizing enzymes provides new molecular information for understanding drug entry and metabolism in the human blood-brain barrier.

Purpose: To evaluate the influence of diabetes mellitus (DM), chronic renal failure (CRF), and malignancies on the rate of bacteriuria and double J ureteric stent bacterial colonization., Patients and Methods: One hundred and twenty patients were included in this prospective study. Midstream urine samples for culture were obtained before ureteric stent insertion. Patients with negative culture were given ciprofloxacin 500 mg orally q 12 h for 5 days as a prophylaxis. All the stents were removed or changed as indicated after having voided midstream urine sample for culture on the day of stent removal. Stents were sent for culture. Culture was obtained from the outer surface of the stent by gentle scraping with a sterile scalpel. Significant bacteriuria was defined as a count of colony-forming units per milliliter of urine of >10(5)., Results: The patients were between 20 and 74 years of age (mean 42.5 + or - 13) and the duration of stent insertion ranged between 14 and 120 days (52.5 + or - 7.2). In 29 patients (24.2%), double J stent bacterial colonization was positive (12 males and 17 females). Of these patients, 27 (22.5%) had positive urine cultures (11 males and 16 females). The most commonly isolated pathogen was Escherichia coli. DM, CRF, or malignancies showed a higher risk for bacteriuria and stent bacterial colonization., Conclusion: Immune-compromising diseases such as DM, CRF, and malignancies are proved to be risk factors for urinary tract infection and stent colonization in patients with ureteric stent insertion. Stent cultures are not needed as the same microorganisms grow in urine cultures.

Background: Life satisfaction is widely considered to be a central aspect of human welfare. Many have identified happiness with it, and some maintain that well-being consists largely or wholly in being satisfied with one's life. Empirical research on well-being relies heavily on life satisfaction studies., Aims: The aim of this study was to examine the relationships of psychiatric disorders and physical disorders on life satisfaction among Arab older adults in general population., Methods: Face-to-face interviews with Geriatric Mental State Interview (GMS-A3) were conducted with a nationwide sample of 2000 household in 2001. Total samples of 610 elders (above 60 years) were interviewed., Results: There were 347 males (56.9%) and 263 females (43.1%). The mean age was 68.6 years (SD = 8.3). The commonest diagnoses were depression (20.2%), anxiety (5.6%), hypochondriasis (4.4%), and organic brain syndrome with or without dementia (3.6%). The findings suggest that having depressive disorder was significantly associated with less life satisfaction in the whole sample of older adults' people. In addition, anxiety, hypochondriacal disorders, and organic brain syndrome were significantly associated with low life satisfaction. Meanwhile, other psychiatric disorders e.g., phobia, Obsessive Compulsive disorder (OCD), schizophrenia were not significantly associated with life satisfaction. No significant relationship was found with any physical disorders alone. The data further reveal that low level of life satisfaction was especially significant in the age group above 85 years and people who live alone or only with wife/husband., Conclusions: The strong influence of psychiatric disorders e.g., depression, anxiety, organic brain syndrome, and hypochondriasis rather than physical disorders suggests that a lack of meaning and worries are more detrimental to life satisfaction than physical frailty. The findings underscore the need to develop interventions that help older people deal more effectively with psychiatric disorders and its comorbidities. Moreover, the results suggest that providing family support, by not allowing older adults to live alone, may be especially helpful for older adults.

Thousands of Sudanese refugees have fled to Cairo, Egypt in the wake of Sudanese civil conflicts. Sudanese refugees were evaluated with respect to symptoms of depression, post-traumatic stress disorder (PTSD) and social stress. Four respondents (22%) indicated that their interactions with the United Nations High Commissioner for Refugees (UNHCR) in Cairo, Egypt were the worst experiences since war-related atrocities. Fourteen participants (63.6%) felt 'extremely' betrayed by the UNHCR on a four point scale. Greater feelings of betrayal by the UNHCR were associated with greater avoidance and arousal symptoms of PTSD, symptoms of depression and trait anger. This is the first study of which we are aware that examines the relationship between sense of betrayal by the UNHCR and symptoms of PTSD, depression and anger among asylum seekers.

The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV-infected, respectively). Gene expression levels were quantified by quantitative RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.

Morphine may affect the properties of the blood-brain barrier (BBB) by modifying the expression of certain BBB markers. We have determined the effect of chronic morphine treatment on the expression and function of some BBB markers in the rat. The mRNAs of 19 selected genes encoding caveolins, endothelial transporters, receptors and tight junctions proteins in the total RNA of isolated cortex microvessels were assayed by quantitative RT-PCR (qRT-PCR). The expression of genes Mdr1a, Mrp1, Bcrp, Glut-1 and Occludin, was slightly increased, while that of Flk-1 was decreased in microvessels from morphine-treated rats. The expression of the Mrd1a and Mdr1b genes encoding the P-glycoprotein (P-gp) also increased in the whole hippocampus and cortex of morphine-treated rats. The Mdr1a gene induction (1.38-fold) observed by qRT-PCR was also confirmed using in situ hybridization technique (1.40-fold). Immunoblotting revealed an increase in P-gp expression in the hippocampus (1.8-fold) and cortex (1.36-fold) of morphine-treated rats, but no effect in isolated microvessels. In contrast, morphine treatment increased by 1.48-fold the expression of P-gp in a large vessel-enriched fraction. The integrity of the BBB, measured by in situ brain perfusion of [(14)C]-sucrose, and the activity of P-gp at the BBB, measured with the P-gp substrate [(3)H]-colchicine, were not modified by morphine. Immunohistofluorescence experiments revealed that P-gp expression is restricted to large vessels and microvessels in control rats and that morphine treatment did not induce the expression of P-gp in the brain parenchyma (astrocytes or neurons). Taken together, our results showed that chronic morphine treatment does not significantly alter BBB integrity or P-gp activity. The impact of morphine-mediated P-gp induction observed in large vessels remains to be determined in terms of brain disposition of drugs that are P-gp substrates.

Imatinib (Glivec, Gleevec, STI571) is a small tyrosine kinase inhibitor that is currently in phase II clinical trials in patients with recurrent glioblastoma. Its therapeutic benefit is minimal, although it is greater in some patients when combined with hydroxyurea. Imatinib is transported by human and rodent ATP-binding cassette (ABC) transporters like P-glycoprotein (Pgp) and the breast cancer resistance protein (BCRP). We have investigated whether ABC transporters determine the pharmacokinetics of imatinib and its pharmacological active metabolite CGP74588 in rat C6 glioma cells. ABC transporter expressions were measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). C6 cells express high concentrations of the Pgp-encoding gene Mdr1b and a 10-fold smaller amount of the Pgp-encoding gene Mdr1a. The relative expression of ABC transporter genes are: Mdr1b>Mrp4>Mrp1>Mrp5>Mdr1a>Mrp3>Mrp2>Bcrp. The accumulation of imatinib into C6 cells increased linearly with the extracellular concentration of imatinib (0.5-50microM) and was not increased by zosuquidar (selective Pgp inhibitor) or elacridar (inhibitor of both Pgp and Bcrp). In contrast, there was less CGP74588 than imatinib in C6 cells and its concentration increased with the extracellular concentration in a sigmoid fashion. Lastly, 10microM valspodar (selective Pgp inhibitor), elacridar and zosuquidar all increased the accumulation of CGP74588 by 2.5-fold. Thus CGP74588 is readily transported by the Pgp in rat C6 gliomas cells, which raises the question of the role of Pgp in the resistance of recurrent glioblastomas to imatinib.

The electronic absorption spectra of 2-(2-hydroxynaphthylazo)-4-hydroxy-6-methyl-1,3-pyrimidine in pure organic solvents of different polarities and in buffer solutions of varying pH are studied. The important bands in the IR and the main signals in the (1)H NMR spectra are assigned. The observed UV-vis absorption bands are assigned to the corresponding electronic transitions. The molecular stoichiometry, stability constant, absorption maximum, molar absorptivity and Sandell's sensitivity of the complexes are calculated. Obeyence to Beer's law and Ringbom optimum concentration ranges are also determined. The ability of using the titled azodye as metalochromic indicator in complexometric titrations was also studied. The effect of Co(II), Ni(II) and Cu(II) ions on the fluorescence of the azodye is also considered. The solid Cu(II) complexes of the titled azodye have been prepared and characterized by elemental, IR, UV-vis spectra as well as by conductometric and magnetic measurements. The data suggest square planar geometry for 1:1 and 1:2 (M:L) complexes. The thermal behaviour of the complexes has been studied. The kinetic parameters (n, E, A, deltaH, DeltaS and deltaG) of the thermal decomposition steps are computed using Coats-Redfern equations.

Physiological studies of the blood-brain barrier (BBB) are often performed in rats. We describe the functional characterization of a reproducible in vitro model of the rat BBB and its validation for investigating mechanisms involved in BBB regulation. Puromycin-purified primary cultures of brain endothelial cells, co-cultured with astrocytes in the presence of hydrocortisone (HC) and cAMP, presented low sucrose permeability (< or =0.1 x 10(-3) cm/min) and high transendothelial electrical resistance (> or =270 Omega cm(2)). Expression of specific BBB markers and their transcripts was detected by immunostaining and RT-PCR, respectively: tight junction proteins (claudin-3 and -5, ZO-1 and occludin) and transporters (P-gp, Bcrp and Oatp-2). RT-PCR experiments demonstrated a role of treatment by astrocytes, HC and cAMP in regulation of the transcript level of tight junction proteins (claudin-5 and ZO-1) as well as transporters (Mdr1a, Mrp3, Mrp4, Bcrp, Glut-1), while transcript level of Mdr1b was significantly decreased. The functionality of efflux pumps (P-gp, Mrps and Bcrp) was demonstrated in the presence of specific inhibitors (PSC833, MK571 or Ko143, respectively) by (i) assessing the uptake of the common substrates rhodamine 123 and daunorubicin and (ii) evaluating apical to basolateral and basolateral to apical polarized transport of daunorubicin. In addition, a good correlation (R=0.94) was obtained between the permeability coefficients of a series of compounds of various lipophilicity and their corresponding in vivo rodent blood-brain transfer coefficients. Taken together, our results provide compelling evidence that puromycin-purified rat brain endothelial cells constitute a reliable model of the rat BBB for physiological and pharmacological characterization of BBB transporters.

Quantitative RT-PCR (qRT-PCR) and Western blotting studies on transporters at the blood-brain barrier (BBB) of isolated brain microvessels have produced conflicting data on their cellular distribution. A major problem is identifying cells expressing the genes of interest, since isolated brain microvessels are composed of several cell types and may be contaminated with mRNA or proteins from astrocytes and neurons. We isolated rat brain microvessels and examined microscopically samples at each step of isolation to evaluate microvessel purity. The expression of specific markers of endothelial cells (Glut-1, Flk-1), pericytes (Ng2), neurons (synaptophysin, Syn) and astrocytes (Gfap) was measured by qRT-PCR in order to select the protocol giving the least astrocyte and neuron mRNAs and the most endothelial mRNAs. We also evaluated the gene expression of drug transporters (Mdr1a, Mdr1b, Mrp1-5, Bcrp and Oatp-2) at each step to optimize their location in cells at the BBB. The Mdr1a, Mrp4, Bcrp and Oatp-2 gene profiles were similar to those of endothelium markers. The profiles of Mrp2 and Mrp3 closely resembled that of Ng2. Mrp5 and Mrp1 expression was not increased in the microvessel-enriched fraction, suggesting that they are ubiquitously expressed throughout the cortex parenchyma. We also evaluated by Western blotting the expression of P-gp, Mrp2, Gfap and Syn in the cortex and in the purest obtained microvessel fraction. Our results showed that P-gp expression strongly increased in microvessels whereas Mrp2 was not detected in any of the fraction. Surprisingly, Gfap expression increased in isolated microvessels whereas Syn was not detected. Our results showed that the strategy consisting of identifying gene expression at different steps of the protocol is useful to identify cells containing mRNA at the BBB and give overall similar results with protein expression.

Epidemiology and pathogenesis in urinary stones diagnosed in 184 patients were studied. Mean age was 38.3 years. Male to female ratio was 2.5:1. Stones were predominantly of mixed type: calcium oxalate was the commonest compound. Anatomical distribution of urinary stones was 67.4% renal, 12.5% ureteric and 14.6% bladder. Recurrence rate following previous surgical removal was 15.0%. Bacteria were isolated from 19 (24.4%) of 78 urinary stones: 14 were urea splitting and 5 non-urea splitting. Females had a greater chance of having infected stones. All bacteria isolated were sensitive to gentamicin and nalidixic acid. All isolates were resistant to amoxicillin and erythromycin. Multiple resistance to 6 antimicrobial agents was common (58.8%).

Objectives: The negative effects of cigarette smoking on oral health are well established, yet few studies assessed patient awareness of such effects. The aim of this study was to examine differences in dental patient knowledge and awareness of the effects of smoking on oral health between smokers and non-smokers., Methods: Adult patients from 12 dental centers in Kuwait were asked to complete a 14-point self-administered structured questionnaire on the effects of smoking on oral health in this cross-sectional survey. Significant associations between oral health knowledge, smoking status, and sociodemographic variables were examined with univariate analysis and logistic regression., Results: A total of 1012 subjects participated (response rate = 84.3%). The prevalence of smoking was 29.3%. Fewer smokers than non-smokers thought that oral health and smoking are related (92.2% vs. 95.8%; P = 0.020), and that smoking affected oral cancer (52.4% vs. 66.8%; P < 0.001), periodontal health (72% vs. 78%; P = 0.040), or tooth staining (86.1% vs. 90.9%; P = 0.018). Logistic regression analysis showed smokers to be significantly less aware of the oral health effects of smoking than non-smoking patients (OR=1.51; 95% CI: 1.05-2.16; P = 0.025)., Conclusion: Smoking dental patients are significantly less aware of the oral health effects of smoking than non-smokers. Comparative studies in other populations may be warranted to ascertain the validity of these results.

The medical records of 122 patients with meningitis admitted during one year reviewed. Cerebrospinal fluid (CSF) culture confirmed bacterial meningitis in 59; of the remaining 63, 35 were partially treated bacterial, 25 were viral, and three were tuberculous meningitis. Eighty-two patients (65%) were Saudi and most were younger than 5 years. Hemophilus influenzae was the most common pathogen isolated in patients younger than one year, and Neisseria meningiditis was the most common organism identified overall, especially in cases occurring during the Haj. CSF culture and the latex agglutation test were the most reliable in confirming diagnosis.

Deletions of the ponA and ponB genes of Escherichia coli have been constructed in vitro and recombined into the chromosome to produce strains that completely lack penicillin-binding protein 1A or penicillin-binding protein 1B. In each case a DNA fragment internal to the gene was replaced by a fragment encoding an antibiotic resistance. The ponA and ponB deletions can therefore be readily introduced into other E. coli strains by P1 transduction of the antibiotic resistance. Although the complete absence of penicillin-binding protein 1A or penicillin-binding protein 1B was tolerated, the absence of both of these proteins was shown to result in bacterial lysis.

Penicillin-binding proteins 1A and 1B of Escherichia coli are the major peptidoglycan transglycosylase-transpeptidases that catalyse the polymerisation and insertion of peptidoglycan precursors into the bacterial cell wall during cell elongation. The nucleotide sequence of a 2764-base-pair fragment of DNA that contained the ponA gene, encoding penicillin-binding protein 1A, was determined. The sequence predicted that penicillin-binding protein 1A had a relative molecular mass of 93 500 (850 amino acids). The amino-terminus of the protein had the features of a signal peptide but it is not known if this peptide is removed during insertion of the protein into the cytoplasmic membrane. The nucleotide sequence of a 2758-base-pair fragment of DNA that contained the ponB gene, encoding penicillin-binding protein 1B, was also determined. Penicillin-binding protein 1B consists of two major components which were shown to result from the use of alternative sites for the initiation of translation. The large and small forms of penicillin-binding protein 1B were predicted to have relative molecular masses of 94 100 and 88 800 (844 and 799 amino acids). The amino acid sequences of penicillin-binding proteins 1A and 1B could be aligned if two large gaps were introduced into the latter sequence and the two proteins then showed about 30% identity. The amino acid sequences of the proteins showed no extensive similarity to the sequences of penicillin-binding proteins 3 or 5, or to the class A or class C beta-lactamases. Two short regions of amino acid similarity were, however, found between penicillin-binding proteins 1A and 1B and the other penicillin-binding proteins and beta-lactamases. One of these included the predicted active-site serine residue which was located towards the middle of the sequences of penicillin-binding proteins 1A, 1B and 3, within the conserved sequence Gly-Ser-Xaa-Xaa-Lys-Pro. The other region was 19-40 residues to the amino-terminal side of the active-site serine and may be part of a conserved penicillin-binding site in these proteins.