Spina bifida

Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60-70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa

Sport psychology in an Olympic swimming team: Perceptions of the management and coaches

It has been over 20 years since research has been published on perceptions of sport psychology services in Olympic sport, and this work spanned multiple sports, had a North American focus, and did not report management’s views. In this study, we resurrect this line of inquiry through the investigation of management and coaches’ perceptions of sport psychology in a European Olympic swimming team. Following semistructured interviews with 12 members of the management and coaching staff, we identified themes relating to retrospective reflections of past psychology-related services (i.e., negative previous experiences, lack of understanding, unease with service, threat to coach-swimmer relationship) and prospective projections of future psychology-related services (i.e., recognition of importance, scope of target client groups, roles with the coaches, confidentiality issues, practitioner characteristics). Within this team, sport psychology was perceived largely negatively, but despite this, the coaches and management recognized the importance and potential of the service. This apparent disparity can be explained by a range of factors, but the team culture, delivery method, and individual personalities appear to be particularly influential in this regard. To enhance the quality and receptivity of service provision, researchers and practitioners should effectively communicate with recipients of the service and consider not just what is delivered but by whom and how it is delivered

Olympic coaching excellence: A quantitative study of Olympic swimmers' perceptions of their coaches.

Although coaching is a co-created process, researchers investigating the psychological aspects of Olympic coaching have tended to overlook the perceptions of athletes and whether these distinguish between performance-related outcomes. The objective of this research was to examine whether athletes' perceptions of their coaches discriminate between world-leading (i.e., Olympic gold medal winning) and world-class (i.e., Olympic non-gold medal winning) coaches. Observer-reported psychometric questionnaires were completed by 38 Olympic swimmers who had collectively won 59 Olympic medals, of which 31 were gold. The questionnaires assessed perceptions of 12 variables within the Big Five personality traits, the dark triad, and emotional intelligence, and the data was analyzed using three one-way multivariate analysis of variance and follow-up univariate F-tests. The results showed that world-leading coaches were perceived to be significantly higher on conscientiousness, openness to experience, perception of emotion, and management of others emotion, and lower on narcissism, than world-class coaches. This suggests that athletes' perceptions of their coaches may discriminate between world-leading and world-class coaches. The implications for coaches' psychological development are discussed and compared with previously reported Olympic coaches' perceptions of themselves

The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98×10−4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10−6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs—rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)—showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development

Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis

Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure–response relationship is less clear. To clarify this relationship we conducted a review and meta-analysis of published reports of occupational epidemiologic studies. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 μg/m(3) years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11–1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15–1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21–72.78) and chimney sweeps (16.2; CI, 1.64–160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect. These results provide a more secure basis for risk assessment than was previously available

Cervical dysplasia and cancer and the use of hormonal contraceptives in Jamaican women

<p>Abstract</p> <p>Background</p> <p>This study was conducted to determine whether use of hormonal contraceptives is associated with cervical dysplasia and cancer in a population where there is widespread use of hormonal contraception and the rates of cervical cancer remain high at 27.5/100,000.</p> <p>Methods</p> <p>A case-control study was conducted among women visiting the colposcopy and gynaelogical clinics at a tertiary referral hospital. Two hundred and thirty six cases CIN I (72), II (59), III (54), cancer (51) and 102 controls, consented and were interviewed on use of contraceptives using a structured questionnaire. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of hormonal contraception in cases and controls and in low and high risk cases. Recruitment was carried out from 2001–2002.</p> <p>Results</p> <p>Contraceptives used were: oral contraceptives – 35%, injections (depot medroxy progesterone acetate (Depo-provera) – 10%, Intrauterine devices – 2%, combinations of these and tubal ligation – 30%. 23% reported use of 'other' methods, barrier contraceptives or no form of contraception. Barrier contraceptive use was not significantly different between cases and controls. Current and/or past exposure to hormonal contraceptives (HC) by use of the pill or injection, alone or in combination with other methods was significantly higher in the cases. In multivariate analysis with age and number of sexual partners as co-variates, use of hormonal contraception was associated both with disease, [OR, 1.92 (CI 1.11, 3.34; p = 0.02] and severity of the disease [OR, 2.22 (CI 1.05, 4.66) p = 0.036]. When parity and alcohol consumption were added to the model, hormonal contraception was no longer significant. The significant association with high risk disease was retained when the model was controlled for age and number of sexual partners. Depo-provera use (with age and number of sexual partners as covariates) was also associated with disease [OR, 2.43 (CI 1.39, 4.57), p = 0.006] and severity of disease [OR 2.51 (1.11, 5.64) p = 0.027]. With parity and alcohol added to this model, depo-provera use retained significance. Exposure to HC > 4 years conferred more risk for disease and severity of disease.</p> <p>Conclusion</p> <p>Hormonal contraception did confer some risk of dysplasia and women using HC should therefore be encouraged to do regular Pap smear screening.</p

Primary liposarcoma of the ascending colon: a rare case of mixed type presenting as hemoperitoneum combined with other type of retroperitoneal liposarcoma

<p>Abstract</p> <p>Background</p> <p>Liposarcoma occurs most commonly in the extremities and retroperitoneum, however, it has been rarely observed in the colon.</p> <p>Case Presentation</p> <p>A case is reported a 41-year-old man with liposarcoma of ascending colon which was presented as hemoperitoneum and combined with a different histological type of retroperitoneal liposarcoma. He visited hospital with right lower abdominal pain and palpable mass. Laboratory data including tumor markers were within normal limits, and computed tomography revealed a 15 × 10 cm sized enhancing soft mass. Right hemicolectomy was performed, and after that, a further large retroperitoneal mass was revealed and this was also radically excised. Mixed-type colon liposarcoma and well differentiated type of retroperitoneal liposarcoma were diagnosed in pathologic report. The patient has remained free of disease for 24 months.</p> <p>Conclusions</p> <p>No standardized guidelines have been established for its treatment because too small a number of cases have been reported, but surgical resection was considered the treatment of choice.</p

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data