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BackgroundThe discovery of coding variants in genes that confer risk of intellectual disability (ID) is an important step toward understanding the pathophysiology of this common developmental disability.MethodsHomozygosity mapping, whole-exome sequencing, and cosegregation analyses were used to identify gene variants responsible for syndromic ID with autistic features in two independent consanguineous families from the Arabian Peninsula. For in vivo functional studies of the implicated gene’s function in cognition, Drosophila melanogaster and mice with targeted interference of the orthologous gene were used. Behavioral, electrophysiological, and structural magnetic resonance imaging analyses were conducted for phenotypic testing.ResultsHomozygous premature termination codons in PDZD8, encoding an endoplasmic reticulum–anchored lipid transfer protein, showed cosegregation with syndromic ID in both families. Drosophila melanogaster with knockdown of the PDZD8 ortholog exhibited impaired long-term courtship-based memory. Mice homozygous for a premature termination codon in Pdzd8 exhibited brain structural, hippocampal spatial memory, and synaptic plasticity deficits.ConclusionsThese data demonstrate the involvement of homozygous loss-of-function mutations in PDZD8 in a neurodevelopmental cognitive disorder. Model organisms with manipulation of the orthologous gene replicate aspects of the human phenotype and suggest plausible pathophysiological mechanisms centered on disrupted brain development and synaptic function. These findings are thus consistent with accruing evidence that synaptic defects are a common denominator of ID and other neurodevelopmental conditions.

“Chiari zero malformation” is a rare and a relatively new described condition which associates syringohydromyelia without caudal displacement of the cerebellar tonsils through the foramen magnum. We present a case of a 40 years old woman with Chiari zero malformation with both syringomyelia and syringobulbia and a good clinical and radiological outcome after posterior fossa decompression. The presence of associated syringomyelia and syringobulbia in this condition is less frequent and it usually occurs in younger patients. In our case we considered syringobulbia as being an extension of syringomyelia.

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33.

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33.

Clinical History Image Findings Discussion Find Diagnosis Differential Diagnosis, male, 56 years, Clinical History: 56 year old male patient presented with partial seizures and progressive onset of focal neurological deficits over the last 8 months. No relevant past medical history. Final Diagnosis: Diffuse Astrocytoma NOS with protoplasmic pattern.

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33.

Background: Rectal cancer management has as its main component the surgical treatment. The purpose of the paper is to point out the advantages and disadvantages of sphincter saving techniques, respecting the oncological principles. Material and method: A cross-sectional, retrospective study was performed on a group of 69 patients admitted and surgically treated for rectal cancers in the Surgical Clinic I of the County Emergency Clinical Hospital of Tîrgu Mureș, for a period of one year (April 2012 - April 2013) and to whom rectal resections were performed. We followed the immediate postoperative evolutions in these patients, making a comparative analysis between those with the sphincter saving surgery and those in which other operations were performed. Results: From the total of 69 patients diagnosed with rectal cancer, sphincter saving procedures with restoration of digestive continuity by coloanal anastomosis were performed in 12 patients (17.39%) using the peranal or transanal approach; in 42 patients (60.86%) anterior rectosigmoidian resections with low and very low colorectal anastomosis („very low” Dixon procedure) were performed. In 15 cases (21.74%) the Miles type of rectal resections, using the abdomino-perineal way, were performed. Out of the 12 cases with peranal or transanal anastomosis, 4 cases had postoperative complications. Conclusions: Rectal resection procedures, which are restoring the digestive tract continuity using low anastomosis (colorectal, coloanal, peranal or transanal), are representing viable and „physiological” alternatives, if they respect the oncologic principles. In well selected cases, the immediate postoperative evolution is favorable, relieving the patient from the psychological and physical trauma due to the presence of a colostomy

Daunorubicin has historically been considered the anthracycline of choice at many cancer centers for the treatment of acute myeloid leukemia (AML). Drug shortages have required the substitution of daunorubicin with idarubicin. Randomized studies have shown idarubicin (10-12mg/m(2)) to be comparable or superior to standard dose daunorubicin (45-60mg/m(2)) for achieving complete remission (CR). Whether these results can be extrapolated to dose-intense daunorubicin (90mg/m(2)), recently shown to improve CR rates when compared to standard daunorubicin doses remains uncertain. This observational study was conducted at Northwestern Memorial Hospital (NMH) to compare CR rates. The results suggest idarubicin is equivalent to daunorubicin, and for some subsets of patients, idarubicin may have superior CR rates.

For a correct design of supercritical water-cooled reactor (SCWR) components, data regarding the behavior of candidate materials in supercritical water are necessary. Corrosion has been identified as a critical problem because the high temperature and the oxidative nature of supercritical water may accelerate the corrosion kinetics. The goal of this paper is to investigate the oxidation behavior of Incoloy 800 exposed in autoclaves under supercritical water conditions for up to 1440 h. The exposure conditions (thermal deaerated water, temperatures of 723, 773, 823 and 873 K and a pressure of 25 MPa) have been selected as relevant for a supercritical power plant concept. To investigate the structural changes of the oxide films, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX) and electrochemical impedance spectroscopy (EIS) analyses were used. Results show changes in the oxides chemical composition, microstructure and thickness versus testing conditions (pressure, temperature and time). The oxide films are composed of two layers: an outer layer enriched in Fe oxide and an inner layer enriched in Cr and Ni oxides corresponding to small cavities supposedly due to internal oxidation.

The composition of the copolymers of 1,3-dioxolane with 1,3-dioxepane was investigated using FT-IR and DSC. The first method produce accurate values for the overall composition, the later allows discriminating between the copolymer and the mixture of homopolymers.

A BF3 complex has been grafted onto silica and used as initiator to polymerize 1,3-dioxolane and 1,3-dioxepane. Grafting the active centers leads to a decrease of the reaction rate. The molecular weight increases steadily, parallel to the monomer conversion and the polydispersity is rapidly stabilized at a low value. MALDI-TOF mass spectrometry analysis shows that most of the polymer chains are initiated by a proton and lost a CH2O unit. An exchange process between polymer chains bound to the silica and those remaining in the reactional medium was proposed. Finally, a semi-continuous process was investigated by adding continuously dioxolane during a 100 hours period.

Photocationic polymerization for three cyclic acetals, namely 1,3-dioxolane, 1,3-dioxepane and 1,3,6-trioxocane, respectively, has been studied. Several cationic photo-initiators (diaryliodonium or triarylsulfonium salts, and one arene-metal complex) have been used. Differential scanning photo-calorimetry (DPC) has been employed to record the dependence conversion versus time. DPC thermogrames, in turn, have been utilized to calculate the propagation reaction constants as well as the corresponding activation energies. The values for the propagation constants at 30°C are 1.6.10 2 L/mol.s for 1,3-dioxolane, using a diaryliodonium salt as photoinitiator, 1.6.10 3 L/mol.s for 1,3-dioxepane and 6.1.10 3 L/mol.s for 1,3,6-trioxocane, respectively, in the presence of a triarylsulfonium salt as photoinitiator. The activation energies are in the range of 9.6+19.6 kcal/mole.

Functionalised polycaprolactones have been obtained by anionic coordinated ring-opening polymerization with Al(OiPr) 3 as the initiator in the presence of monosaccharides as transfert agents. 1 H and 13 C NMR spectroscopy, as well as MALDI-TOF mass spectrometry clearly show the functionalisation of the polycaprolactone chains. Protected monosaccharides bearing primary hydroxyl groups are suited best to get well-controlled polymer chains. Polycaprolactones functionalised with galactopyranose end groups have been used for the preparation of nanoparticles according to the emulsification diffusion procedure. Nanospheres and nanocapsules with diameters around 0.50 μm could be obtained.

Evidence suggests that the completion of a work placement as part of an undergraduate degree is of positive benefit to both graduates and employers, particularly in an era that stresses the economic contribution of the United Kingdom in higher education through developing graduate employability (Wilton, 2012). This benefit is twofold: first, work placements positively contribute to the development of generic employability skills; and second, placements provide a ‘head start’ for graduates at the outset of their careers. Currently, there are 54 placement students / graduate interns employed at SHU. Although, it is acknowledged that these employees are employed like any other member of staff to perform a role, this category of employee is specifically engaged in developing their future employability, thus it is important to ascertain how these employees perceive their development. Semi-structured interviews were conducted to understand the perceptions of placement students, graduate interns and their line managers in collaboration with the Human Resources (HR) department, and data was analysed using thematic analysis. Findings revealed the following main themes: expectations; feelings; how the placement student / graduate intern worked; skills; personal development and working relationships; reflection on experience; thoughts about the placement student / graduate intern and views about their placement student / graduate intern. Within each main theme, various subthemes were also found. This research highlights aspects of the placement student and graduate intern experiences at SHU. Additionally, it can facilitate greater use of SHU as an employer in providing these types of opportunity in order to promote recruitment to these posts.

Dose-intense etoposide-cyclophosphamide (D-I ECy) without stem cell transplantation has been used in salvage regimens for the treatment of resistant acute myeloid leukemia(AML). Previous D-I ECy studies classified AML according to FAB-criteria, before cytogenetic risk was found to be a major determinant of prognosis. Currently the influence of karyotype on response to D-I ECy is unknown. Thus, an observational study was conducted in thirty four patients treated with D-I ECy for resistant AML. The results show this regimen is moderately effective in achieving CR in relapsed AML patients, including those with age >60 and poor cytogenetic risk category.

Evaluating teaching, learning and assessment methods at module-level is essential, particularly in enhancing academic quality. However, module evaluations are usually designed and conducted by the University to serve their own purpose of maintaining Academic standards and often do not consider student involvement in the process of module evaluation. In our project named Students as researchers, students were appointed as researchers to gather student perceptions on a large first year undergraduate (Level 4) research module for social science students. This is a compulsory module for Politics, Sociology and Criminology single and joint honours students. This module was recently revalidated and incorporated an applied approach towards teaching research methods after feedback from previous years. \ud The research has taken a mixed-methods approach. This encompassed an online survey questionnaire that has been distributed to all 467 first-year students on the module. To accompany this quantitative data, interviews were organized for richer, in-depth data to inform positive change on the development of the module. \ud The findings of this work have fed into further development of this module for future cohorts. This evaluation has offered teaching staff an opportunity to reflect on our research findings and their own academic practice both within the department and within other disciplinary areas. It has also offered students an opportunity to feedback on their own student experience at module level and in doing so to enhance the quality of teaching and assessment of the module for future cohorts. It has additionally allowed student-researchers to gain knowledge of the practicalities of action research methodology and evaluation research through taking part in the project.