Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology.

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs

PREVALENCE OF ANTIBODIES AGAINST MYCOPLASMA MELEAGRIDIS IN BREEDING TURKEYS IN LIMA

Se determinó la prevalencia de anticuerpos a Mycoplasma meleagridis en 20 lotes de pavos reproductores del departamento de Lima durante el año 2007. Se tomaron 400 muestras de sangre de pavos machos y hembras, entre 8 y 57 semanas de edad, en los distritos de Asia y Chilca. Las muestras se analizaron mediante el ensayo de inmunoabsorción ligado a la enzima (ELISA) a fin de determinar la presencia de anticuerpos contra M. meleagridis. Se encontraron tres muestras positivas (una por lote), resultando una prevalencia de 0.75 ± 0.04%. La seropositividad por lote afectado fue de 5%, sin que se mostrasen signos clínicos compatibles con la enfermedad. Se concluye que los 20 lotes examinados no fueron expuestos al microorganismo y que estos resultados se deben a reacciones falsas positivas.A field study was conducted to determine the prevalence of antibodies againstMycoplasma meleagridis in 20 turkey breeder flocks located in the Lima region during2007. A total of 400 blood samples were taken from male and female birds of 8 to 57 weeksold, from Asia and Chilca districts. The indirect enzyme linked immunosorbent assay(ELISA) was used to measure serum antibodies against M. meleagridis. Three positivesamples were found (one per flock) representing a prevalence of 0.75 ± 0.04%. Theseropositive reactivity per affected flock was 5%, and without showing clinical signscompatible to those observed in the disease. According to these findings, it is concluded that the 20 flocks were not exposed to M. meleagridis and that the positive results maybe due to false positive seroreactions

Influence of production variables and starting material on charcoal stable isotopic and molecular characteristics

We present a systematic study on the effect of starting species, gas composition, temperature, particle size and duration of heating upon the molecular and stable isotope composition of high density (mangrove) and low density (pine) wood. In both pine and mangrove, charcoal was depleted in o13C relative to the starting wood by up to 1.6% and 0.8%, respectively. This is attributed predominantly to the progressive loss of isotopically heavier polysaccharides, and kinetic effects of aromatization during heating. However, the pattern of o13C change was dependant upon both starting species and atmosphere, with different structural changes associated with charcoal production from each wood type elucidated by Solid-State o13C Nuclear Magnetic Resonance Spectroscopy. These are particularly evident at lower temperatures, where variation in the oxygen content of the production atmosphere results in differences in the thermal degradation of cellulose and lignin. It is concluded that production of charcoal from separate species in identical conditions, or from a single sample exposed to different production variables, can result in significantly different o13C of the resulting material, relative to the initial wood. These results have implications for the use of charcoal isotope composition to infer past environmental change

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p, and that the combination of both events associates with a surprising decrease in survival rates (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p, rather than a consequence of global genome instability, and validates in HNSCC and pan-cancer cohorts. In Human Papilloma Virus positive (HPV+) tumors, in which HPV inactivates TP53, 3p deletion is also common and associates with poor outcomes. The TP53-3p event is modified by mir-548k expression which decreases survival even further, while it is mutually exclusive with mutations to RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease

Generic protease detection technology for monitoring periodontal disease

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.<br/

14C and 13C characteristics of higher plant biomarkers in Washington margin surface sediments

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 105 (2013): 14-30, doi:10.1016/j.gca.2012.11.034.Plant wax lipids and lignin phenols are the two most common classes of molecular markers that are used to trace vascular plant-derived OM in the marine environment. However, their 13C and 14C compositions have not been directly compared, which can be used to constrain the flux and attenuation of terrestrial carbon in marine environment. In this study, we describe a revised method of isolating individual lignin phenols from complex sedimentary matrices for 14C analysis using high pressure liquid chromatography (HPLC) and compare this approach to a method utilizing preparative capillary gas chromatography (PCGC). We then examine in detail the 13C and 14C compositions of plant wax lipids and lignin phenols in sediments from the inner and mid shelf of the Washington margin that are influenced by discharge of the Columbia River. Plant wax lipids (including n-alkanes, n-alkanoic (fatty) acids, n-alkanols, and n-aldehydes) displayed significant variability in both δ13C (-28.3 to -37.5 ‰) and ∆14C values (-204 to +2 ‰), suggesting varied inputs and/or continental storage and transport histories. In contrast, lignin phenols exhibited similar δ13C values (between -30 to -34 ‰) and a relatively narrow range of ∆14C values (-45 to -150 ‰; HPLC-based mesurement) that were similar to, or younger than, bulk OM (-195 to -137 ‰). Moreover, lignin phenol 14C age correlated with the degradation characteristics of this terrestrial biopolymer in that vanillyl phenols were on average ~500 years older than syringyl and cinnamyl phenols that degrade faster in soils and sediments. The isotopic characteristics, abundance, and distribution of lignin phenols in sediments suggest that they serve as promising tracers of recently biosynthesized terrestrial OM during supply to, and dispersal within the marine environment. Lignin phenol 14C measurements may also provide useful constraints on the vascular plant end member in isotopic mixing models for carbon source apportionment, and for interpretation of sedimentary records of past vegetation dynamics. Key words: 14C and 13C composition, radiocarbon age, plant wax lipids, lignin phenols, Washington margin, marine carbon cycling, terrestrial organic matterGrants OCE-9907129, OCE-0137005, and OCE-0526268 (to TIE) from the National Science Foundation (NSF) supported this research

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. Methods: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and &gt; 10&nbsp;years of practice experience, with only 2 case exceptions noted. Conclusion: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe