Developmental abnormalities of mid and hindbrain: A study of 23 Egyptian patients

Introduction: With the advent of neuroimaging modalities specifically, magnetic resonance imaging (MRI), recognition of developmental defects of posterior fossa has greatly improved. The Aim: Is to delineate the clinical, cytogenetics and radiological features of patients with mid-hindbrain anomalies. Patient and Methods: Twenty-three patients with mid-hind brain malformations were included in this study. Complete clinical evaluation, cytogenetic analysis and neuroradiological study were done for each patient. Patients\' sex ratio was (M: F/ 0.9:1) and the mean age was 2.17 years. Parental consanguinity was 86.9 % and positive family history was recorded in 7 families. Based on clinico-radiological findings, patients were categorized as Joubert syndrome and related cerebellar disorders (34.8%), pontocerebellar hypoplasia (26.1%), lissencephaly cerebellar hypoplasia (13%), isolated cobblestone lissencephaly with normal muscle and eye (8.7%), isolated vermian hypoplasia (13%) and retrocerebellar cyst (4.4%). Results: Cytogenetic analysis revealed abnormalities in 3 patients (13%); pericentric inversion of chromosome 8 in a patient with lissencephaly cerebellar hypoplasia, del 5p14.3-pter delineating Cri du chat syndrome and associated with vermian hypoplasia and del 18q21.1-qter in a patient with retrocerebellar cyst due to paternal balanced translocation t (4;18). FISH for specific locus and whole chromosomal painting were used to document the assigned aberrations. Although most of the cerebellar malformations are of Mendelian inheritance, this study emphasizes the importance of chromosomal analysis for patients with posterior fossa anomalies. With more researches describing clinico-radiological characterization of hind brain dysgenesis will allow better understanding of these disorders, further delineation of relevant syndromes and new genes identification. Keywords: Cerebellar, hindbrain, joubert syndrome, cobblestone lissencephalypontocerebellar hypoplasia, cri du chat syndrome- del 18q21.1-qterEgyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 215-23

Spike sorting for large, dense electrode arrays

Developments in microfabrication technology have enabled the production of neural electrode arrays with hundreds of closely spaced recording sites, and electrodes with thousands of sites are under development. These probes in principle allow the simultaneous recording of very large numbers of neurons. However, use of this technology requires the development of techniques for decoding the spike times of the recorded neurons from the raw data captured from the probes. Here we present a set of tools to solve this problem, implemented in a suite of practical, user-friendly, open-source software. We validate these methods on data from the cortex, hippocampus and thalamus of rat, mouse, macaque and marmoset, demonstrating error rates as low as 5%

Clinical, anthropometric, radiological and molecular characteristics of Egyptian achondroplasia patients

Background: Achondroplasia is the most common form of non lethal skeletal dysplasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fi broblast growth factor receptor-3 (FGFR3) gene. Aim of the Work: Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample.Subjects and Methods: From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplifi cation technique. Results: Nineteen cases were sporadic (95%) and one case had an affected father (5%). A paternal age above 35 years at the time of child’s birth was present in 7 cases (35%). Paternal exposure to occupational heat was noted in 6 cases (30%) and parental exposure to chemicals in 3 cases (15%). All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometricmeasurements quantitatively confi rmed the body physique in thestudied cases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases (83%) with the G to A transition at nucleotide 1138 in 14 cases (77%). Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversio nmutation at nucleotide 1138 (5%).Conclusions: Awareness of the cardinal features of achondroplasia, properanthropometric measurements and detailed skeletal survey are the key foraccurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defi ned in patients with achondroplasia from other countries.Keywords: Achondroplasia, fi broblast growth factor receptor3,skeletal dysplasia, paternal heat exposure

Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors.

There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT

A Novel Inhalable Dry Powder to Trigger Delivery of Voriconazole for Effective Management of Pulmonary Aspergillosis

Invasive pulmonary aspergillosis (IPA) is a fatal fungal infection with a high mortality rate. Voriconazole (VCZ) is considered a first-line therapy for IPA and shows efficacy in patients for whom other antifungal treatments have been unsuccessful. The objective of this study was to develop a high-potency VCZ-loaded liposomal system in the form of a dry-powder inhaler (DPI) using the spray-drying technique to convert liposomes into a nanocomposite microparticle (NCMP) DPI, formulated using a thin-film hydration technique. The physicochemical properties, including size, morphology, entrapment efficiency, and loading efficiency, of the formulated liposomes were evaluated. The NCMPs were then examined to determine their drug content, production yield, and aerodynamic size. The L3NCMP was formulated using a 1:1 lipid/L-leucine ratio and was selected for in vitro studies of cell viability, antifungal activity, and stability. These formulated inhalable particles offer a promising approach to the effective management of IPA

Natural coagulates for wastewater treatment; a review for application and mechanism

The increase of water demand and wastewater generation is among the global concerns in the world. The less effective management of water sources leads to serious consequences, the direct disposal of untreated wastewater is associated with the environmental pollution, elimination of aquatic life and the spread of deadly epidemics. The flocculation process is one of the most important stages in water and wastewater treatment plants, wherein this phase the plankton, colloidal particles, and pollutants are precipitated and removed. Two major types of coagulants are used in the flocculation process included the chemical and natural coagulants. Many studies have been performed to optimize the flocculation process while most of these studies have confirmed the hazardous effects of chemical coagulants utilization on the ecosystem. This chapter reviews a summary of the coagulation/flocculation processes using natural coagulants as well as reviews one of the most effective natural methods of water and wastewater treatment

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BACKGROUND: Terminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats. METHODS: The blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test. RESULTS: The chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated. CONCLUSION: The present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects

Geriatric patients' expectations of their physicians: findings from a tertiary care hospital in Pakistan

<p>Abstract</p> <p>Background</p> <p>Geriatric health is a neglected and under-explored area internationally and in Pakistan. We aimed to ascertain the expectations of the geriatric patients from their physicians and the factors associated with patient satisfaction in this particular age bracket.</p> <p>Methods</p> <p>A cross-sectional survey was carried out at a tertiary care teaching hospital in Karachi, Pakistan. Data collection was carried out via face-to-face interviews based on structured, pre-tested questionnaires. All consenting individuals aged 65 years or above were recruited into the study. Convenience sampling was used to draw the sample. The data was analyzed using SPSS version 16. Geriatric patient's expectations from physicians were elicited using a set of 11 questions that were graded on a scale of 1-3 where 1 = not important, 2 = important, 3 = very important.</p> <p>Results</p> <p>Three hundred and eighty geriatric patients were interviewed. The response rate of this study was 89.8%. The mean age of the respondents was 73.4 ± 6.8 years. Two hundred and forty eight respondents (65.3%) were female. Diabetes mellitus (53.7%), hypertension (59.5%), arthritis (40.5%) and renal disease (32.1%) were common ailments among geriatric patients. More than 50% of the patients were visiting their physicians once every two to three months. Discussing treatment options and letting patients make the final decision (79.2%), prescribing minimum possible medications (84.5%), physician's holistic knowledge about the spectrum of care issues for geriatric patients (79.2%), being given a realistic but optimistic picture of future health by physicians (85.5%) were ranked as very important expectations by patients from their physicians. Cumulative household income (p = 0.005), most important health complaint (p = 0.01) and frequency of experiencing health complaint (p < 0.001) emerged as independent predictors of the satisfaction of geriatric patients from care provided by physicians.</p> <p>Conclusion</p> <p>We have documented the expectations of the geriatric patients from their physicians in a developing country. Physicians belonging to all disciplines should keep these expectations in mind during clinical encounters with geriatric patients.</p

Coexistence of a colon carcinoma with two distinct renal cell carcinomas: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present the case of a patient with two tumors in his left kidney and a synchronous colon cancer. While coexisting tumors have been previously described in the same kidney or the kidney and other organs, or the colon and other organs, to the best of our knowledge no such concurrency of three primary tumors has been reported in the literature to date.</p> <p>Case presentation</p> <p>A 72-year-old man of Greek nationality presenting with pain in the right hypochondrium underwent a series of examinations that revealed gallstones, a tumor in the hepatic flexure of the colon and an additional tumor in the upper pole of the left kidney. He was subjected to a right hemicolectomy, left nephrectomy and cholecystectomy, and his postoperative course was uneventful. Histopathology examinations showed a mucinous colon adenocarcinoma, plus two tumors in the left kidney, a papillary renal cell carcinoma and a chromophobe renal cell carcinoma.</p> <p>Conclusion</p> <p>This case underlines the need to routinely scan patients pre-operatively in order to exclude coexisting tumors, especially asymptomatic renal tumors in patients with colorectal cancer, and additionally to screen concurrent tumors genetically in order to detect putative common genetic alterations.</p

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal