Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Long-term all-sites cancer mortality time trends in Ohio, USA, 1970–2001: differences by race, gender and age

BACKGROUND: There were significant changes in cancer mortality in the USA over the last several decades, in the whole country and in particular states. However, no in depth analysis has been published so far, dealing with changes in mortality time trends in the state of Ohio. Since the state of Ohio belongs to the states of relatively high level of all-sites mortality in both males and females, it is of interest to analyze recent changes in mortality rates, as well as to compare them with the situation in the rest of the USA. The main aim of this study was to analyze, describe and interpret all-sites cancer mortality time trends in the population of the State of Ohio. METHODS: Cancer mortality data by age, sex, race and year for the period 1970–2001 were obtained from the Surveillance Research Program of the National Cancer Institute SEER*Stat software. A joinpoint regression methodology was used to provide estimated annual percentage changes (EAPCs) and to detect points in time where significant changes in the trends occurred. RESULTS: In both, males and females mortality rates were higher in blacks compared with whites. The difference was bigger in males (39.9%) than in women (23.3%). Mortality rates in Ohio are generally higher than average USA rates – an overall difference was 7.5% in men in 1997–2001, and 6.1% in women. All-sites mortality trends in Ohio and in the whole USA are similar. However, in general, mortality rates in Ohio remained elevated compared with the USA rates throughout the entire analyzed period. The exceptions are the rates in young and middle-aged African Americans. CONCLUSION: Although direction of time trends in Ohio are similar in Ohio and the whole US, Ohio still have cancer mortality rates higher than the US average. In addition, there is a significant discrepancy between white and black population of Ohio in all-sites mortality level, with disadvantage for Blacks. To diminish disparities in cancer mortality between African Americans and white inhabitants of Ohio efforts should be focused on increasing knowledge of black people regarding healthy lifestyle and behavioral risk factors, but also on diminishing socioeconomic differences, and last but not least, on better access to medical care

Translation initiation and its deregulation during tumorigenesis

Regulation of protein synthesis at the level of translation initiation is fundamentally important for the control of cell proliferation under normal physiological conditions. Conversely, misregulation of protein synthesis is emerging as a major contributory factor in cancer development. Most bulk protein synthesis is initiated via recognition of the mRNA 5′ cap and subsequent recognition of the initiator AUG codon by a directional scanning mechanism. However, several key regulators of tumour development are translated by a cap-independent pathway. Here we review eukaryotic translation initiation, its regulation and the ways in which this regulation can break down during tumorigenesis

Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing

Epidemiological studies show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer incidence. We measured the rate ratio for colorectal adenocarcinoma according to dosage and the timing of exposure by means of a case–control study, nested in a non-concurrent cohort linkage study, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the source population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, calculated over successive time periods, characterized NSAID exposure. We accrued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon cancer a significant trend towards a decreasing rate ratio was associated with increasing exposure during the 6 months preceding diagnosis (P-trend = 0.002). For both cancers, significant trends were associated with exposure 11–15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.0001). At the highest exposure levels the rate ratio for colon cancer was 0.57 (95% confidence interval (CI) 0.36–0.89); for rectal cancer it was 0.26 (95% CI 0.11–0.61). No protection was associated with exposure during other periods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before any preventive effect will appear. © 1999 Cancer Research Campaig

Endoscopic and Percutaneous Preoperative Biliary Drainage in Patients with Suspected Hilar Cholangiocarcinoma

INTRODUCTION: Controversy exists over the preferred technique of preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCCA) requiring major liver resection. The current study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) in patients with resectable HCCA. METHODS: One hundred fifteen consecutive patients were explored for HCCA between 2001 and July 2008 and assigned by initial PBD procedure to either EBD or PTBD. RESULTS: Of these patients, 101 (88%) underwent PBD; 90 patients underwent EBD as primary procedure, and 11 PTBD. The technical success rate of initial drainage was 81% in the EBD versus 100% in the PTBD group (P = 0.20). Stent dislocation was similar in the EBD and PTBD groups (23% vs. 20%, P = 0.70). Infectious complications were significantly more common in the endoscopic group (48% vs. 9%, P < 0.05). Patients in the EBD group underwent more drainage procedures (2.8 vs. 1.4, P < 0.01) and had a significantly longer drainage period until laparotomy (mean 15 weeks vs. 11 weeks in the PTBD group; P < 0.05). In 30 patients, EBD was converted to PTBD due to failure of the endoscopic approach. CONCLUSIONS: Preoperative percutaneous drainage could outperform endoscopic stent placement in patients with resectable HCCA, showing fewer infectious complications, using less procedure

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

The development of instruments to measure the work disability assessment behaviour of insurance physicians

<p>Abstract</p> <p>Background</p> <p>Variation in assessments is a universal given, and work disability assessments by insurance physicians are no exception. Little is known about the considerations and views of insurance physicians that may partly explain such variation. On the basis of the Attitude - Social norm - self Efficacy (ASE) model, we have developed measurement instruments for assessment behaviour and its determinants.</p> <p>Methods</p> <p>Based on theory and interviews with insurance physicians the questionnaire included blocks of items concerning background variables, intentions, attitudes, social norms, self-efficacy, knowledge, barriers and behaviour of the insurance physicians in relation to work disability assessment issues. The responses of 231 insurance physicians were suitable for further analysis. Factor analysis and reliability analysis were used to form scale variables and homogeneity analysis was used to form dimension variables. Thus, we included 169 of the 177 original items.</p> <p>Results</p> <p>Factor analysis and reliability analysis yielded 29 scales with sufficient reliability. Homogeneity analysis yielded 19 dimensions. Scales and dimensions fitted with the concepts of the ASE model. We slightly modified the ASE model by dividing behaviour into two blocks: behaviour that reflects the assessment process and behaviour that reflects assessment behaviour.</p> <p>The picture that emerged from the descriptive results was of a group of physicians who were motivated in their job and positive about the Dutch social security system in general. However, only half of them had a positive opinion about the Dutch Work and Income (Capacity for Work) Act (WIA). They also reported serious barriers, the most common of which was work pressure. Finally, 73% of the insurance physicians described the majority of their cases as 'difficult'.</p> <p>Conclusions</p> <p>The scales and dimensions developed appear to be valid and offer a promising basis for future research. The results suggest that the underlying ASE model, in modified form, is suitable for describing the assessment behaviour of insurance physicians and the determinants of this behaviour. The next step in this line of research should be to validate the model using structural equation modelling. Finally, the predictive value should be tested in relation to outcome measurements of work disability assessments.</p

Distortion Isomerism of Cu(II) Chloride Adducts with Bis(2-benzimidazolyl)ethane. Synthesis, Characterization, X-ray Structures and Spectroscopy of Four Different Isomers

Metals in Catalysis, Biomimetics & Inorganic Material

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

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