Miracle-dz/UniFAR-FTUs huggingface dataset:
Perinatal and maternal risk factors for autism spectrum disorders in New South Wales, Australia.

BACKGROUND This study was commenced in 1999 with the aim of examining risk factors for autism using established population-based data for comparison. METHODS Cases were ascertained using active surveillance and compared with birth data. RESULTS Four risk factors were found to be significantly associated with autism using binary logistic regression analysis; being male [adjusted odds ratio (OR) 4.7, 95% confidence interval (CI) 3.2-7.0], being born prematurely (adjusted OR 2.2, 95% CI 1.5-3.5), having maternal age >/=35 years (adjusted OR 1.7, 95% CI 1.2-2.4) and having a mother born outside Australia (adjusted OR 1.4, 95% CI 1.0-1.9). For analysis completed for pregnancies, rather than live births, multiple birth was also a significant risk factor for one or more children of the pregnancy to be affected by autism (adjusted OR 2.5, 95% CI 1.1-5.5). There was a statistically significant trend towards increasing risk with increasing risk factor 'dose' for gestational age (P = 0.019), multiple birth (P = 0.016) and maternal age (P < 0.001). For mother's country of birth the group with the highest risk were children of mother's born in south-east or north-east Asia. There was a non-significant trend towards a higher proportion of children with developmental disability having risk factors. CONCLUSION Replication of risk factors from previous studies and a significant risk factor 'dose' effect add to growing evidence that maternal and perinatal factors are low magnitude risk factors for autism. The association between developmental disability and autism risk factors warrants further examination.
Estudo randomizado, cruzado e duplo cego para a avaliação da eletroestimulação intravaginal no tratamento da dor pelvica cronica

Este estudo avaliou a eficacia da eletroestimulacao intravaginal com corrente ativa (EIVA) comparada a um grupo de controle com eletroestimulacao intravaginal sem corrente ativa (placebo) (EIVP) em mulheres com dor pelvica cronica (DPC). Foi realizado um ensaio clinico controlado, duplo-cego, randomizado cruzado. Foram avaliadas 26 mulheres com DPC sem causa aparente, que foram submetidas a 10 sessoes de eletroterapia intravaginal com corrente ativa e 10 sessoes de eletroterapia intravaginal sem corrente ativa (placebo). O estudo foi realizado na Secao de Fisioterapia do Centro de Atencao Integral a Saude da Mulher da Universidade Estadual de Campinas. Foi utilizado o programa para dor cronica difusa com frequencia de 8Hz, com variacao de intensidade e frequencia, largura de pulso de1mS e intensidade suportavel para cada paciente (em mA). O tratamento foi realizado duas a tres vezes por semana em aplicacoes de 30 minutos e a dor foi avaliada atraves da escala analoga visual, antes e apos cada sessao, e imediatamente apos o tratamento completo. Quinze mulheres foram alocadas inicialmente para o grupo EIVA e 11 para o grupo EIVP. Comparando-se a intensidade da dor ao longo do tempo, observou-se que ambos os grupos reduziram a queixa de dor pelvica, porem a EIVA foi mais eficiente em aliviar os sintomas dolorosos (p = 0,0005) em comparacao a EIVP (p= 0,0253). A eficacia da EIVA foi confirmada quando se cruzaram os dados para os grupos de tratamento. A diminuicao da dor foi estatisticamente significativa em todas as ocasioes, quando se mudou do grupo placebo para o ativo (p=0,0361). As queixas de dispareunia superficial e profunda nao apresentaram alteracao ao longo dos tratamentos, independentemente do grupo no qual a mulher iniciou o estudo. Em conclusao, EIVA foi mais eficaz do que EIVP no alivio dos sintomas dolorosos de mulheres com DPC Abstract
Energy‐Level Modulation of Small‐Molecule Electron Acceptors to Achieve over 12% Efficiency in Polymer Solar Cells

Fine energy-level modulations of small-molecule acceptors (SMAs) are realized via subtle chemical modifications on strong electron-withdrawing end-groups. The two new SMAs (IT-M and IT-DM) end-capped by methyl-modified dicycanovinylindan-1-one exhibit upshifted lowest unoccupied molecular orbital (LUMO) levels, and hence higher open-circuit voltages can be observed in the corresponding devices. Finally, a top power conversion efficiency of 12.05% is achieved.
Cadherin flexibility provides a key difference between desmosomes and adherens junctions

Significance We present here an entirely novel concept in the field of cell–cell adhesion, whereby the flexibility of the extracellular domains of cadherin molecules determines the characteristics and behavior of intercellular junctions. The structure of the ectodomain of the desmosomal cadherin desmoglein 2 shows it is flexible in its calcium-bound form. This flexibility of the desmosomal cadherin ectodomains may be key in facilitating a unique property of desmosomes: the ability to switch from strong calcium-independent hyperadhesion in adult tissues to weaker calcium-dependent adhesion in wounds. Desmosomes and adherens junctions are intercellular adhesive structures essential for the development and integrity of vertebrate tissue, including the epidermis and heart. Their cell adhesion molecules are cadherins: type 1 cadherins in adherens junctions and desmosomal cadherins in desmosomes. A fundamental difference is that desmosomes have a highly ordered structure in their extracellular region and exhibit calcium-independent hyperadhesion, whereas adherens junctions appear to lack such ordered arrays, and their adhesion is always calcium-dependent. We present here the structure of the entire ectodomain of desmosomal cadherin desmoglein 2 (Dsg2), using a combination of small-angle X-ray scattering, electron microscopy, and solution-based biophysical techniques. This structure reveals that the ectodomain of Dsg2 is flexible even in the calcium-bound state and, on average, is shorter than the type 1 cadherin crystal structures. The Dsg2 structure has an excellent fit with the electron tomography reconstructions of human desmosomes. This fit suggests an arrangement in which desmosomal cadherins form trans interactions but are too far apart to interact in cis, in agreement with previously reported observations. Cadherin flexibility may be key to explaining the plasticity of desmosomes that maintain tissue integrity in their hyperadhesive form, but can adopt a weaker, calcium-dependent adhesion during wound healing and early development.
Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells

Significance The present study provides evidence for a role of glutamate as a neuromodulator of the afferent nociceptive information. Our results show that the nociceptive impulse generated by an inflammatory event in the peripheral tissue is regulated in the dorsal root ganglia (DRG) by a system that involves satellite glial cells and glutamatergic NMDA receptors. To our knowledge, this work is one of the first demonstrations of the involvement of glutamate in a modulatory process in the DRG, a site where there are no synapses, in addition to its classical role as a neurotransmitter. The present study evaluated the role of N-methyl-d-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist d(-)-2-amino-5-phosphonopentanoic acid (d-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in thepaw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.
A novel connection: Obstructive sleep apnoea and diabetic neuropathy

Rationale: An ever-growing number of studies have shown that obstructive sleep apnoea(OSA) is associated with insulin resistance, glucose intolerance and type 2 diabetes, independent of obesity. OSA is associated with many of the pathophysiological deficits that are found in diabetes, it seems reasonable to speculate that OSA could play an important role in the development or progression of Diabetic peripheral neuropathy (DPN). Objectives: To evaluate the relation between OSA and peripheral neuropathy in patients with type 2 diabetes. Design: A cross-sectional study conducted between May 2011 and August 2012 in four hospitals in Turkey. Patients And Methods: Three hundred forty six patients with type 2 diabetes mellitus were recruited. OSA was evaluated with overnight-attended polysomnography. DPN was diagnosed with electromyography, nerve conduction velocity tests, the Rochester Neuropathy Score method, the Michigan Neuropathy Screening Instrument. Results: In the study population, 197( 57%) patients had OSA. The proportion of subjects with diabetic peripheral neuropathy in the different categories was 29.8% among subjects without OSA, 44.3% among those with mild to moderate disease, and 72.0% among those with severe OSA (p<0.001). In the multivariate logistic regression model, after adjustment for all significant univariate covariates, OSA was identified as independently associated with diabetic neuropathy (odds ratio: 3.07; 95% confidence interval, 1.32–5.64; P = 0.0027). Conclusion: There is an independent association between OSA and diabetic peripheral neuropathy and the degree of AHI and the severity of nocturnal hypoxemia corralate with the severity of DPN.
Stress in mothers of preterm infants in Bangladesh: associations with family, child and maternal factors and children's neuro-development.

BACKGROUND The aim of this paper was to ascertain stress experienced by mothers of prospectively followed up preterm infants, and associations with family, child and maternal factors and children's neuro-development. METHODS Within a follow-up study of preterm infants<33 weeks gestational age at a Child Development Center in Dhaka Shishu Hospital, mothers were interviewed with the Self-Report Questionnaire (SRQ) at each visit. Association between SRQ scores and child, family and maternal variables at first and final visit and children's neuro-developmental outcomes was determined. RESULTS Low income mothers were more compliant (54%) compared with the defaulters (31%) (P=0.0001) among the 159 mothers enrolled. Of the 88 mothers who were followed up until a mean age of 22 months of their child, 29.3% were at high risk for psychiatric morbidity at first visit compared with 23.9% on their last visit. Use of abortifacients (P=0.026) and higher maternal age (P=0.040) were significantly associated with maternal stress at first visit; while at last follow-up, total number of visits had the most significant association (P=0.041). Twenty-five per cent and 19% of mothers were at risk for psychiatric morbidity in children developing normally and those with neuro-developmental impairments respectively. CONCLUSIONS Mothers at risk for psychiatric morbidity can be helped through follow-up support within public hospitals close to their homes, which is most availed by low income families. Neuro-developmental monitoring of high-risk infants closer to homes may be more feasible in resource poor countries than reliance on hospital visits, which increase stress. Biological markers of stress and coping strategies need further research.
GlioVis data portal for visualization and analysis of brain tumor expression datasets.

© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. doi:10.1093/neuonc/now199 Advance Access date 14 September 2016 the effects they observed could be influenced by inhibition of other types of Trk receptors or signaling molecules downstream of Trk. We have recently started a series of experiments aiming to verify whether specific TrkB inhibition reduces glioma cell proliferation using ANA-12, a small-molecule selective TrkB antagonist. Our first results showed that ANA-12 effectively and dose-dependently reduces the viability of a human glioblastoma cell line with almost complete disappearance of cultured cells 72 hours after treatment (Fig. 1). Therefore, selective TrkB inhibition might prove to be an effective experimental therapeutic strategy, possibly with fewer off-target toxicities compared with multitarget drugs in patients with astrocytomas harboring oncogenic TrkB.
Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma

Background Interferons (IFNs) are cytokines typically induced upon viral infection but are constitutively expressed also in the absence of acute infection. The physiological role of autocrine and paracrine IFN signaling, however, remains poorly understood, and its function in glioblastoma has not been explored in depth. Methods Using RNA interference-mediated gene silencing, we characterized constitutive type I IFN signaling and its role in human glioma cells. Results We observed constitutive expression of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) and myxovirus resistance protein A (MxA), a classical IFN-response marker, in the absence of exogenous IFN-β. In vivo, we found higher MxA expression in gliomas than in normal tissue, suggesting that IFN signaling is constitutively active in these tumors. To demonstrate the presence of an autocrine type I IFN signaling loop in glioma cells in vitro, we first confirmed the expression of the type I alpha/beta receptor (IFNAR)1/2, and its ligands, IFN-α and IFN-β. Small interfering RNA-mediated receptor gene silencing resulted in reduced expression of MxA at mRNA and protein levels, as did gene silencing of the ligands, corroborating the hypothesis of an autocrine signaling loop in which type I IFNs induce intracellular signaling through IFNAR1/2. On a functional level, following IFNAR1 or IFNAR2 gene silencing, we observed reduced programmed death ligand 1 (PD-L1) and major histocompatibility complex (MHC) class I and II expression as well as an enhanced susceptibility to natural killer immune cell lysis, suggesting that autocrine IFN signaling contributes to the immune evasion of glioma cells. Conclusions Our findings point to an important role of constitutive IFN signaling in glioma cells by modulating their interaction with the microenvironment.
Prävention der erektilen Dysfunktion

The prevention of erectile dysfunction is primarily based on the maintenance of adequate function of the arterial system or prevention of atherosclerosis. There is less eviAus der 1Radiologischen Praxis Prof. Böck, München, sowie der Medical Faculty, University of Latvia, Riga, und dem 2Zentrum für Operative Medizin, Klinik und Poliklinik für Urologie, Universitätsklinikum Hamburg-Eppendorf Korrespondenzadresse: Prof. Dr. med. Johannes C. Böck, D-81479 München, Wolfratshauser Straße 107a; E-Mail: prof.dr.boeck@arcor.de dence but the data suggest that the improvement of the oxygenation of the corpora cavernosa by regular erections is the second most important preventive measure. The frequency, duration and quality of erections can be improved pharmacologically (phosphodiesterase-5 inhibitors on demand or before bedtime) or by other measures. Both sexual intercourse and masturbation seem to be protective. The pharmacological approach has the charming aspect that the preventive effects occur without individual action during sleep. Whether, for which specific risk groups or from what age on such measures can be recommended is yet unclear. Blickpunkt DER MANN 2009; 7 (1): 10–4.
Autistic spectrum disorder traits in children with attention deficit hyperactivity disorder.

BACKGROUND Current classification systems do not allow for comorbid diagnoses of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Children with ADHD are often screened for ASD during clinical assessment and when recruited to clinical trials. We predicted that children with ADHD would have more autistic traits than controls and that certain traits would be more prevalent. METHODS The clinically referred sample consisted of 30 children with ADHD and 30 matched controls aged 9-15 years. Children were screened for ASD traits using the Social Aptitudes Scale (SAS) and the Social Communication Questionnaire (SCQ). RESULTS We found that ASD traits were significantly higher in children with ADHD than controls. None of the children received a diagnosis of autism or ASD. However, a large proportion (28% using the SCQ and 62% using the SAS) of children with ADHD reached screening thresholds for a predictive diagnosis of ASD. Relative to controls, children with ADHD had significantly higher levels of communication and social deficits, but not repetitive behaviours. CONCLUSION Further work is needed to establish whether autistic-like communication and social difficulties in children with ADHD are part of the broader ASD phenotype or are specific to ADHD.
COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset

Significance Cancer-related inflammation promotes progression and therapy resistance in tumors of adulthood. Knowledge concerning the significance of inflammation in childhood malignancies has been limited. Neuroblastoma is an embryonal tumor of early childhood with poor prognosis despite intensified therapy, and biological understanding is necessary to develop novel therapies. We found high-risk neuroblastoma, in particular the therapy-resistant subset with chromosome 11q-deletion, to be inflammatory driven and characterized by high expression of the COX/microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E2 (PGE2) pathway that correlates with metastatic stage and poor clinical outcome. We further detected infiltrating cancer-associated fibroblasts expressing mPGES-1, the essential enzyme for synthesis of PGE2, promoting tumor growth, angiogenesis, and metastatic spread. Treatment targeting this inflammatory pathway provides a therapeutic option for neuroblastoma and other cancers. The majority of solid tumors are presented with an inflammatory microenvironment. Proinflammatory lipid mediators including prostaglandin E2 (PGE2) contribute to the establishment of inflammation and have been linked to tumor growth and aggressiveness. Here we show that high-risk neuroblastoma with deletion of chromosome 11q represents an inflammatory subset of neuroblastomas. Analysis of enzymes involved in the production of proinflammatory lipid mediators showed that 11q-deleted neuroblastoma tumors express high levels of microsomal prostaglandin E synthase-1 (mPGES-1) and elevated levels of PGE2. High mPGES-1 expression also corresponded to poor survival of neuroblastoma patients. Investigation of the tumor microenvironment showed high infiltration of tumor-promoting macrophages with high expression of the M2-polarization markers CD163 and CD206. mPGES-1–expressing cells in tumors from different subtypes of neuroblastoma showed differential expression of one or several cancer-associated fibroblast markers such as vimentin, fibroblast activation protein α, α smooth muscle actin, and PDGF receptor β. Importantly, inhibition of PGE2 production with diclofenac, a nonselective COX inhibitor, resulted in reduced tumor growth in an in vivo model of 11q-deleted neuroblastoma. Collectively, these results suggest that PGE2 is involved in the tumor microenvironment of specific neuroblastoma subgroups and indicate that therapeutic strategies using existing anti-inflammatory drugs in combination with current treatment should be considered for certain neuroblastomas.
Cross-talk and regulatory interactions between the essential response regulator RpaB and cyanobacterial circadian clock output

Significance In cyanobacteria, genome-wide transcriptional oscillations and cell division are under the control of the global response regulator RpaA. Here we show that regulator of phycobilisome-associated B (RpaB), a closely related response regulator that is essential in the model cyanobacterium Synechococcus elongatus PCC 7942, is involved in complex regulatory interactions with the RpaA signaling system. RpaB influences circadian timing and cell dimensions by modulating the RpaA∼P levels and by controlling a subset of the RpaA target genes. Our results suggest that regulatory interactions between RpaA and RpaB are required for transmission of updated time information to the level of gene expression, paving the way to uncover regulatory mechanisms involved in integration of temporal and environmental information. The response regulator RpaB (regulator of phycobilisome associated B), part of an essential two-component system conserved in cyanobacteria that responds to multiple environmental signals, has recently been implicated in the control of cell dimensions and of circadian rhythms of gene expression in the model cyanobacterium Synechococcus elongatus PCC 7942. However, little is known of the molecular mechanisms that underlie RpaB functions. In this study we show that the regulation of phenotypes by RpaB is intimately connected with the activity of RpaA (regulator of phycobilisome associated A), the master regulator of circadian transcription patterns. RpaB affects RpaA activity both through control of gene expression, a function requiring an intact effector domain, and via altering RpaA phosphorylation, a function mediated through the N-terminal receiver domain of RpaB. Thus, both phosphorylation cross-talk and coregulation of target genes play a role in the genetic interactions between the RpaA and RpaB pathways. In addition, RpaB∼P levels appear critical for survival under light:dark cycles, conditions in which RpaB phosphorylation is environmentally driven independent of the circadian clock. We propose that the complex regulatory interactions between the essential and environmentally sensitive NblS-RpaB system and the SasA-RpaA clock output system integrate relevant extra- and intracellular signals to the circadian clock.