A scoring system for detection of macrosomia and prediction of shoulder dystocia: a disappointment.

OBJECTIVE: To develop a scoring system for the detection of a macrosomic fetus (birth weight (BW) >or= 4000 g) and predict shoulder dystocia among large for gestational age fetuses. STUDY DESIGN: We retrospectively identified all singletons with accurate gestational age (GA) that were large for GA (abdominal circumference (AC) or estimated fetal weight (EFW) >or= 90% for GA) at >or=37 weeks with delivery within three weeks. The scoring system was: 2 points for biparietal diameter, head circumference, AC, or femur length >or=90% for GA, or if the amniotic fluid index (AFI) was >or=24 cm; for biometric parameters <90% or with AFI <24 cm, 0 points. The predictive values for detection of shoulder dystocia were calculated. RESULTS: Of the 225 cohorts that met the inclusion criteria the rate of macrosomia was 39% and among vaginal deliveries (n = 120) shoulder dystocia occurred in 12% (15/120; 95% confidence interval (CI) 7-20%). The sensitivity of EFW >or=4500 g to identify a newborn with shoulder dystocia was 0% (95% CI 0-21%), positive predictive values 0% (95% CI 0-46%), and likelihood ratio of 0. For a macrosomia score >6, the corresponding values were 20% (4-48%), 25% (5-57%) and 2.3. CONCLUSION: Though the scoring system can identify macrosomia, it offers no advantage over EFW. The scoring system and EFW are poor predictors of shoulder dystocia.     

Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects.

Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax and KD) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher Bmax in all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. Bmax was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT2A Bmax in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.     

Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer.     

Effectiveness of training on the community skills of children with intellectual disabilities

Background: Children with intellectual disabilities often have difficulties in daily tasks, requiring training to increase functional independence. This study measured the effectiveness of community skills training in a telephone task and a shopping task, and examined if community-based training was more effective than classroom-based training. Material and methods: A randomized control trial with 40 children aged 9–11years was completed. Intervention groups attended an eight-week training programme; the control group received no treatment. One intervention group practised skills in local shops. All participants were assessed before and after treatment in a shopping task and telephone task, using task analysis methodology. Results: Data showed a highly statistically significant difference between intervention and control groups in the shopping task (p=0.007); however, there was no significant difference between classroom and classroom supplemented by community-based learning in the shopping task. There was no significant difference between the intervention and control groups in the telephone task. Conclusion: Results suggested that skills training was effective in one of the skill areas with this client group. Further research is required to determine if community-based training is more effective than classroom-based learning.     

Bone morphogenetic protein signaling:a promising target for white matter protection in perinatal brain injury

正Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction(IUGR).Injury of all types can impact the motor and cognitive abilities of survivors.The mechanisms leading to disability are not completely understood.Here we discuss the role of the bone morphogenetic protein(BMP)signaling     

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.