No abstract

Apart from their key role in immunologic signaling, cytokines are thought to play a part in ovulation, implantation, placentation, and parturition. There is mounting evidence that cytokines can contribute to preterm births associated with intrauterine infection. This study measured levels of cytokines produced by maternal peripheral blood mononuclear cells after stimulation by mitogen, autologous placental cells, and an extract of trophoblast antigen. Cytokine levels were compared in 30 women admitted in active preterm labor with intact membranes who had preterm delivery (PTD) and 54 control women who had had at least 3 normal pregnancies. Mean gestational ages were 26.8 weeks in the PTD group and 39.4 weeks in the control women. Without stimulation, serum levels of interleukin-6 (IL-6) were significantly higher in the PTD group from the second trimester onward. Levels of interferon-␥ (IFN-␥) also were higher in PTD, whereas levels of tumor necrosis factor-␣ were significantly higher in normal women. Analysis of stimulated cultures confirmed significantly higher levels of the type 1 cytokines IFN-␥ and IL-2 in the PTD group. Women with normal pregnancies exhibited significantly greater production of the type 2 cytokines IL-4, IL-5, and IL-10. The ratios of type 2 to type 1 cytokines suggested a bias to type 1 cytokines in women with PTD. This study indicated a bias toward increased production, by maternal lymphocytes of women with PTD, of type 1 cytokines that are known to induce numerous cytotoxic and inflammatory actions. Production of type 2 cytokines, which augment humoral immunity, is less evident in these women. Reportedly normal pregnancy is associated with a predisposition to type 2 immunity, whereas predominantly type 1 reactivity can lead to failed pregnancy. ABSTRACTApproximately 1% of pregnant women are asthmatic and the prevalence could be increasing, like it is in the general population. The authors used data from a nested case-control study to learn whether maternal asthma is associated with a greater risk of preterm labor and delivery. The study group included 312 women who delivered before 37 completed weeks gestation and, as a control group, 424 women who delivered a singleton infant at term. Women with a history of asthma were approximately twice as likely as others to have preterm delivery (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.01-4.09). A slightly stronger association (OR, 2.37; 95% CI, 1.15-4.88) was evident after adjusting for maternal age, race/ethnicity, parity, Medicaid payment status, and smoking during pregnancy. Asthma correlated with a greater than 2-fold increase in risk of both spontaneous and medically induced preterm delivery, but the association was statistically significant only for the latter. Maternal asthma was associated with both moderate (34-36 weeks) and very (before 34 weeks) preterm deliveries. These findings point to an increased risk of preterm delivery in asthmatic women. ABSTRACTPreterm delivery before 37 completed weeks gestation remains the major...

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer's female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei. Increased activation was also present in the lateral putamen and adjoining parts of the claustrum. Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation was observed. Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.

Injections of HRP in the nucleus raphe magnus and adjoining medial reticular formation in the cat resulted in many labeled neurons in the lateral part of the bed nucleus of the stria terminalis (BNST) but not in the medial part of this nucleus. HRP injections in the nucleus raphe pallidus and in the C2-segment of the spinal cord did not result in labeled neurons in the BNST. Injections of 3H-leucine in the BNST resulted in many labeled fibers in the brain stem. Labeled fiber bundles descended by way of the medial forebrain bundle and the central tegmental field to the lateral tegmental field of pons and medulla. Dense BNST projections could be observed to the substantia nigra pars compacta, the ventral tegmental area, the nucleus of the posterior commissure, the PAG (except its dorsolateral part), the cuneiform nucleus, the nucleus raphe dorsalis, the locus coeruleus, the nucleus subcoeruleus, the medial and lateral parabrachial nuclei, the lateral tegmental field of caudal pons and medulla and the nucleus raphe magnus and adjoining medial reticular formation. Furthermore many labeled fibers were present in the solitary nucleus, and in especially the peripheral parts of the dorsal vagal nucleus. Finally some fibers could be traced in the marginal layer of the rostral part of the caudal spinal trigeminal nucleus. These projections appear to be virtually identical to the ones derived from the medial part of the central nucleus of the amygdala (Hopkins and Holstege 1978). The possibility that the BNST and the medial and central amygdaloid nuclei must be considered as one anatomical entity is discussed.

ObjectiveTo assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.Study designThis retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum. Primary adverse outcome was defined as death, cerebral palsy, Bayley Scales of Infant and Toddler Development, third edition, motor or cognitive composite scores at 2 years of <85, or IQ at school age of <85.ResultsIn cohort 1 (n = 97) and cohort 2 (n = 76) the grey matter subscore was an independent predictor of adverse outcome at 2 years (cohort 1, OR, 1.6; 95% CI, 1.3-1.9; cohort 2, OR, 1.4; 95% CI, 1.2-1.6), and school age (cohort 1, OR, 1.3; 95% CI, 1.2-1.5; cohort 2, OR, 1.3; 95% CI, 1.1-1.6). The white matter and cerebellum subscore did not add to the predictive value. The positive predictive value, negative predictive value, and area under the curve for the grey matter subscore were all >0.83 in both cohorts, whereas the specificity was >0.91 with variable sensitivity.ConclusionA novel MRI score, which includes diffusion-weighted imaging and assesses all brain areas of importance in infants with therapeutic hypothermia after perinatal asphyxia, has predictive value for outcome at 2 years of age and at school age, for which the grey matter subscore can be used independently.

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X-SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.

Mutations in CHD7 are the major cause of CHARGE syndrome, an autosomal dominant disorder with an estimated prevalence of 1/15,000. We have little understanding of the disruptions in the developmental programme that underpin brain defects associated with this syndrome. Using mouse models, we show that Chd7 haploinsufficiency results in reduced Fgf8 expression in the isthmus organiser (IsO), an embryonic signalling centre that directs early cerebellar development. Consistent with this observation, Chd7 and Fgf8 loss-of-function alleles interact during cerebellar development. CHD7 associates with Otx2 and Gbx2 regulatory elements and altered expression of these homeobox genes implicates CHD7 in the maintenance of cerebellar identity during embryogenesis. Finally, we report cerebellar vermis hypoplasia in 35% of CHARGE syndrome patients with a proven CHD7 mutation. These observations provide key insights into the molecular aetiology of cerebellar defects in CHARGE syndrome and link reduced FGF signalling to cerebellar vermis hypoplasia in a human syndrome.DOI: http://dx.doi.org/10.7554/eLife.01305.001

ACWMp and GWDL can improve the visual diagnosis of hippocampal sclerosis, particularly in patients with no or restricted hippocampal abnormalities. These results suggest that loss of myelin may be the underlying cause of GWDL in association with hippocampal sclerosis.