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Several studies have investigated reproductive outcomes following surgical treatment of colorectal endometriosis, mainly segmental colorectal resection. This study examines pregnancy and live birth rates of women with rectosigmoid endometriosis not treated by surgery.A retrospective analysis of data collected between May 2009 and January 2020 related to 215 women affected by rectosigmoid endometriosis wishing to conceive. Patients had a diagnosis of rectosigmoid endometriosis by transvaginal ultrasonography and magnetic resonance imaging enema. Patients with estimated bowel stenosis70% at computed tomographic colonography and/or subocclusive/occlusive symptoms were excluded.During the median length of follow-up of 31 months (range 13-63 months), the total pregnancy and live birth rates of the study population were 47.9% and 45.1%, respectively. Sixty-two women had a live birth after natural conception (28.8%; 95% confidence interval [CI] 22.8-35.6%) with a median time required to conceive of 10 months (range 2-34 months). Eighty-three women underwent infertility treatments (38.6%, 95% CI 32.1-45.5%); among these, 68 patients underwent IVF either directly (n = 51) or after intrauterine insemination (IUI) failure (n = 17). Time to conception was significantly higher in women having conceived by IVF than in those having conceived naturally (P 0.001) or by IUI (P = 0.006). In patients undergoing IVF cycles, a worsening of some pain and intestinal symptoms was observed.At median follow-up of 31 months, women with rectosigmoid endometriosis have a 48% pregnancy rate. However, these patients must be referred to centres specialized in managing endometriosis to properly assess symptoms and degree of bowel stenosis.

Disorders with neurodevelopmental aetiology such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and Schizophrenia share commonalities at many levels of investigation despite phenotypic differences. Evidence of genetic overlap has led to the concept of a continuum of neurodevelopmental impairment along which these disorders can be positioned in aetiological, pathophysiological and developmental features. This concept requires their simultaneous comparison at different levels, which has not been accomplished so far. Given that cognitive impairments are core to the pathophysiology of these disorders, we provide for the first time differentiated head-to-head comparisons in a complex cognitive function, visual search, decomposing the task with eye movement-based process analyses. N = 103 late-adolescents with schizophrenia, ADHD, ASD and healthy controls took a serial visual search task, while their eye movements were recorded. Patients with schizophrenia presented the greatest level of impairment across different phases of search, followed by patients with ADHD, who shared with patients with schizophrenia elevated intra-subject variability in the pre-search stage. ASD was the least impaired group, but similar to schizophrenia in post-search processes and to schizophrenia and ADHD in pre-search processes and fixation duration while scanning the items. Importantly, the profiles of deviancy from controls were highly correlated between all three clinical groups, in line with the continuum idea. Findings suggest the existence of one common neurodevelopmental continuum of performance for the three disorders, while quantitative differences appear in the level of impairment. Given the relevance of cognitive impairments in these three disorders, we argue in favour of overlapping pathophysiological mechanisms.

Background Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. Methods From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. Results A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26–95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1–30) and 4.94 mg/L (range 0.1–28.3), respectively. Median VoD was 249.5 cm3 (range 9.9–1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. Conclusions Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.

Intestinal endometriosis occurs in 4% to 37% of women with deep endometriosis (DE). Noninvasive diagnosis of presence and characteristics of rectosigmoid endometriosis permits the best counseling of patients and ensures best therapeutic planning. Magnetic resonance enema (MR-e) is accurate in diagnosing DE. After colon cleansing, rectal distention and opacification improves the performance of MR-e in diagnosing rectosigmoid endometriosis. MR imaging cannot optimally assess the depth of penetration of endometriosis in the intestinal wall. There is a need for multicentric studies with a larger sample size to evaluate reproducibility of MR-e in diagnosis of rectosigmoid endometriosis for less experienced radiologists.

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10–13 years with ADHD, ASD with (ASD+) or without (ASD−) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD− group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

This paper will offer several vantage points for interpreting a new social phenomenon: the flaunting of pregnancy in the public space, and in the media space in particular. In the last twenty years, the cultural meaning of pregnancy has been entirely upended: once a period of waiting, of suspension, almost mysterious and concealed, wrapped in prohibitions and fears, and surrounded by silence, pregnancy now seems to be something to be chronicled, savored and even exhibited by displaying the belly – painted or decorated – as if it were a trophy. Through thirty in-depth interviews with women in a range of occupations – midwives, photographers, belly painters and journalists – throughout Italy, we will attempt to explore the cultural meanings of this change. L’obiettivo di questo contributo è fornire alcune chiavi interpretative per leggere un fenomeno sociale nuovo: l’esibizione della gravidanza nello spazio pubblico, in particolare quello mediatico. Negli ultimi venti anni si è infatti verificato un vero e proprio ribaltamento del significato culturale della gravidanza: da tempo dall’attesa, di sospensione, quasi misterioso e nascosto, avvolto in divieti e paure, circondato dal silenzio, oggi la gravidanza appare un momento da raccontare, fruire, anche esibire, attraverso l’esposizione della pancia – dipinta o decorata – come un trofeo. A partire da trenta interviste in profondità realizzate a ostetriche, fotografe, pittrici di pance (belly painters), giornaliste in tutta Italia, cercheremo di indagare i significati culturali di questo cambiamento.

OBJECTIVES Rectosigmoid involvement by endometriosis causes intestinal symptoms such as constipation, diarrhea, and dyschezia. A precise diagnosis about the presence, location, and extent of bowel implants is required to plan the most appropriate treatment. The aim of the study was to compare the accuracy of magnetic resonance with distension of the rectosigmoid (MR-e) with computed colonography (CTC) for diagnosing rectosigmoid endometriosis. METHODS This study was based on the retrospective analysis of a prospectively collected database of patients with suspicion of rectosigmoid endometriosis who underwent both MR-e and CTC, and subsequently were treated by laparoscopy. The findings of imaging techniques were compared with surgical and histological results. RESULTS Of 90 women included in the study, 44 (48.9%) had rectosigmoid nodules and underwent bowel surgery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the diagnosis of rectosigmoid endometriosis were 88.6%, 93.5%, 92.9%, 89.6%, and 91.1% for CTC, and 93.2%, 97.9%, 97.6%, 93.8%, and 95.6% for MR-e. There was no significant difference in the accuracy of both radiologic examinations for diagnosing rectosigmoid endometriosis (P = 0.344). However, MR-e was more accurate than CTC in estimating the largest diameter of the main rectosigmoid nodule (P < 0.001). The pain perceived by the patients was significantly lower during MR-e than during CTC (P < 0.001). CONCLUSIONS MR-e and CTC have similar diagnostic performance for the diagnosis of rectosigmoid involvement of endometriosis. However, MR-e is more accurate in the estimation of the largest diameter of main rectosigmoid nodule and more tolerated than CTC.

Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis. DCBE provides a complete overview of the entire colon and allows detecting cecal nodules. The accuracy of DCBE is operator dependent and, thus, it may have low specificity. It does not allow identifying the cause of the mass effect. DCBE requires the administration of barium and exposure to radiation. REU precisely estimates the distance between the rectosigmoid nodule and the anal verge. However, it allows investigating only the distal part of rectosigmoid, it misses anterior pelvic lesions, and it has poor sensitivity for the diagnosis of endometriomas. MDCT-e is accurate and reproducible in diagnosing intestinal endometriosis and in assessing its characteristics: the largest diameter of the nodule, the distance between the distal part of the nodule and the anal verge, and depth of infiltration of endometriosis in the intestinal wall. MDCT-e requires the administration of iodinated contrast medium (CM) and the exposure to radiations. CTC has good performance in the diagnosis of rectosigmoid endometriosis. It allows estimating the degree of intestinal stenosis CTC, and the distance between the intestinal endometriotic nodule and the anal verge. It requires exposure to radiations, and it may require the administration of an iodinated CM.

Objective: Relationships between sleep, screen-based media, and ADHD symptomatology were investigated using a case- and community-based approach. Method: N = 357 healthy and N = 61 children with ADHD (12.72 ± 2.83 years) completed a sleep and media questionnaire. To measure ADHD symptomatology, parents filled out the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale. Two samples were formed: a matched ( N = 61 patients and N = 61 controls) and a community sample ( N = 357 healthy participants and N = 20 patients). Results: Compared with controls, participants with ADHD reported delayed sleep onset and more screen time on school days. Adolescent patients showed more behavior promoting delayed sleep phase. In the community sample, media time, sleep deviation, and circadian rhythm were correlated with ADHD symptomatology. Furthermore, media time, sleep-wake behavior, and sleep deviation were predictive of ADHD symptomatology (variance explained = 4%-15%). Conclusion: Longer media time and inadequate sleep-wake behavior increase the risk of ADHD-like symptoms. However, research using objective assessments is needed to disentangle this distinct association and to provide possible directions for intervention.

Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders. Method: We examined performance of ASD patients with (ASD+) and without (ASD–) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing. Results: We found that patients with ADHD or ASD+, but not ASD–, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders. Conclusion: Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism.

Several recent studies have demonstrated reduced visual aftereffects, particularly to social stimuli, in autism spectrum disorder (ASD). This putative impairment of the adaptive mechanism in ASD has been put forward as a possible explanation for some of the core social problems experienced by children with ASD (e.g., facial emotion or identity recognition). We addressed this claim in children with ASD and typically developing children by using an established methodology and morphed auditory stimulus set for eliciting robust aftereffects to vocal expressions and phonemes. Although children with ASD were significantly worse at categorizing the vocal expressions compared with the control stimuli (phoneme categorization), aftereffect sizes in both tasks were identical in the two participant groups. Our finding suggests that the adaptation mechanism is not universally impaired in ASD and is therefore not an explanation for the social perception difficulties in ASD.

The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ ≤ 70; LIQ) and higher intellectual abilities (IQ > 70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N = 583 families) and the Autism Genome Project cohort (AGP-ALL: N = 2001 families), split into HIQ, and LIQ subgroups. We did not identify any association withstanding correction for multiple testing. However, we report a replicated nominal significant under-transmission (OR

Objective To compare the accuracy of magnetic resonance enema (MR-e) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis. Methods This prospective study included 286 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent MR-e and RWC-TVS before laparoscopic excision of endometriotic lesions. The findings of MR-e and RWC-TVS were compared with surgical and histological results. Results Of the 286 patients included in the study, 151 (52.8%) had rectosigmoid endometriosis. MR-e and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.063). In the diagnosis of rectosigmoid endometriosis with MR-e, the sensitivity was 95.4% (95% CI, 90.7-99.1%), specificity was 97.8% (95% CI, 93.6-99.5%), positive predictive value (PPV) was 98.0% (95% CI, 94.1-99.6%), negative predictive value (NPV) was 95.0% (95% CI, 89.9-97.9%), positive likelihood ratio (LR+) was 42.91 (95% CI, 14.01-131.46) and negative likelihood ratio (LR-) was 0.05 (95% CI, 0.02-0.10). For diagnosis with RWC-TVS, sensitivity was 92.7% (95% CI, 87.3-96.3%), specificity was 97.0% (95% CI, 92.6-99.2%), PPV was 97.2% (95% CI, 93.0-99.2%), NPV was 92.3% (95% CI, 86.6-96.1%), LR+ was 31.29 (95% CI, 11.90-82.25) and LR- was 0.08 (95% CI, 0.04-0.13). MR-e and RWC-TVS underestimated the size of the endometriotic nodules; for both imaging techniques the underestimation was greater for nodules with a diameter ≥ 30 mm. There was no significant difference in the mean intensity of pain experienced by the patients during the two examinations. Conclusions RWC-TVS should be the first-line investigation in patients with clinical suspicion of rectosigmoid endometriosis and physicians should be trained in performing this examination. Considering that MR-e is more expensive than RWC-TVS, it should be used only when the findings of RWC-TVS are unclear. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Objectives To compare the performance of computed tomographic colonography (CTC) and rectal water-contrast transvaginal sonography (RWC-TVS) in the diagnosis of rectosigmoid endometriosis, and compare precision in estimating the length of the rectosigmoid nodules and the distance between the nodules and the anal verge. Methods This prospective study included 70 patients of reproductive age with clinical suspicion of rectosigmoid endometriosis. Patients underwent RWC-TVS and CTC before laparoscopic excision of endometriotic nodules. The findings of RWC-TVS and CTC were compared with surgical and histological results. Results Of the 70 patients included in the study, 40 (57.1%) had rectosigmoid endometriosis. CTC and RWC-TVS had similar accuracy in the diagnosis of rectosigmoid endometriosis (P = 0.508) and similar precision in estimating the length of the endometriotic nodules (P = 0.077). CTC was more precise than RWC-TVS in estimating the distance between the rectosigmoid nodule and the anal verge (P

Over 10 years ago, multidetector computerized tomography enema (MDCT-e) was proposed for the diagnosis of bowel endometriosis. This technique is based on the retrograde distention of the colon, cecum, and last ileal loops with saline solution. The exam requires bowel cleansing, intestinal hypotonization, and the administration of iodinated contrast medium. Several studies demonstrated that MDCT-e has good performance not only in diagnosing the presence of intestinal endometriotic nodules but also in assessing the characteristics of the lesions (such as their largest diameter and distance from the anal verge). MDCT-e has good diagnostic performance when compared with other techniques commonly used for the diagnosis of bowel endometriosis such as transvaginal ultrasonography, rectal water contrast transvaginal ultrasonography, and magnetic resonance imaging. MDCT-e is usually well tolerated by the patients. However, this technique has two major limitations: the exposure to radiation and the administration of iodinated constraint medium to young women of reproductive age suffering a benign condition. In conclusion, MDCT-e has high diagnostic performance for rectosigmoid and other bowel endometriosis. It allows to reliably rule out the diagnosis with a negative result and to rule in the diagnosis with a positive result.

Recent discussions in the literature, along with the revision of the Diagnostic and Statistical Manual (DSM) [2], suggest aetiological commonalities between the highly comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Addressing this discussion requires studying these disorders together by comparing constructs typical to each of them. In the present study, we investigate global processing, known to be difficult for participants with ASD, and Intra-Subject Variability (ISV), known to be consistently increased in participants with ADHD, in groups, aged 10-13 years, with ADHD (n=25), ASD without comorbid ADHD (ASD-) (n=13) and ASD with ADHD (ASD+) (n=18) in comparison with a typically developing group (n=22). A Copying task, typically requiring global processing and in this case particularly designed using equally complex stimuli to also measure ISV across trials, was selected. Oculomotor measures in this task proved to be particularly sensitive to group differences. While increased ISV was not observed in the present task in participants with ADHD, both ASD groups needed to look longer on the figure to be drawn, indicating that global processing takes longer in ASD. However, the ASD+ group needed to fixate on the figure only between drawing movements, whereas the ASD-group needed to do this throughout the drawing process. The present study provides evidence towards ASD and ADHD being separate, not-overlapping, disorders. Since the pure ASD-group was affected more by central coherence problems than the ASD+ group, it may suggest that neuropsychological constructs interact differently in different clinical groups and sub-groups.

The aim of this chapter is to introduce the role of computed tomography colonoscopy (CTC) for the diagnosis of bowel endometriosis. CTC provides accurate information on the characteristic of endometriotic intestinal nodule and precisely assess the distance between its localization and the anal verge. A further relevant advantage of this radiologic exam is that it provides an overview of the whole colon and, in particular, of the intestinal nodules which are located above the sigmoid colon. Considering that in 39% of cases bowel lesions are multifocal, a complete assessment of the colon is essential to detect all endometriotic lesions before surgery; in fact, multiple endometriotic nodules on the digestive tract may require multiple segmental bowel resections or disc excisions. CTC is a quick outpatient exam with high spatial resolution, and it allows scanning the abdomen within seconds; moreover, it is safe and minimally painful for the patients, not requiring analgesia or sedation. Colonic distension with CO2 and combination of prone and supine positions provide better estimation of digestive tract narrowness than that of any other imaging techniques. However, CTC should not be considered as an alternative to TVS or MRI, because these imaging techniques provide a better assessment of deep pelvic endometriosis, ovarian endometriomas, and uterine adenomyosis.

Intra-Subject Variability (ISV), a potential index of catecholaminergic regulation, is elevated in several disorders linked with altered dopamine function. ISV has typically been defined as reaction time standard deviation. However, the ex-Gaussian and spectral measures capture different aspects and may delineate different underlying sources of ISV; thus reflecting different facets of the construct. We examined the impact of factors associated with dopamine metabolism, namely, Catechol-O-Methyltransferase Val158Met (COMT) genotype and Working Memory (WM) and response-switching on ISV facets in young healthy adults. The Met allele was associated with overall increased variability. The rather exclusive sensitivity of ex-Gaussian tau to frequencies below 0.025 Hz and the quasi-periodic structure of particularly slow responses support the interpretation of tau as low frequency fluctuations of neuronal networks. Sigma, by contrast, may reflect neural noise. Regarding cognitive demands, a WM load-related increase in variability was present for all genotypes and all ISV facets. Contrastingly, ISV facets reacted differently to variations in response-switching as, across genotypes, sigma was elevated for rare target trials whereas tau was elevated for frequent standard trials, particularly for Met homozygotes. Our findings support the significant role of COMT in regulating behavioural ISV with its facetted structure and presumed underlying neural processes.

Lombardy was the first area in Italy to have an outbreak of coronavirus disease 19 (COVID-19) at the beginning of 2020. In this context, cancer has been reported as a major risk factor for adverse outcomes and death, so oncology societies have quickly released guidelines on cancer care during the pandemic. The aim of this study was to investigate the management of cancer patients and oncological treatments during the COVID-19 pandemic and to describe the containment measures performed in our outpatient clinic at Pavia (Lombardy). A comparison with the same period of the four previous years (2019, 2018, 2017, and 2016) was also performed. Using our electronic databases, we evaluated the number and characteristics of patients accessing the hospital for anticancer drug infusion from 24 February, 2020 to 30 April, 2020 and the number of radiological exams performed. Although a significant reduction in access for therapy was seen when compared with 2019 (2590 versus 2974, access rate ratio (ARR) = 0.85, p &lt, 0.001), no significant differences in access numbers and ARR was evident between 2020 and 2018, 2017, or 2016 (2590 versus 2626 (ARR = 0.07), 2660 (ARR = 0.99), and 2694 (ARR = 0.96), respectively, p &gt, 0.05). In 2020, 63 patients delayed treatment: 38% for &ldquo, pandemic fear&rdquo, 18% for travel restrictions, 13% for quarantine, 18% for flu syndrome other than COVID-19, and 13% for worsening of clinical conditions and death. Only 7/469 patients developed COVID-19. A significant reduction in radiological exams was found in 2020 versus all the other years considered (211 versus 360, 355, 385, 390 for the years 2020, 2019, 2018, 2017, and 2016, respectively, p &lt, 0.001). The low incidence of COVID-19 among our cancer patients, along with the hospital policy to control infection, enabled safe cancer treatment and a continuum of care in most patients, while a small fraction of patients experienced a therapeutic delay due to patient-related reasons.

Using a schema-theoretical perspective in the field of moral cognition, we assessed response behavior of adolescent (n = 15) and adult (n = 22) individuals with Autism Spectrum Disorder (ASD) in comparison with adolescent (n = 22) and adult (n = 22) neurotypically developed controls. We conceptualized the Intuitive Moral Reasoning Test—in five moral dilemmas, participants had to choose between two alternative actions and assess their decision with respect to emotional valence, arousal, moral acceptability and permissibility from both the perspective of the acting person and then of the victim. Patients with ASD displayed a different decision and response behavior, particularly when the dilemmas were based on extreme life situations in combination with a social schema involving close social relationships.

The recording of eye movements is a unique method in the study of development in typical and atypical populations that has gained much valuable knowledge over the decades of its application. In the first part of this chapter, we question why and how we can, or should, study developmental processes, what eye movement recordings have taught us about the typical cognitive development. Moreover, we discuss the strengths and limitations of the paradigms that have been used here. Specifically, we introduce how eye movements reveal what newborns are able to discriminate and what this tells us about their early mental abilities and individual differences herein. We also outline how visual attention, closely linked to the orientation of our gaze, develops from infancy onwards. We furthermore explain the development of major eye movement types such as smooth pursuit eye movements, visually-guided saccades and saccades that are voluntarily generated such as those that bring the gaze to a remembered or instructed position in space. We also look at global and local stimulus processing and how that differentiation develops in childhood and adolescence. Finally, we take a closer look at how face processing—as investigated with eye movement recordings—develops and how we use our eye to track occluded objects. In the second part of this chapter, we will provide a definition of “atypical development”, explain and discuss the paradigms that have been employed to study atypical development in psychiatric disorders of childhood and adolescence and what has been found in disorders such as autism, attention-deficit hyperactivity disorder, reading disorders and early onset schizophrenia.

(1) Objectives: In patients with symptoms suggestive of rectosigmoid endometriosis, imaging techniques are required to confirm the presence and establish the extent of the disease. The objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography (3D-RWC-TVS) and computed tomographic colonography (CTC) in predicting the presence and characteristics of rectosigmoid endometriosis. (2) Methods: This prospective study included patients with suspicion of rectosigmoid endometriosis who underwent both 3D-RWC-TVS and CTC and subsequently were surgically treated. The findings of imaging techniques were compared with surgical and histological results. (3) Results: Out of 68 women included in the study, 37 (48.9, 95% C.I. 38.2&ndash, 59.7%) had rectosigmoid nodules and underwent bowel surgery. There was no significant difference in the accuracy of 3D-RWC-TVS and CTC in diagnosing the presence of rectosigmoid endometriotic nodules (p = 0.118), although CTC was more precise in diagnosing endometriosis located in the sigmoid (p = 0.016). 3D-RWC-TVS and CTC had similar precision in estimating the largest diameter of the main endometriotic nodule (p = 0.099) and, in patients undergoing segmental resection, the degree of the stenosis of the bowel lumen (p = 0.293). CTC was more accurate in estimating the distance between the lower margin of the intestinal nodule and the anal verge (p = 0.030) but was less tolerated than 3D-RWC-TVS (p &lt, 0.001). (4) Conclusion: This was the first study comparing the performance of 3D-RWC-TVS and CTC in the diagnosis of rectosigmoid endometriosis. Both techniques allowed for the evaluation of the profile of the bowel lumen in a pseudoendoscopic fashion and had a similar performance for the diagnosis of rectosigmoid endometriosis, although CTC was more accurate in diagnosing and characterizing sigmoid nodules.

MotivationComplex neuropsychiatric conditions including autism spectrum disorders are among the most heritable neurodevelopmental disorders with distinct profiles of neuropsychological traits. A variety of genetic factors modulate these traits (phenotypes) underlying clinical diagnoses. To explore the associations between genetic factors and phenotypes, genome-wide association studies are broadly applied. Stringent quality checks and thorough downstream analyses for in-depth interpretation of the associations are an indispensable prerequisite. However, in the area of neuropsychology there is no framework existing, which besides performing association studies also affiliates genetic variants at the brain and gene network level within a single framework.ResultsWe present a novel bioinformatics approach in the field of neuropsychology that integrates current state-of-the-art tools, algorithms and brain transcriptome data to elaborate the association of phenotype and genotype data. The integration of transcriptome data gives an advantage over the existing pipelines by directly translating genetic associations to brain regions and developmental patterns. Based on our data integrative approach, we identify genetic variants associated with Intelligence Quotient (IQ) in an autism cohort and found their respective genes to be expressed in specific brain areas.ConclusionOur data integrative approach revealed that IQ is related to early down-regulated and late up-regulated gene modules implicated in frontal cortex and striatum, respectively. Besides identifying new gene associations with IQ we also provide a proof of concept, as several of the identified genes in our analysis are candidate genes related to intelligence in autism, intellectual disability, and Alzheimer’s disease. The framework provides a complete extensive analysis starting from a phenotypic trait data to its association at specific brain areas at vulnerable time points within a timespan of four days.Availability and ImplementationOur framework is implemented in R and Python. It is available as an in-house script, which can be provided on demand.Contactafsheen.yousaf@kgu.de

BACKGROUND Therapeutic drug monitoring is becoming increasingly important in psychiatric therapy, especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, noninvasive procedures, blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects and to analyze intraindividual variation of serum concentration. METHODS Thirty-six patients with ADHD (27 children and 9 adults) on MPH medication were included for drug analysis. MPH and its major metabolite ritalinic acid were quantified using liquid chromatography-tandem mass spectrometry measurements. The following correlations were investigated: (1) between drug concentrations in serum and saliva, and (2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed. RESULTS After quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, whereas the concentrations of ritalinic acid were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r = 0.51, P < 0.05). Saliva MPH measures, compared with serum, were pH-dependent (r = -0.56, P < 0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%-42%), whereas the coefficient of variance for the ratio of saliva to serum was 122% (2%-2060%). CONCLUSIONS Our data indicate that the interindividual variation in saliva to serum concentrations is rather high, whereas the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for therapeutic drug monitoring of MPH in patients with ADHD, especially for follow-up examinations. Future research should focus on analyzing the relationship between drug levels in saliva and clinical effects as well as on understanding the mechanisms that generate saliva drug concentrations. These are essential steps before potential clinical use.

Planning impairment is often observed in children with high-functioning autism spectrum disorders (ASD), but attempts to differentiate planning in ASD from children with attention deficit hyperactivity disorder (ADHD) and typically developing children (TD) have yielded inconsistent results. This study examined differences between these groups by focusing on development and analyzing performance in searching ahead several steps ("search depth") in addition to commonly used global performance measures in planning. A cross-sectional consecutive sample of 83 male patients (6-13 years), subgrouped as ASD without (ASD-, n = 18) or with comorbid ADHD (ASD+, n = 23), ADHD only (n = 42) and n = 42 TD children (6-13 years) were tested with the Tower-of-London-task. For global performance, ASD+ showed the lowest accuracy in younger children, but similar performance as TD at older ages, suggesting delayed development. Typically, a prolongation of planning time with increasing problem difficulty is observed in older children as compared to younger children. Here, this was most pronounced in ASD-, but under-expressed in ADHD. In contrast to global performance, effects of search depth were independent of age. ASD-, but not ASD+, showed increased susceptibility to raised demands on mentally searching ahead, along with the longest planning times. Thus, examining both global and search depth performance across ages revealed discernible patterns of planning between groups. Notably, the potentially detrimental impact of two diagnosed disorders does not add up in ASD+ in this task. Rather, our results suggest paradoxical enhancement of performance, ostensibly attributable to disruption of behavioral rigidity through increased impulsivity, which did not take place in ASD-. Autism Res 2016, 9: 739-751. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Background The ureter is the second most common site affected by urinary tract endometriosis, after the bladder. Optimal strategies in the diagnosis and treatment of ureteral endometriosis (UE) are not yet well defined. Objective and rationale The aim of this study was to systematically review evidence regarding the epidemiology, pathophysiology, diagnosis, medical and surgical treatment, impact on fertility and risk of malignant transformation of UE. Search methods A systematic literature review, by searching the MEDLINE and PUBMED database until April 2018, was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/PROSPERO CRD42017060065). A total of 67 articles were selected to be included in this review. Outcomes The involvement of the ureter by endometriosis is often asymptomatic or leads to non-specific symptoms. When the diagnosis is delayed, UE may lead to persistent hydronephrosis and eventually loss of renal function. Ultrasonography is the first-line technique for the assessment of UE; alternatively, magnetic resonance imaging provides an evaluation of ureteral type involvement. The surgical treatment of UE aims to relieve ureteral obstruction and avoid disease recurrence. It includes conservative ureterolysis or radical approaches, such as ureterectomy with end-to-end anastomosis or ureteroneocystostomy performed in relation to the type of ureteral involvement. Fertility and pregnancy outcomes are in line with those observed after surgical treatment of deep infiltrating endometriosis (DIE). Current evidence does not support the potential risk of malignant transformation of UE. Wider implications In this article, we review available evidence on ureteral endometriosis, providing a useful tool to guide physicians in the management of this disease. Diagnosis and management of UE remain a challenge. In relation to the degree of ureteral involvement and the association with other DIE implants, the surgical approach should be planned and carried out in an interdisciplinary collaboration between gynecologist and urologist.

Background Increased intra-subject variability (ISV) in reaction times (RTs) is a promising endophenotype for attention-deficit hyperactivity disorder (ADHD) and among the most robust hallmarks of the disorder. ISV has been assumed to represent an attentional deficit, either reflecting lapses in attention or increased neural noise. Here, we use an innovative single-trial event-related potential approach to assess whether the increased ISV associated with ADHD is indeed attributable to attention, or whether it is related to response-related processing. Methods We measured electroencephalographic responses to working memory oddball tasks in patients with ADHD (N = 20, aged 11.3 ± 1.1) and healthy controls (N = 25, aged 11.7 ± 1.1), and analysed these data with a recently developed method of single-trial event-related potential analysis. Estimates of component latency variability were computed for the stimulus-locked and response-locked forms of the P3b and the lateralised readiness potential (LRP). Results ADHD patients showed significantly increased ISV in behavioural ISV. This increased ISV was paralleled by an increase in variability in response-locked event-related potential latencies, while variability in stimulus-locked latencies was equivalent between groups. This result held across the P3b and LRP. Latency of all components predicted RTs on a single-trial basis, confirming that all were relevant for speed of processing. Conclusions These data suggest that the increased ISV found in ADHD could be associated with response-end, rather than stimulus-end processes, in contrast to prevailing conceptions about the endophenotype. This mental chronometric approach may also be useful for exploring whether the existing lack of specificity of ISV to particular psychiatric conditions can be improved upon.

Adenomyosis is a gynecologic disorder characterized by the presence of ectopic endometrial tissue within the uterine myometrium. It can involve most of the myometrium (diffuse adenomyosis), it may be present only in a circumscribed part of the myometrium (focal adenomyosis) or it may appear as a large cyst (adenomyotic cyst). The common sign of adenomyosis is uterine enlargement.

The objective of our prospective monocentric work was to determine the diagnostic value of real-time elastography (RTE) in the assessment of liver fibrosis in patients with iron overload, using transient elastography (TE) as reference standard.Sixty-seven consecutive patients with MRI detectable iron overload (T2*6.3 ms) were enrolled. TE and RTE were performed on the same day as MRI. Elastograms were acquired by an experienced operator and analyzed by calculating the elastic ratio between perihepatic soft tissues and liver parenchyma. An elliptical ROI of 1cm(2) (Z1) was positioned in the liver parenchyma and a smaller elliptical ROI of 2mm(2) (Z2) was positioned in a homogeneously soft (red) region of the diaphragm, which was considered as internal control to calculate the elastic ratio Z2/Z1.Seven patients were excluded because of invalid TE or RTE examinations. The remaining 60 patients were 57% males and 43% females (mean age: 42 [21-76] years), including 37 homozygous-β-thalassemics, 13 patients with β-thalassemia intermedia, 6 with primary hemochromatosis, and 4 with myelodysplastic syndrome. Increasing elastic ratios were significantly correlated with increasing TE values (r=0.645, 95% CI 0.468-0.772, P0.0001). The mean elastic ratios for each METAVIR group were as follows: F0/1 = 1.9 ± 0.4; F2 = 2.2 ± 0.4; F3 = 2.9 ± 0.5; F4 = 3.2 ± 0.4. The diagnostic accuracy of RTE for F ≥ 2 evaluated by AUC-ROC analysis was 0.798 (95% CI 0.674-0.890). The diagnostic accuracy of RTE for F ≥ 3 was 0.909 (95% CI 0.806-0.968). At a cut-off ≥ 2.75, RTE showed a sensitivity of 70% (95% CI 45.7-88.1) and a specificity of 97.5% (95% CI 86.8-99.9).In patients with MRI-detectable liver iron-overload RTE allows to discriminate between F0/1-F2 and F3-F4 with a reasonable diagnostic accuracy.

The co-occurrence of motor and imitation disabilities often characterises the spectrum of deficits seen in patients with autism spectrum disorders (ASD). Whether these seemingly separate deficits are inter-related and whether, in particular, motor deficits contribute to the expression of imitation deficits is the topic of the present study and was investigated by comparing these deficits' cross-sectional developmental trajectories. To that end, different components of motor performance assessed in the Zurich Neuromotor Assessment and imitation abilities for facial movements and non-meaningful gestures were tested in 70 subjects (aged 6-29 years), including 36 patients with high-functioning ASD and 34 age-matched typically developed (TD) participants. The results show robust deficits in probands with ASD in timed motor performance and in the quality of movement, which are all independent of age, with one exception. Only diadochokinesis improves moderately with increasing age in ASD probands. Imitation of facial movements and of non-meaningful hand, finger, hand finger gestures not related to social context or tool use is also impaired in ASD subjects, but in contrast to motor performance this deficit overall improves with age. A general imitation factor, extracted from the highly inter-correlated imitation tests, is differentially correlated with components of neuromotor performance in ASD and TD participants. By developmentally fractionating developmentally stable motor deficits from developmentally dynamic imitation deficits, we infer that imitation deficits are primarily cognitive in nature.

Objective To investigate spontaneous pregnancy rate (SPRs) of women with rectovaginal endometriosis (RV) with/without ovarian endometrioma (OMA) and treated with the use of expectant or surgical management. Design Retrospective study. Setting University hospital. Patient(s) The study included patients with RV with or without OMA who tried to conceive spontaneously for 1 year either without undergoing surgery (group E; n=284) or after surgery (group S; n=221). The study population was further divided into four subgroups: women with RV without OMA who directly tried to conceive (group eRV; n=121) or tried to conceive after surgery (group sRV; n=96), and women with RV with OMA who directly tried to conceive (group eOMA; n=163) or tried to conceive after surgery (group sOMA; n=125). Interventions(s) Expectant or surgical management. Main Outcome Measure(s) Crude and cumulative SPRs. Result(s) At 1 year, crude and cumulative SPRs were lower in group E (17.3% and 23.8%, respectively) than in group S (35.7% and 39.5%). Similarly, crude and cumulative SPRs were lower in group eRV (24.8% and 30.6%) than in group sRV (42.7% and 45.7%, respectively) and in group eOMA (11.7% and 18.0%) than group sOMA (30.4% and 34.5%). At 1 year, crude and cumulative SPRs were higher in group eRV (24.8% and 30.6%) than in group eOMA (11.7% and 18.0%), and in group sRV (42.7% and 45.7%) than in group sOMA (30.4% and 34.5%). Conclusion(s) Crude and cumulative SPRs are lower in women treated with the use of expectant rather than surgical management. The presence of OMAs decreases SPRs independently from the treatment modality adopted.

To study the efficacy of long-term treatment with norethindrone acetate (NETA) in patients with rectovaginal endometriosis.This retrospective cohort study included 103 women with pain symptoms caused by rectovaginal endometriosis. Patients received NETA alone (2.5mg/day up to 5mg/day) for 5 years. Primary outcome was the degree of satisfaction with treatment after 5 years of progestin therapy. Secondary outcomes were the assessment of any variation in pain symptoms and the volumetric assessment of the disease by magnetic resonance imaging (MRI).Sixty-one women completed the 5-year follow-up (61/103, 59.2%) with 16 women withdrawing because of adverse effects (38.1%). Overall, 68.8% (42/61) of the women who completed the study were satisfied or very satisfied of this long term NETA treatment. This represents a 40.8% (42/103) of the patients enrolled. Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (p0.001 versus baseline at 1 and 5year). Dyschezia improved after 1-year respect to baseline (p=0.008) but remained stable between first and second year (p=0.409). At the end of 5 years treatment, a radiological partial response was observed in 33 patients (55.9%, n 33/59); a stable disease in 19 patients (32.2%, n 19/59). Seven women (7/59, 11.9%) displayed a volumetric increase of rectovaginal endometriosis under NETA treatment.Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological profile, it represents a good candidate for long-term treatment in this setting.

BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro–brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS: Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs (P= .03 and P= .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS: Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.

Aim We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). Method PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS25) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17y 11mo, SD 4y 5mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22y 4mo, SD 5y 2mo). The amplitude of motor-evoked potentials was measured before PAS25, immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PASN20+2) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. Results In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS25. This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Interpretation Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients.

Purpose So far, no studies comparing 18 F-Fluoride-PET/CT and MDCT for the detection of bone metastases are available. We compared the accuracy of 18 F-Fluoride-PET/CT (MDCT: 3.75 mm thickness-image-reconstruction), whole-body Multi-Detector-CT (MDCT: 1.25 mm thickness-image-reconstruction) and 18 F-Fluoride-PET/MDCT (MDCT: 1.25 mm thickness-image-reconstruction) in identifying bone metastases in breast cancer patients. Methods We studied 39 breast cancer patients for bone metastases. Imaging was performed on an integrated PET/MDCT-system; CT images were reconstructed at 3.75 mm and 1.25 mm thickness. Two nuclear medicine physicians and one radiologist interpreted blindly 18 F-Fluoride-PET/CT, 18 F-Fluoride-PET/MDCT and MDCT. MDCT at 12 months served as the standard of reference. Results Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference. 18 F-Fluoride-PET/CT detected 491 bone metastases, 114 (23%) of which displayed no clear morphological changes on MDCT, whereas MDCT detected 416 bone metastases, 39 (9.3%) of which showed no 18 F-Fluoride-PET uptake. Overall sensitivity and specificity were: 91% and 91%, respectively, for 18 F-Fluoride-PET/CT, and 77% and 93% for MDCT. The integrated assessment of 18 F-Fluoride-PET/MDCT yielded sensitivity and specificity values of 98% and 93%, respectively. Conclusions 18 F-Fluoride-PET/MDCT has higher diagnostic accuracy than 18 F-Fluoride-PET/CT and MDCT for the evaluation of bone metastases in breast cancer.

Computed tomography enterography (CTE) may detect the presence, severity, and extent of bowel inflammation in patients with Crohn's disease (CD). The aim of our study was to assess, among a cohort of 22 histologically proven CD patients, the prevalence of disease distribution, behavior, anastomotic recurrence and extraintestinal manifestations detected by an original CTE technique.Two radiologists reviewed 221 CTEs performed providing both small and large bowel distension by oral administration of neutral contrast material and trans-rectal introduction of a water enema (CTE-WE).Ileal CD was detected in 116 CTE-WEs (52.4%), including 71/116 (61.2%) non-stricturing/non-penetrating, 17/116 (14.6%) stricturing, and 28/116 (24.1%) penetrating forms. Colonic CD was appreciable in 35 (15.8%) patients, including 18/35 (51.4%) non-stricturing/non-penetrating, 6/35 (17.1%) stricturing, and 11/35 (31.4%) penetrating forms. Ileocolic CD was present in 52 (23.5%) CTE-WEs, including 30/52 (57.7%) non-stricturing/ non-penetrating; 3/52 (5.7%) stricturing, and 19/52 (36.5%) penetrating forms. In 10/221 patients (4.5%), upper gastrointestinal involvement (UGI) was present. Perianal disease was observed in 17/221 patients (7.7%). Fistulas were present in 52 (23.5%) and abscesses in 24 (10.8%) CTE-WEs, respectively. Among 57/221 (25.8%) patients who had undergone a disease-related intestinal resection, in 30/57 cases (52.6%) CD recurrence at the anastomosis was present. 4/221 patients (1.8%) with a histologically confirmed intestinal neoplastic stenosis were observed. Sacroiliitis (24%) was found to be prevalent over hepatic steatosis (10.8%), cholelithiasis (8.6%), and nephrolithiasis (4%).CTE-WE represents a comprehensive imaging technique which may demonstrate bowel inflammation and CD extraintestinal manifestations. A peculiar prevalence of UGI involvement and neoplastic strictures were observed. In our study the prevalence of sacroiliitis resulted higher than previously reported.

Background: Bone scintigraphy (BS) have been shown to be of value in detecting bone metastases several months before conventional radiography, whereas computed tomography (HRCT) and magnetic resonance imaging (MRI) can reveal more metastases in the spine than conventional BS. 18F-Fluoride PET has been shown to be more accurate than BS for the detection bone lesions in different malignancies and has been suggested as an alternative to BS. Recent studies have shown that integrated 18F-Fluoride-PET/CT is both sensitive and specific for detection of lytic and sclerotic lesions and is superior to 18F-Fluoride PET. The aim of our study is to evaluate the diagnostic accuracy of 18F-Fluoride-PET/CT in comparison to HRCT for the detection of bone metastases in breast cancer patients. Material and methods: The study involved 39 patients with breast cancer with known bone metastases or at high risk for its presence. All patients presented indications for skeletal surveys. Imaging was performed on an integrated PET/CT system. All PET scans were acquired in 2D mode and were reconstructed using an iterative reconstruction algorithm; diagnostic HRCT data of PET/CT were acquired for detecting bone lesions and were used for attenuation correction. PET acquisition started 60 min after intravenous injection of 370-550 MBq 18F-labelled NaF and included 10-12 bed positions. The interpretation of PET/CT and High resolution CT studies was made as a consensus reading of two nuclear medicine physicians and a radiologist who had access to clinical, as well as previous radiological imaging information. 12 months follow-up based on previous and/or following imaging studies was considered the gold standard. Results: Overall 671 bone lesions were detected in our analysis including both PET/CT and CT results. Of these lesions 530 malignant, 32 equivocal and 109 benign were classified by consensus reading. 18F-Fluoride PET/CT detected 491 bone metastases, 114 (23%) of which without any clear morphological changes on CT. HRCT detected 416 bone metastases, 39 (9.3%) of which without any 18F-fluoride uptake. The overall sensitivity and specificity was 90% and 91% for 18F-Fluoride-PET/CT and 79 and 93% for HRCT, respectively. In a patients based analysis both 18F-Fluoride-PET/CT and HRCT identified the same number of patients with bone metastases (27 of 39). Conclusions: Our data show a high agreement (71% of lesions and 100% of the patients) between 18F-Fluoride-PET/CT and HRCT for bone metastases detection. However integrated analysis of 18F-Fluoride-PET/HRCT has the best diagnostic option to evaluate bone involvement in breast cancer, and 18F-Fluoride-PET/CT seems to have the highest sensitivity. Follow-up is ongoing to assess the prognostic/predictive value of 18F-Fluoride-PET/CT. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-05-01.

There is an increase in awareness in professionals that the Asperger syndrome (AS) in adulthood is associated with specific problems and burdens which may well differ from those in childhood and adolescence. The core symptoms of AS generally persist into adulthood, however in contrast to childhood and adolescence there is no specific support system for adults in Germany. Also the environment of the afflicted patient changes thus producing different challenges and problems. In addition a subgroup of patients with high functioning AS primarily presents in adulthood generally due to secondary psychosocial problems, depression or anxiety. Difficulties in social interaction, problems with modified daily routines and unforeseen situations cause severe frustration for the majority of the patients. While several therapy programs have been developed and implemented for children and adolescents, for adults there are none. Also there is a lack of comprehensive concepts addressing the specific needs of adult patients with AS. From an economic perspective this is particularly unfortunate since affected people often have good or excellent partial abilities and might be very valuable employees. In this article existing therapeutic concepts for AS are summarized and a newly designed group therapy program for adult patients with Asperger syndrome in Freiburg is introduced (Freiburg Asperger-spezifische Therapie fur Erwachsene, FASTER) which specifically addresses the needs and problems of adult patients with AS.

Background This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. Methods This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. Results Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. Conclusions In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD.

This paper examines the diagnostic potential of multislice computed tomography enteroclysis (MSCT-E) to detect and assess different diseases affecting the small bowel, emphasising the increasingly important role assumed by the technique in the study of this anatomical region. After a short summary of the technical aspects, we discuss the different findings that can be observed during an MSCT-E study and that enable detection of small-bowel disease and, if necessary, assessment of the extent and stage of disease.

Background Common single nucleotide polymorphisms (SNPs) explain around 50% of genetic risk underlying Autism-Spectrum-Disorder (ASD). In a previous study we showed that common functional SNPs of genes implicated in Fragile X Syndrome (FXS) were associated with ASD (Waltes et al., 2014). The FXS associated protein FMRP is regulated by the glutamatergic system, a patho-mechanism discussed for ASD. Objective We tested if functional common SNPs of glutamatergic genes were associated with ASD or ASD specific symptoms in two large ASD family cohorts (Autism Genome Project/AGP set, N=2734 families; German data set N=578 families). Since the genetic architecture between individuals with High IQ (HIQ= IQ>70) and Low IQ (LIQ= IQ≤70) differs (Vieland et al., 2010), we also split the two cohorts into high and low functioning (HIQ, LIQ) individuals. Methods 207 functional SNPs of 124 glutamatergic genes with a minor allele frequency over 5% were tested using Plink v 1.9 (DFAM) in the cohort with HIQ, LIQ and the combined cohorts, respectively. Phenotype association was studied by logistic ordinal regression correcting for gender, IQ, clinical site and population stratification. Phenotype measures were taken from the Autism Diagnostic Interview-Revised (ADI-R) scores for Social Interaction (Domain A), Verbal Communication (B1-B4; verbal individuals only), Non-Verbal Communication (Domain B2; B3; all individuals) and Repetitive Behavior (Domain C). Variants significant in both cohorts with effect sizes in the same direction were considered as replicated. Similarly, genes with any nominal significant variant in both cohorts were considered as replicated hits. Results We identified nominal significant associations of variants rs7206796 and rs3790112 (GNAO1) as well as rs3742926 (AKAP6) in both the German and the AGP LIQ cohort. In addition, significant but not overlapping SNPs of AKAP2 were identified (LIQ only). rs731826 (AKT1S1) was associated with Non Verbal Communication in the HIQ cohorts. In addition, we report 24 variants that were nominally associated with ADI-R scores in both cohorts. Genes that were involved in all five phenotypes tested were strongly related to the mTOR Pathway (e.g. genes MTOR and TSC2) or the second messenger system (e.g. G-proteins GNAS, phospholipases PLCB, protein phosphatases PPP1CA). A subset of genes was specific to each phenotype or significant in one of the subgroups (HIQ and LIQ) only. For example AKAP13 or RPS6K are associated with Verbal Communication in Low Functioning Individuals. Discussion Replication and extending previous findings we found that variants of genes that are associated with glutamate signaling, and specifically the mTOR pathway are modulators of ASD symptoms. Genes such as TSC1 or RPS6K are known to mediate glutamatergic signaling through mTOR, whereas AKAP proteins are important interactors of glutamate receptors (Sanderson et al., 2011). Both, the mTOR pathways and AKAP proteins have previously been associated with ASD (Chen et al ., 2014; Poelmans et al., 2013). Further functional analyses of glutamatergic variants are thus recommended to elucidate ASD etiology.

Background Autism spectrum disorders (ASD) are a group of genetically and phenotypically heterogeneous neurodevelopmental disorders. Common genetic variants are currently estimated to account for over 50% of ASD liability, and are also suggested to contribute to phenotypic variability. Only few studies have reported association of genetic variants with quantitative ASD phenotypes and it is unclear if different phenotypic aspects of the disorder have a distinct etiology. Here, we aim at discovering associations of common variants with ASD related phenotypes. To interpret the findings in their biological context we mapped significant variants to their genes and tested for enriched pathways and networks implicated in brain development. Methods We investigated phenotype and genotype data of 637 German trios with ASD and of the Autism Genome Project cohort (2004 families). Both cohorts were harmonized and quality checked at phenotypic (Autism Diagnostic Interview Revised, ADI-R items) and genotypic (Illumina Microarrays) level. We performed factor analysis of 28 single items of the ADI-R used in the diagnostic algorithm. To increase genetic resolution and the number of overlapping variants between the two datasets we imputed common variants with a MAF>0.05 using the “1000 Genomes” data as reference. SNPs significantly associated with the phenotype were identified using regression models corrected for ancestry, gender and IQ. Significant variants identified in both, the German and the AGP cohort, were subjected to GO-term, KEGG, and pathway enrichment analysis. Gene-regulatory modules implicated in brain development were defined by weighted gene co-expression analysis using publicly available transcriptome data of the developing human brain (brainspan.org) and tested for enrichment with the associated gene sets. Results We extracted 5 factors of the ADI-R items labeled as joint attention, social interaction and communication, non-verbal communication, repetitive sensory-motor behavior and compulsion and restricted interests. Of the 7.5M variants with a MAF > 0.05 available after imputation and quality check over 500 were associated nominally significant and replicated with each factor respectively. Analysis of the underlying genes showed that the associated GO-terms were specific for each factor and reflected directly linked biological processes such “sensory processing” for repetitive sensory-motor behavior. Finally, we present developmental time-frames specifically enriched for associated gene-sets. Discussion Our findings suggest that each ASD related phenotype is underlying a specific genetic etiology. The identification of critical periods during development further allows understanding the effects of genetic variants at specific brain-developmental and brain-regional networks. These findings thus provided a deeper insight into the complex genetic architecture of ASD and increased our understanding of mechanisms modulating ASD phenotypes