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Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).

Background and aim Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of trophoblastic tissue. Since GTD and its malignant sequel gestational trophoblastic neoplasia (GTN) are rare diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. Methods Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid trophoblastic tumours and follow-up. Results Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. Conclusions Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device-based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty-seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device-based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.

Background and aims This study aimed to evaluate whether there is a difference in human papillomavirus (HPV), smear, and cervical biopsy results between patients with and without diabetes mellitus (DM). Methods Retrospectively, 136 patients with positive high risk (HR) HPV screening results with and without DM who underwent colposcopy between 2015 and 2019 were identified. The clinicopathological characteristics and HR HPV screening results were reported and analyzed. The results of the patients with and without DM were compared. Results HPV 16 positivity, Atypical Squamous Cells of Undetermined Significance (ASCUS), and Cervical Intraepithelial Neoplasia 1 (CIN 1) in smear and biopsy results were higher in patients with DM than patients without DM. Conclusions The higher HPV positivity in patients with diabetes may require reforming the frequency and method of cervical cancer screening to be applied to this patient group.

An ideal dressing should ensure that the wound remains moist with exudates but not macerated. Currently, there is no dressing available to suit all wounds, at all stages of the healing process. Although silver-containing dressings are the gold standard for burn wound care, few high-level trials have been completed comparing the clinical utilities of these dressings. In our study, five different types of wound dressings: carboxymethyl cellulose hydrofiber dressing with ionized silver (CMCH-Ag), polyethylene-polyethylene terephthalate aqua fiber dressing with elementary silver (PPAF-Ag), calcium alginate (CA), calcium + zinc alginate (CZA), and 0.2% nitrofurazone-embedded (NF) gauze dressings were compared in regard to histopathological parameters. Children aged between 0 and 18 years with small or middle-sized partial-thickness burns that affected less than 30% of the total body surface area were included in this study. The study groups (CMCH-Ag, PPAF-Ag, CA, and CZA) and the control group (NF) were randomly attained. Wound healing was evaluated by punch biopsies on the 21st day. The thickness of the stratum corneum and the epithelium, the number of papillae, and the papillary length were calculated and compared. The histological parameters of healing, except the stratum corneum thickness, did not show any statistical significance among the groups (P > .05). The dressings that included silver, calcium, or zinc showed useful and similar effects in noninfective burn wounds when compared with nitrofurazone-only dressings. Thus, it may be concluded that silver-containing wound dressings should not be considered as the gold standard in noninfective partial-thickness burn wounds in children.

BACKGROUND Donors with drowning or asphyxiation (DA) as a mechanism of death (MOD) are considered high risk in pediatric lung transplantation. We sought to evaluate whether recipients of DA donors had negatively impacted outcomes. METHODS Pediatric recipients recorded in the United Network for Organ Sharing registry between 2000 and 2019 were included. Primary stratification was donor MOD. Propensity matching with a 1:1 ratio was performed to balance the DA and non-DA MOD donor cohorts. Cox multivariable regression was used to determine the risk-adjusted impact of donor MOD. A subanalysis of the effect of lung allocation score was also evaluated. RESULTS A total of 1016 patients underwent bilateral lung transplantation during the study period, including 888 (85.6%) from non-DA donors and 128 (14.4%) from DA donors. Survival at 90 days, 1 year, and 2 years were similar in the matched and unmatched cohorts regardless of the donor MOD. Moreover, separate risk-adjusted analysis of drowning and asphyxiated donors was similar to other MOD donors at 30 days, 1 year, and 5 years. Similar survival findings persisted regardless of pretransplant lung allocation score. Although the rates of posttransplant stroke (1.0% versus 3.1%, P = 0.04) and the length of hospital stay (19 versus 22 d, P = 0.004) were elevated in the unmatched DA MOD recipients, these differences were mitigated after propensity matching. CONCLUSIONS This study evaluated the impact of DA MOD donors in pediatric lung transplant recipients and found similar rates of complications and survival in a propensity-matched cohort. These data collectively support the consideration of DA MOD donors for use in pediatric lung transplantation.

Background: Despite significant improvement in outcomes with truncus arteriosus (TA) repair, right ventricular outflow tract (RVOT) reconstruction with a right ventricular to pulmonary artery (RV-to-PA) conduit remains a source of long-term reintervention and reoperation. This study evaluated our experience with reintervention in homograft and polytetrafluoroethylene (PTFE) RV-to-PA conduits in neonates. Methods: Primary TA repairs from 2004 to 2016 at a single institution were included. Stratification was based on RVOT reconstruction with PTFE or homograft conduit. Primary outcome was operative conduit replacement. Secondary outcomes included the rates and types of catheter-based conduit interventions. Results: Twenty-eight patients underwent primary TA repair and 89.3% (n = 25) of them had RVOT reconstruction with a homograft (28.0%, n = 7) or PTFE (72.0%, n = 18) conduit. Rates of reoperation for conduit replacement and catheter-based interventions were similar between those with PTFE and homograft conduits (85.7% vs 72.2%, P = .49 and 57.1% vs 83.3%, P = .11, respectively). Additionally, the median time to conduit replacement and catheter-based conduit interventions were comparable. In multivariable analysis, conduit size, but not conduit type, was a predictor of conduit revision (hazard ratio: 1.66, 95% confidence interval: 1.11-2.49, P = .02). At five-year and ten-year follow-up, patients with PTFE conduits had better survival than those with homograft conduits (100.0% vs 71.4%, P = .02); however, no mortalities were associated with conduit reoperations or catheter-based reinterventions. Conclusions: Polytetrafluoroethylene and homograft RVOT reconstruction in neonatal TA repair demonstrate similar durability as defined by reoperation and reintervention rates. The validation of the durability of PTFE conduits in neonatal TA repair requires confirmatory studies in larger cohorts.

Women with stress urinary incontinence (SUI) often require combined pelvic reconstructive surgeries because of shared risk factors of pelvic organ prolapse. The purpose of this study was to evaluate efficacies of Burch colposuspension, transobturator tape (TOT), and single-incision needleless (DynaMeshWe performed this retrospective cohort study that comprising 122 patients who either underwent Burch colposuspension (n:43), TOT (n:40), or SIS (n:39) procedures along with pelvic reconstructive surgery or hysterectomy between January 2010 and July 2018. During the clinical follow-up, we analyzed cure rates, and surgical success rates of SUI surgery, quality of life, and symptom severity by IIQ-7, UDI-6, SSI, SSQ-8, OAB-V8, and PGI-I scale scores. The primary outcome was surgical success, whereas secondary outcomes included complications and patient-reported outcomes in the quality of life.We found that surgical success rates were higher in Burch group than SIS group and higher in TOT group than in SIS group (88.4% vs 61.5% and 87.5% vs 61.5%, p = 0.003). The quality of life was lower in SIS group than in Burch group.Both Burch and TOT are effective procedures in patients with SUI who require additional pelvic surgeries. Although surgical outcomes of SIS procedure in patients with SUI who underwent concomitant pelvic surgeries in our study were not promising, further studies with SIS are needed to clarify these observations.

The main aim of this study is to investigate whether there are relationships between perceived partner responsiveness (PPR), co-regulation of negative affect between romantic partners and binge eating. Data were collected from 148 opposite-sex romantic partners (18-61 years old) with the mean relationship duration being 8.04 years. Dyadic data were analysed through the actor-partner interdependence model framework. We proposed a model where co-regulation between partners has indirect effects on the relationship between PPR and binge eating. Results showed that there was no direct association between PPR and binge eating scores of the participants. However, significant direct associations were found regarding both actor and partner effects of PPR on co-regulation between romantic partners. In addition, there were four significant indirect effects: Women's co-regulation had an indirect effect on the link between PPR and women's binge eating scores. Similarly, women's co-regulation had also a significant indirect effect on the link between PPR and men's binge eating. These findings are the first to illustrate a relationship between PPR and binge eating. This study is the first attempt to examine binge eating in terms of co-regulation processes. Kadir Has University School of Graduate Studies

The aim of this study was to determine the accuracy of the 24-h urine collection in preeclamptic pregnant women. This study included 65 singletons with preeclampsia and 53 singleton patients in a control-matched group. The ratio of inaccurate 24-h urine collection was measured by calculating expected urine creatinine excretion according to the proportion of pre-pregnancy weight and the lean body mass (LBM) of the patients. Comparisons were made between the accurately-collected 24-h urine protein excretion rates and the instant and 24-h urine protein/creatinine (P/Cr) and albumin/creatinine (A/Cr) ratios. Twenty-four-hour urine collection used to diagnose patients with preeclampsia was incorrectly collected 15–73.5% of the time among the patients and the control group. Instant and 24-h urine P/Cr and A/Cr ratios were correlated with total 24-h proteinuria among the patients in whom urine was collected correctly. Considering the 24-h urine P/Cr ratio, rather than the 24-h urine protein excretion value, is a better way to diagnose preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Twenty-four-hour urine collection is considered as the gold standard of diagnosing proteinuria in preeclampsia, in case of the correctly collected. What do the results of this study add? Generally, in the literature the correctness of 24-h proteinuria is not questioned. However, it is actually quite important in daily practice to make the correct diagnosis of the proteinuria not to misdiagnose preeclampsia. What are the implications of these findings for clinical practice and/or further research? In this article, we aimed to show the importance of accurately collected 24-h urine in preeclampsia. We consider and advise to change the gold standard of this technique to 24-h protein/creatinine (P/Cr) ratio, in order to make correct diagnosis of the preeclampsia. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Two of the most commonly used substances by adolescents in the United States are cannabis and alcohol. Cannabis Use Disorder (CUD) and Alcohol Use Disorder (AUD) are associated with impairments in decision-making processes. One mechanism for impaired decision-making in these individuals is thought to be an inability to adequately represent future events during decision-making. In the current study involving 112 adolescents, we used a comparative optimism task to examine the relationship between relative severity of CUD/AUD (as indexed by the CUD/AUD Identification Tests [CUDIT/AUDIT]) and atypical function within neural systems underlying affect-based neural represenation future events. Greater CUDIT scores were negatively related to responses within subgenual anterior and posterior cingulate cortex when processing high-intensity potential future positive and negative events. There was also a particularly marked negative relationship between CUD symptoms and blood oxygen level-dependent (BOLD) responses within visual and premotor cortices to high-intensity, negatively valenced potential future events. However, AUD symptom severity was not associated with dysfunction within these brain regions. These data indicate that relative risk/severity of CUD is associated with reduced responsiveness to future high-intensity events. This may impair decision-making where future significant consequences should guide response choice.

Introduction Models of attention suggest that endogenous and exogenous factors can bias attention. However, recent data suggest that reward can also enhance attention towards relevant stimulus features as a function of involuntary biases. In this study, we utilized the additional singleton task to determine the neural circuitry that biases perceptual processing as a function of reward history. Methods Participants searched for a unique shape amongst an array of differently shaped objects. All shapes, including the target shape, had the same color except one distractor shape. Participants randomly received a low or high reward after correct trials. From one trial to the next, target colors could stay the same or swap with the distractor color. Interestingly, and despite the irrelevancy of reward magnitude for task accuracy, the difference in reaction time between swap and non-swap trials usually is more pronounced following a high compared to a low reward. Results In the current study, we showed that reward modulated attention is larger for individuals with enhanced reward magnitude sensitivity in the ventral striatum. In addition, connectivity data shows that ventral striatum was more positively connected with visual cortex during high reward non-swap trials compared to high reward swap trials for participants showing stronger reward modulated attention. Conclusions This suggests that involuntary reward modulated attention might be implemented by direct influences of the ventral striatum on visual cortex.

BackgroundPrevious work has shown that amygdala responsiveness to fearful expressions is inversely related to level of callous-unemotional (CU) traits (i.e. reduced guilt and empathy) in youth with conduct problems. However, some research has suggested that the relationship between pathophysiology and CU traits may be different in those youth with significant prior trauma exposure.MethodsIn experiment 1, 72 youth with varying levels of disruptive behavior and trauma exposure performed a gender discrimination task while viewing morphed fear expressions (0, 50, 100, 150 fear) and Blood Oxygenation Level Dependent responses were recorded. In experiment 2, 66 of these youth performed the Social Goals Task, which measures self-reports of the importance of specific social goals to the participant in provoking social situations.ResultsIn experiment 1, a significant CU traits-by-trauma exposure interaction was observed within right amygdala; fear intensity-modulated amygdala responsesnegativelypredicted CU traits for those youth with low levels of trauma butpositivelypredicted CU traits for those with high levels of trauma. In experiment 2, a bootstrapped model revealed that the indirect effect of fear intensity amygdala response on social goal importance through CU traits is moderated by prior trauma exposure.ConclusionsThis study, while exploratory, indicates that the pathophysiology associated with CU traits differs in youth as a function of prior trauma exposure. These data suggest that prior trauma exposure should be considered when evaluating potential interventions for youth with high CU traits.

Alcohol and cannabis are two substances that are commonly abused by adolescents in the United States and which, when abused, are associated with negative medical and psychiatric outcomes across the lifespan. These negative psychiatric outcomes may reflect the detrimental impact of substance abuse on neural systems mediating emotion processing and executive attention. However, work indicative of this has mostly been conducted either in animal models or adults with Alcohol and/or Cannabis Use Disorder (AUD/CUD). Little work has been conducted in adolescent patients. In this study, we used the Affective Stroop task to examine the relationship in 82 adolescents between AUD and/or CUD symptom severity and the functional integrity of neural systems mediating emotional processing and executive attention. We found that AUD symptom severity was positively related to amygdala responsiveness to emotional stimuli and negatively related to responsiveness within regions implicated in executive attention and response control (i.e., dorsolateral prefrontal cortex, anterior cingulate cortex, precuneus) as a function of task performance. In contrast, CUD symptom severity was unrelated to amygdala responsiveness but positively related to responsiveness within regions including precuneus, posterior cingulate cortex, and inferior parietal lobule as a function of task performance. These data suggest differential impacts of alcohol and cannabis abuse on the adolescent brain., Highlights • Alcohol and cannabis are the most widely abused substances by adolescents. • AUDIT scores are related to amygdala hyperactivity to emotional stimuli. • AUDIT scores are related to hypoactivity in executive attention neuro-circuitry. • CUDIT scores are related to hyperactivity in executive attention neuro-circuitry.

Background: Postpartum hemorrhage (PPH) is one of the emergency situations of obstetrics practice that constitutes of 1 to 5% of vaginal and cesarean deliveries. Uterine atony is the number one cause of PPH and is responsible for at least 75% of PPH cases. Uterine compression sutures have been regarded as an effective method in PPH cases, as well as preserving fertility by preserving the uterus. Aims: The main purpose of this study was to report on our results with a new uterine compression suture technique that was developed by us. Subjects and Methods: In this study we included all women who needed uterine compression sutures because of uterine atony while cesarean section from January 2014 to December 2018. Fifteen cases with PPH with uterine atony were reported, who were treated with our uterine compression suture technique after conservative medical and uterine massage treatment failure. Results: All of the cases in this study were managed successfully namely none of the patients needed a hysterectomy or reoperation because of bleeding again. One week, one month, three months later all patients were followed up. Six months later 11 patients were examined, four patients lost to follow-up, but they were reached by phone since they were outside of the city, they reported no complaints. Ultrasound examination was performed to follow up patients. Short-term follow-up revealed no complications such as pyometra, endometritis, reoperation, amenorrhea, or uterine necrosis. Conclusions: We described our practice with our uterine compression suture that is easy to learn and apply. All of the cases that participated in our study showed improvement to the compression sutures, so no other surgical interventions were applied. The same suture technique was applied by only one physician. This is a feasible and easy way to stop bleeding in uterine atony and in uterine preservation, especially in rural areas when help may not be available in case of complications.

The present study investigates the relationship between the attachment dimensions (anxious vs. avoidance) and the cognitive performance of individuals, specifically whether the attachment dimensions would predict the working memory (WM) performance. In the n-back task, reflecting the WM capacity, both attachment related and non-attachment related words were used. Participants were randomly assigned into two groups that received either the secure or the neutral subliminal priming. In the secure priming condition, the aim was to induce sense of security by presenting secure attachment words prior to the n-back task performance. In neutral priming condition, neutral words that did not elicit sense of security were presented. Structural equation modeling revealed divergent patterns for attachment anxiety and avoidance dimensions under the different priming conditions. In neutral priming condition, WM performance declined in terms of capacity in the n-back task for individuals who rated higher levels of attachment anxiety. However in the secure priming condition, WM performance was boosted in the n-back task for individuals who rated higher levels of attachment anxiety. In other words, the subliminal priming of the security led to increased WM capacity of individuals who rated higher levels of attachment anxiety. This effect, however, was not observed for higher levels of attachment avoidance. Results are discussed along the lines of hyperactivation and deactivation strategies of the attachment system.

Deficits in reinforcement-based decision making have been reported in generalized anxiety disorder. However, the pathophysiology of these deficits is largely unknown; published studies have mainly examined adolescents, and the integrity of core functional processes underpinning decision making remains undetermined. In particular, it is unclear whether the representation of reinforcement prediction error (PE) (the difference between received and expected reinforcement) is disrupted in generalized anxiety disorder. This study addresses these issues in adults with the disorder.Forty-six unmedicated individuals with generalized anxiety disorder and 32 healthy comparison subjects group-matched on IQ, gender, and age performed a passive avoidance task while undergoing functional MRI. Data analyses were performed using a computational modeling approach.Behaviorally, individuals with generalized anxiety disorder showed impaired reinforcement-based decision making. Imaging results revealed that during feedback, individuals with generalized anxiety disorder relative to healthy subjects showed a reduced correlation between PE and activity within the ventromedial prefrontal cortex, ventral striatum, and other structures implicated in decision making. In addition, individuals with generalized anxiety disorder relative to healthy participants showed a reduced correlation between punishment PEs, but not reward PEs, and activity within the left and right lentiform nucleus/putamen.This is the first study to identify computational impairments during decision making in generalized anxiety disorder. PE signaling is significantly disrupted in individuals with the disorder and may lead to their decision-making deficits and excessive worry about everyday problems by disrupting the online updating ("reality check") of the current relationship between the expected values of current response options and the actual received rewards and punishments.

Atypical amygdala responses to emotional stimuli have been consistently reported in youth with Disruptive Behavior Disorders (DBDs; Conduct Disorder/Oppositional Defiant Disorder). However, responding to animacy stimuli has not been systematically investigated. Yet, the amygdala is known to be responsive to animacy stimuli and impairment in responsiveness to animacy information may have implications for social cognitive development. Twenty-nine youth with DBDs and 20 typically developing youth, matched for IQ, age (Mage = 14.45, SD = 2.05) and gender, completed a dot probe task during fMRI. Stimuli consisted of negative/faces, negative/objects, neutral/faces and neutral/objects images. Youth with DBDs, relative to typically developing youth, showed: i) reduced amygdala and lateral temporal cortex responses to faces relative to objects. Moreover, within the group of youth with DBDs, increasing callous-unemotional traits were associated with lesser amygdala responses to faces relative to objects. These data suggest that youth with DBDs, particularly those with high levels of CU traits exhibit dysfunction in animacy processing in the amygdala. This dysfunction may underpin the asociality reported in these youth., Highlights • Animacy processing within the amygdala is a critical component of social cognition. • Youth with DBDs had reduced responses to faces compared to objects in amygdala. • CU traits were associated with reduced amygdala responses to faces. • Youth with DBDs, particularly those with CU exhibit problems in animacy processing.

WOS: 000440567300011, PubMed ID: 29463882, Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity., Reseau Quebecois en Reproduction; McGill Faculty of Medicine; RI-MUHC Desjardins Studentship in Child Health Research; CRRD; Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR) [MOP-86546, POP-122897, MOP-130364], NMPN was supported by fellowships from Reseau Quebecois en Reproduction, McGill Faculty of Medicine, RI-MUHC Desjardins Studentship in Child Health Research, and CRRD. Yassemine Khawajkie was supported by a CRRD trainee fellowship. RS is supported by the Canadian Institute of Health Research (MOP-86546, POP-122897, and MOP-130364).

ObjectivesChronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Preventing deterioration of health status is therefore an important therapy goal. (Minimal) Clinically Important Differences ((M)CIDs) are used to interpret changes observed. It remains unclear whether (M)CIDs are similar for both deterioration and improvement in health status. This study investigates and compares these clinical thresholds for three widely-used questionnaires.Design and settingData were retrospectively analysed from an inhouse 3-week pulmonary rehabilitation (PR) randomised controlled trial in the German Klinik Bad Reichenhall (study 1), and observational research in Dutch primary and secondary routine clinical practice (RCP) (study 2).ParticipantsPatients with COPD aged ≥18 years (study 1) and aged ≥40 years (study 2) without respiratory comorbidities were included for analysis.Primary outcomesThe COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) were completed at baseline and at 3, 6 and 12 months. A Global Rating of Change scale was added at follow-up. Anchor-based and distribution-based methods were used to determine clinically relevant thresholds.ResultsIn total, 451 patients were included from PR and 207 from RCP. MCIDs for deterioration ranged from 1.30 to 4.21 (CAT), from 0.19 to 0.66 (CCQ), and from 2.75 to 7.53 (SGRQ). MCIDs for improvement ranged from −3.78 to −1.53 (CAT), from −0.50 to −0.19 (CCQ), and from −9.20 to −2.76 (SGRQ). Thresholds for moderate improvement versus deterioration ranged from −5.02 to −3.29 vs 3.89 to 8.14 (CAT), from −0.90 to −0.72 vs 0.42 to 1.23 (CCQ), and from −15.85 to −13.63 vs 7.46 to 9.30 (SGRQ).ConclusionsMCID ranges for improvement and deterioration on the CAT, CCQ and SGRQ were somewhat similar. However, estimates for moderate and large change varied and were inconsistent. Thresholds differed between study settings.Trial registration numberRoutine Inspiratory Muscle Training within COPD Rehabilitation trial: #DRKS00004609; MCID study: #UMCG201500447.

Alcohol and cannabis are two of the most commonly used substances by adolescents and are associated with adverse medical and psychiatric outcomes. These adverse psychiatric outcomes may reflect the negative impact of alcohol and/or cannabis abuse on neural systems mediating reward and/or error detection. However, work indicative of this has mostly been conducted in adults with Alcohol and/or Cannabis Use Disorder (i.e., AUD and CUD), with relatively little work in adolescent patients. Furthermore, of the work that has been conducted in adolescents, groups were based on categorical diagnoses of AUD and/or CUD, so the relationship between AUD and/or CUD symptom severity in adolescents and neural dysfunction is unclear. We used a Monetary Incentive Delay (MID) task to examine the relationship between AUDIT and/or CUDIT scores and functional integrity of neuro-circuitries mediating reward processing and error detection within 150 adolescents. Our findings indicate that AUDIT score is negatively related to activity in reward processing neuro-circuitry in adolescents. However, CUDIT score is negatively related to activity in brain regions involved in error detection. Each of these relationships reflected a medium effect size (Partial-η2 0.09-0.14). These data suggest differential impacts of AUD and CUD on reward versus error detection neuro-circuitries within the adolescent brain. Keywords: Adolescent, Alcohol use disorder, Anterior cingulate cortex, Cannabis use disorder, fMRI, Striatum

Despite extensive behavioral evidence of impairments in face processing and expression recognition in adults with alcohol or cannabis use disorders (AUD/CUD), neuroimaging findings have been inconsistent. Moreover, relatively little work has examined the relationship of AUD or CUD symptoms with face or expression processing within adolescents. Given the high prevalence of alcohol and cannabis use during adolescence, understanding how these usage behaviors interact with neural mechanisms supporting face and expression processing could have important implications for youth social and emotional functioning. In this study, adolescents (N = 104) responded to morphed fearful and happy expressions during fMRI and their level of AUD and/or CUD symptoms were related to the BOLD response data. We found that AUD and CUD symptom severity were both negatively related to responses to faces generally. However, whereas this relationship was shown for AUD within ventromedial prefrontal cortex and lingual gyrus, it was shown for CUD within rostromedial prefrontal cortex including anterior cingulate cortex. Additionally, AUD symptom levels were associated with differential responses within medial temporal pole and inferior parietal lobule as a function of expression. These results have potential implications for understanding the social and emotional functioning of adolescents with AUD and CUD symptoms.

Objectives Minimal clinically important differences (MCIDs) are used as fixed numbers in the interpretation of clinical trials. Little is known about its dynamics. This study aims to explore the impact of baseline score, study setting, and patient characteristics on health status MCIDs in chronic obstructive pulmonary disease (COPD). Study Design and Setting Baseline and follow-up data on the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and St. George's Respiratory Questionnaire (SGRQ) were retrospectively analyzed from pulmonary rehabilitation (PR) and routine clinical practice (RCP). Anchor- and distribution-based MCID estimates were calculated and tested between settings, gender, age, Global initiative for Obstructive Lung Disease (GOLD) classification, comorbidities, and baseline health status. Results In total, 658 patients were included with 2,299 change score measurements. MCID estimates for improvement and deterioration ranged for all subgroups 0.50–6.30 (CAT), 0.10–0.84 (CCQ), and 0.33–12.86 (SGRQ). Larger MCID estimates for improvement and smaller ones for deterioration were noted in patients with worse baseline health status, females, elderly, GOLD I/II patients, and patients with less comorbidities. Estimates from PR were larger. Conclusion Baseline health status and setting affected MCID estimates of COPD health status questionnaires. Patterns were observed for gender, age, spirometry classification, and comorbidity levels. These outcomes would advocate the need for tailored MCIDs.

Rosuvastatin is a widely prescribed antihyperlipidemic which undergoes limited metabolism, but is an in vitro substrate of multiple transporters [organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP1A2, OATP2B1, sodium-taurocholate cotransporting polypeptide, breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), MRP4, organic anion transporter 3]. It is therefore frequently used as a probe substrate in clinical drug-drug interaction (DDI) studies to investigate transporter inhibition. Although each of these transporters is believed to play a role in rosuvastatin disposition, multiple pharmacogenetic studies confirm that OATP1B1 and BCRP play an important role in vivo. Ronacaleret, a drug-development candidate for treatment of osteoporosis (now terminated), was shown to inhibit OATP1B1 in vitro (IC50 = 11 µM), whereas it did not inhibit BCRP. Since a DDI risk through inhibition of OATP1B1 could not be discharged, a clinical DDI study was performed with rosuvastatin before initiation of phase II trials. Unexpectedly, coadministration with ronacaleret decreased rosuvastatin exposure by approximately 50%, whereas time of maximal plasma concentration and terminal half-life remained unchanged, suggesting decreased absorption and/or enhanced first-pass elimination of rosuvastatin. Of the potential in vivo rosuvastatin transporter pathways, two might explain the observed results: intestinal OATP2B1 and hepatic MRP4. Further investigations revealed that ronacaleret inhibited OATP2B1 (in vitro IC50 = 12 µM), indicating a DDI risk through inhibition of absorption. Ronacaleret did not inhibit MRP4, discharging the possibility of enhanced first-pass elimination of rosuvastatin (reduced basolateral secretion from hepatocytes into blood). Therefore, a likely mechanism of the observed DDI is inhibition of intestinal OATP2B1, demonstrating the in vivo importance of this transporter in rosuvastatin absorption in humans.

Several malnutrition screening tools have been advocated for use in pediatric inpatients.We evaluated how 3 popular pediatric nutrition screening tools [i.e., the Pediatric Yorkhill Malnutrition Score (PYMS), the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and the Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS)] compared with and were related to anthropometric measures, body composition, and clinical variables in patients who were admitted to tertiary hospitals across Europe.The 3 screening tools were applied in 2567 inpatients at 14 hospitals across 12 European countries. The classification of patients into different nutritional risk groups was compared between tools and related to anthropometric measures and clinical variables [e.g., length of hospital stay (LOS) and infection rates].A similar rate of completion of the screening tools for each tool was achieved (PYMS: 86%; STAMP: 84%; and STRONGKIDS: 81%). Risk classification differed markedly by tool, with an overall agreement of 41% between tools. Children categorized as high risk (PYMS: 25%; STAMP: 23%; and STRONGKIDS: 10%) had a longer LOS than that of children at low risk (1.4, 1.4, and 1.8 d longer, respectively; P < 0.001). In high-risk patients identified with the PYMS, 22% of them had low (

Background The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant. Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID. This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St. George’s Respiratory Questionnaire (SGRQ). Methods Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR). CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months. A 15-point Global Rating of Change scale (GRC) was completed at each follow-up. A five-point GRC was used as second anchor at 12 months. Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID. The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency. Results In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up. Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ). MCID estimates for improvement ranged − 3.1 to − 1.4 for CAT, − 0.6 to − 0.3 for CCQ, and − 10.3 to − 7.6 for SGRQ. Absolute higher – though not significant – MCIDs were observed for CAT and CCQ directly after PR. Significantly absolute lower MCID estimates were observed for CAT (difference − 1.4: CI -2.3 to − 0.5) and CCQ (difference − 0.2: CI -0.3 to −0.1) using a five-point GRC. Conclusions The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values. However, the design of the anchor question was likely to influence the MCID of CAT and CCQ. Trial registration RIMTCORE trial #DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer). Electronic supplementary material The online version of this article (10.1186/s12955-018-0950-7) contains supplementary material, which is available to authorized users.

Previous studies reported a wide range of estimated malnutrition prevalence (6-30%) in paediatric inpatients based on various anthropometric criteria. We performed anthropometry in hospitalised children and assessed the relationship between malnutrition and length of hospital stay (LOS) and complication rates.In a prospective multi-centre European study, 2567 patients aged 1 month to 18 years were assessed in 14 centres in 12 countries by standardised anthropometry within the first 24 h after admission. Body mass index (BMI) and height/length-2 standard deviation scores (SDS, WHO reference) were related to LOS (primary outcome), frequency of gastrointestinal (diarrhoea and vomiting) and infectious complications (antibiotic use), weight change during stay (secondary outcomes) and quality of life.A BMI-2 SDS was present in 7.0% of the patients at hospital admission (range 4.0-9.3% across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1-2 years (8.3%). A BMI-2 to ≥-3 SDS (moderate malnutrition) and a BMI-3 SDS (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95: 1.27, 2.10) days longer LOS, respectively (p = 0.04 and p0.001). Reduced BMI-2 SDS was also associated to lower quality of life, and more frequent occurrence of diarrhoea (22% vs 12%, p0.001) and vomiting (26% vs 14%, p0.001).Disease associated malnutrition in hospitalised children in Europe is common and is associated with significantly prolonged LOS and increased complications, with possible major cost implications, and reduced quality of life. This study was registered at clinicaltrials.gov as NCT01132742.

Objective Oxidative stress has been implicated in pregnancy-induced hypertension and preeclampsia. There is still some debate over whether this is confined to the placenta or occurs in the maternal circulation. This study was designed to investigate this question by comparing parameters of oxidative stress in samples of maternal blood and cord blood taken from normotensive and hypertensive pregnant women. A further aim was to compare these parameters in maternal milk from the two populations. Study design Forty-six hypertensive (31 preeclamptic and 15 chronic hypertensive) and 60 normotensive pregnant women were recruited. Antecubital blood was collected from each woman before and after delivery, cord blood just after delivery, and maternal milk for the first 3 days post-partum. Total antioxidant capacity, total peroxides and sulphydryl concentration were measured and total antiox-idant capacity calculated for each specimen. Results For all specimens (maternal blood plasma, cord blood plasma, maternal milk) total antioxidant capacity and sulphydryl concentration were significantly lower in the hypertensive women than in the normotensive, while total peroxide and oxidative stress index were significantly higher. Conclusion These results support the association between hypertension in pregnancy and oxidative stress and the view that this occurs throughout the maternal circulation. They show further that oxidative stress may be transmitted from mother to newborn in maternal milk. Supplementation with antioxidants could, in view of our findings, possibly provide protection to the mother and fetus and also, through transmission in maternal milk, to the newborn. © 2011 Springer-Verlag.

WOS: 000269782800005, PubMed: 19541303, Objective: To evaluate retrospectively the prevalence of cervical cytological abnormalities in patient records obtained from healthcare centers in Turkey. Method: Demographic characteristics and data on cervical cytological abnormalities were evaluated from patients who underwent flap tests in healthcare centers in 2007. Results: Data were collected from 33 healthcare centers totaling 140 334 patients. Overall, the prevalence of cervical cytological abnormalities was 1.8%; the prevalence of ASCUS, ASC-H, LSIL, HSIL, and AGC was 1.07%, 0.07%, 0.3%, 0.17%, and 0.08%, respectively. The prevalence of preinvasive cervical neoplasia was 1.7% and the prevalence of cytologically diagnosed invasive neoplasia was 0.06%. Conclusion: The abnormal cervical cytological prevalence rate in Turkey is lower than in Europe and North America. This might be due to sociocultural differences, lack of population-based screening programs, or a lower HPV prevalence rate in Turkey. (C) 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ischemia, hypoxia, and elevated vascular resistance disturb placental functions by increasing oxidative stress. Heat shock protein 70 (HSP70) is an oxidative stress marker. Endothelial nitric oxide synthase (eNOS) is a nitric oxide enzyme with a key role in pathologic and physiologic angiogenesis and vasculogenesis. This study was performed to investigate the role of oxidative stress in the pathogenesis of preeclampsia and intrauterine growth-restricted (IUGR) pregnancies by comparing the levels of HSP70 and eNOS in placentas from women with these diseases and those with healthy pregnancies.HSP70 and eNOS were examined using the streptavidin-biotin-peroxidase complex technique on formalin-fixed, paraffin-embedded sections from 135 placental villous tissues obtained from normal pregnancies (n=45) and pregnancies complicated with preeclampsia (n=45) and IUGR (n=45). The intensity of labeling in placental tissues with antibodies to HSP70 and eNOS was scored between 0 and 3, using a semiquantitative scale.HSP70 and eNOS levels were increased in the syncytiotrophoblasts, cytotrophoblasts, and extravillous trophoblast cells of preeclamptic and IUGR placentas (P

Objective: Females with Sjögren's Syndrome (SS) often experience vaginal dryness and dyspareunia, along with glandular and extraglandular symptoms. We aimed to evaluate sexual function and life quality in women with SS. Methods: Forty-six premenopausal women with SS and 47 age-matched controls were studied. Age, duration of the disease, medications, and comorbid diseases were noted. Participants completed 36-Item Short Form Health Survey (SF-36) and Female Sexual Function Index (FSFI). Patients were asked about vaginal discharge and itching in the last month, and if they informed their rheumatologists about any sexual problems. Gynecologic examinations were performed and vaginal smears were taken on each participant. Results: The median total scores of FSFI were significantly lower in the SS group than the controls [17.12 (2.4-27.8) and 27.4 (16.9-36.0), respectively, p < 0.001]. In the SS group, 37 (80.4%) and in the control group 18 (38.3%) of patients were sexually dissatisfied (p < 0.001). Vaginal dryness and lubricant use were significantly increased in patients with SS compared to controls (p < 0.001). Life quality scores were significantly lower in patients with SS than the controls (p < 0.001). Vaginal dryness was negatively correlated with FSFI total (r = −0.312, p = 0.035) and subscores except desire and arousal. Physical functioning, role physical and role emotional scores were positively correlated with total FSFI scores (r = 0.449, p = 0.002, r = 0.371, p = 0.011, r = 0.299, p = 0.043, respectively). Conclusions: Women with SS experience less satisfaction with sexual activity, which can be affected by age, vaginal dryness, physical pain, and impaired function due to the disease. Therefore, rheumatologists should pay attention to these symptoms and management. RESUMO Objetivo: As mulheres com síndrome de Sjögren (SS) muitas vezes experimentam secura vaginal e dispareunia, juntamente com sintomas glandulares e extraglandulares. Este estudo objetivou avaliar a função sexual e a qualidade de vida de mulheres com SS. Métodos: Estudaram-se 46 mulheres pré-menopáusicas com SS e 47 controles pareados por idade. Avaliaram-se a idade, a duração da doença, os medicamentos usados e as comorbidades. As participantes preencheram o questionário de qualidade de vida 36-Item Short Form Health Survey(SF-36) e o Female Sexual Function Index (FSFI). As pacientes foram perguntadas quanto à presença de corrimento e prurido vaginal no último mês e se haviam informado a seus reumatologistas sobre quaisquer problemas sexuais. Fizeram-se exames ginecológicos e esfregaços vaginais de todas as participantes. Resultados: A mediana do escore total do FSFI foi significativamente menor no grupo SS do que no grupo controle [17,12 (2,4 a 27,8) e 27,4 (16,9 a 36), respectivamente, p < 0,001]. Nos grupos SS e controle, 37 (80,4%) e 18 (38,3%) das pacientes estavam sexualmente insatisfeitas, respectivamente (p < 0,001). A presença de secura vaginal e o uso de lubrificantes foram significativamente mais frequentes em pacientes com SS em relação aos controles (p < 0,001). Os índices de qualidade de vida foram significativamente menores nas pacientes com SS do que nos controles (p < 0,001). A secura vaginal esteve negativamente correlacionada com o FSFI total (r = −0,312 p = 0,035) e com todos os seus subescores, exceto desejo e excitação. Os escores de capacidade funcional, aspecto físico e aspecto emocional se correlacionaram positivamente com a pontuação total do FSFI (r = 0,449, p = 0,002; r = 0,371, p = 0,011; r = 0,299, p = 0,043, respectivamente). Conclusões: As mulheres com SS têm menor satisfação com a atividade sexual, o que pode ser afetado pela idade, secura vaginal, dor física e função prejudicada em razão da doença. Portanto, os reumatologista devem prestar atenção a esses sintomas e seu tratamento.

Background/Aim: The purpose of this study was to prove the effect of complete surgical staging of patients with mucinous borderline ovarian tumors (mBOTs) especially appendectomy on progression-free survival (PFS) and overall survival (OS). Patients and Methods: The database of 14 gynecological oncology departments from Turkey and Germany were comprehensively searched forwomen who underwent primary surgery for an ovarian tumor between January 1, 1998, and December 31, 2015, and whose final diagnosis was mBOT. Results: A total of 364 patients with mBOT with a median age of 43.1 years were included in this analysis. The median OS of all patients was 53.1 months. The majority of cases had Stage IA (78.6%). In univariate and multivariate analyses, radical surgery, omentectomy, appendectomy, lymphadenectomy, and adding adjuvant chemotherapy were not independent prognostic factors for PFS and OS. Furthermore, FIGO stage (?IC vs.

Objective: To analyze the expression patterns of extracellular signal-regulated kinase (ERK1/2) and phosphorylated (p)-AKT in the tissues of non-pathologic endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer using indirect immunohistochemistry, and also to investigate the effect of ERK1/2 and p-AKT expression patterns on prognosis in endometrioid adenocancer. Study design: Immunolocalization of ERK1/2 and p-AKT was examined in six different types of endometrial tissues: proliferative endometrium (PE; n = 10, 11.2%), secretuar endometrium (SE; n = 10, 11.2%), simple hyperplasia (SH; n = 15, 16.9%), complex hyperplasia (CH; n = 3, 3.4%) and atypical complex hyperplasia (ACH; n = 10, 11.2%), which were obtained from endometrial biopsies, curettage materials, and hysterectomy specimens and classified as the benign group; and both early stage endometrioid (n = 21, 23.6%) and advanced stage endometrioid adenocancer (AC; n = 20, 22.5%), which were obtained from complete surgical staging materials and classified as the malignant group. All specimens were fixed in 10% formalin and processed using routine paraffin protocols. Immunostaining intensities were evaluated as negative or weak (assigned as low expression) and moderate or strong (assigned as high expression). Results: In the malignant group, 23 of 41 patients (56.1%) had high ERK1/2 and p-AKT expression, whereas only three of 48 patients in the benign group (6.3%) had high ERK1/2 and p-AKT expression (P < 0.0001 and P < 0.0001, respectively). p-AKT expression was significantly higher in women with positive lymph nodes (OR 9.0; 95% CI: 1.2-100.0; P = 0.03). Higher expression of p-AKT was significantly associated with poor progression-free survival (PFS) and overall survival (OS). In contrast, ERK1/2 expression was not associated with PFS or OS.Conclusions ERK1/2 and p-AKT can be useful in the differential diagnosis of benign vs. malignant endometrial lesions, as well as early vs. advanced stage endometrioid endometrial adenocancer. Additionally, higher p-AKT expression could be used as a marker of poor prognosis in the management of patients with endometrioid endometrial adenocancer. © 2014 Elsevier Ireland Ltd. All rights reserved.

Social referencing paradigms in humans and observational learning paradigms in animals suggest that emotional expressions are important for communicating valence. It has been proposed that these expressions initiate stimulus-reinforcement learning. Relatively little is known about the role of emotional expressions in reinforcement learning, particularly in the context of social referencing. In this study, we examined object valence learning in the context of a social referencing paradigm. Participants viewed objects and faces that turned toward the objects and displayed a fearful, happy or neutral reaction to them, while judging the gender of these faces. Notably, amygdala activation was larger when the expressions following an object were less expected. Moreover, when asked, participants were both more likely to want to approach, and showed stronger amygdala responses to, objects associated with happy relative to objects associated with fearful expressions. This suggests that the amygdala plays two roles in social referencing: (i) initiating learning regarding the valence of an object as a function of prediction errors to expressions displayed toward this object and (ii) orchestrating an emotional response to the object when value judgments are being made regarding this object.

The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT). Participants were 145 Dutch children (8-18 years old, M = 12.5 years, 57% girls) with a primary anxiety disorder. Assessments were completed pretreatment, in-treatment, posttreatment, and at 3-month follow-up. Sequential temporal dependencies between putative mediators and parent- and child-reported anxiety symptoms were investigated in AMOS using longitudinal Latent Difference Score Modeling. During treatment an increase of positive thoughts preceded a decrease in child-reported anxiety symptoms. An increase in three coping strategies (direct problem solving, positive cognitive restructuring, and seeking distraction) preceded a decrease in parent-reported anxiety symptoms. A reciprocal effect was found for perceived control: A decrease in parent-reported anxiety symptoms both preceded and followed an increase in perceived control. Using a longitudinal design, a temporal relationship between several putative mediators and CBT-outcome for anxious children was explored. The results suggest that a change in positive thoughts, but not negative thoughts, and several coping strategies precedes a change in symptom reduction and, therefore, at least partly support theoretical models of anxiety upon which the anxiety intervention is based.

The current study examined temporal discounting (the decrease in subjective reward value as a function of increasing delay) in youths with conduct disorder (CD) and the extent to which this was modulated by level of psychopathic traits. In the temporal discounting task, participants were asked to choose between immediate rewards of varying values and a larger reward, held at a constant value ($10), whose receipt was delayed by different time intervals across trials (e.g., 7 days, 360 days). The level of immediate reward necessary for selection over the larger, delayed reward is the measure of temporal discounting. Forty-six youths (21 with CD and 25 healthy youths) participated in this study. Compared with healthy youths, youths with CD chose significantly smaller amounts of immediate reward rather than the larger future rewards. This was the case even in youths with CD without comorbid attention-deficit/hyperactivity disorder. However, level of psychopathic traits did not modulate temporal discounting in this sample. These results are discussed in terms of neurobiological models of CD and psychopathic traits.

This cross-sectional study examines the association of amount and different type of childhood maltreatment with responsiveness in regions of the brain implicated in emotional responding and response control in youths., Key Points Question Are the amount and type (abuse vs neglect) of childhood maltreatment differentially associated with the responsiveness of regions of the brain implicated in emotional responding and response control? Findings In this cross-sectional study including 116 youths aged 10 to 18 years, the amount of childhood maltreatment was inversely associated with the responsiveness of regions of the brain involved in response control and positively associated with emotional responding. This association was also found specifically for abuse but not for neglect. Meaning Different types of childhood maltreatment may have different associations with atypical neural responses; therefore, they may have different associations with different forms of psychiatric neurobiology., Importance Childhood maltreatment is associated with serious developmental consequences that may be different depending on the form of maltreatment. However, relatively little research has investigated this issue despite implications for understanding the development of psychiatric disorders after maltreatment. Objective To determine the association of childhood maltreatment and potential differential associations of childhood abuse or neglect with neural responsiveness within regions of the brain implicated in emotional responding and response control. Design, Setting, and Participants In this cross-sectional study, participants aged 10 to 18 years with varying levels of prior maltreatment as indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from a residential care facility and the surrounding community. Blood oxygen level–dependent response data were analyzed via 2 analyses of covariance that examined 2 (sex) × 3 (task condition [view, congruent, incongruent]) × 3 (valence [negative, neutral, positive]) with Blom-transformed covariates: (1) total CTQ score; and (2) abuse and neglect subscores. Data were collected from April 1, 2016, to June 30, 2018. Data analyses occurred from June 10, 2018, to October 31, 2018. Main Outcomes and Measures Blood oxygenation level–dependent signals in response to an Affective Stroop task were measured via functional magnetic resonance imaging. Results The sample included 116 youths (mean [SD] age, 15.0 [2.2] years; 70 [60.3%] male). Fifteen participants reported no prior maltreatment. The remaining 101 participants (87.1%) reported at least some prior maltreatment, and 55 (54.5%) reported significant maltreatment, ie, total CTQ scores were greater than the validated CTQ score threshold of 40. There were significant total CTQ score × task condition associations within the bilateral postcentral gyrus, left precentral gyrus, midcingulate cortex, middle temporal gyrus, and superior temporal gyrus (left postcentral gyrus: F = 11.73; partial η2 = 0.14; right postcentral and precentral gyrus: F = 9.81; partial η2 = 0.10; midcingulate cortex: F = 12.76; partial η2 = 0.12; middle temporal gyrus: F = 13.24; partial η2 = 0.10; superior temporal gyrus: F = 10.33; partial η2 = 0.11). In all examined regions of the brain, increased maltreatment was associated with decreased differential responsiveness to incongruent task trials compared with view trials (left postcentral gyrus: r = −0.34; 95% CI, −0.17 to −0.51; right postcentral and precentral gyrus: r = −0.31; 95% CI, −0.14 to −0.49; midcingulate cortex: r = −0.36; 95% CI, −0.18 to −0.53; middle temporal gyrus: r = −0.35; 95% CI, −0.17 to −0.52; superior temporal gyrus: r = −0.37; 95% CI, −0.20 to −0.55). These interactions were particularly associated with level of abuse rather than neglect. A second analysis of covariance revealed significant abuse × task condition (but not neglect × task) interactions within the midcingulate cortex (F = 13.96; partial η2 = 0.11), right postcentral gyrus and inferior parietal lobule (F = 15.21; partial η2 = 0.12), left postcentral and precentral gyri (F = 11.16; partial η2 = 0.12), and rostromedial frontal cortex (F = 10.36; partial η2 = 0.08)). In all examined regions of the brain, increased abuse was associated with decreased differential responsiveness to incongruent task trials compared with view trials (midcingulate cortex: partial r = −0.33; P

Background The functional significance of the impairment shown by patients with ADHD on response inhibition tasks is unclear. Dysfunctional behavioral and BOLD responses to rare no-go cues might reflect disruption of response inhibition (mediating withholding the response) or selective attention (identifying the rare cue). However, a factorial go/no-go design (involving high and low frequency go and no-go stimuli) can disentangle these possibilities. Methods Eighty youths [22 female, mean age = 13.70 (SD = 2.21), mean IQ = 104.65 (SD = 13.00); 49 with diagnosed ADHD] completed the factorial go/no-go task while undergoing fMRI. Results There was a significant response type-by-ADHD symptom severity interaction within the left anterior insula cortex; increasing ADHD symptom severity was associated with decreased recruitment of this region to no-go cues irrespective of cue frequency. There was also a significant frequency-by-ADHD symptom severity interaction within the left superior frontal gyrus. ADHD symptom severity showed a quadratic relationship with responsiveness to low frequency cues (irrespective of whether these cues were go or no-go); within this region, at lower levels of symptom severity, increasing severity was associated with increased BOLD responses but at higher levels of symptom severity, decreasing BOLD responses. Conclusion The current study reveals two separable forms of dysfunction that together probably contribute to the impairments shown by patients with ADHD on go/no-go tasks., Highlights • Youths with ADHD show impairment in response inhibition and sustained attention. • A factorial go/no-go task can separate dysfunctions in ADHD. • Response inhibition was associated with decreased anterior insula activation. • Sustained attention was related to decreased superior frontal cortex activation. • There are two separable forms of dysfunctions in ADHD.

Purpose: To determine knowledge levels of working and student nurses about cervical cancer and prophylactic cancer vaccines. Materials and Methods: This study was performed on 259 nursing students in the Department of Nursing and 137 nurses working in Health Research and Practice Center, approved to participate in the study between April-June 2012. The study was performed universally without selecting a sample. A questionnaire that was prepared for evaluating participants’ knowledge and attitudes about human papilloma virus (HPV) vaccine was distributed to the nurses and data obtained from the forms were transferred to SPSS 15.00 program and statistically analyzed. Results: It was found that 54.8% of the student nurses were between 21-24 years old and 13.1% of working students were between 25-28 years old. When student nurses and working nurses were compared in terms of their knowledge about the causes of cervical cancer, their ideas about prevention from cervical cancer with HPV vaccine, their ideas about possible risks of HPV vaccine and conservation ratios of HPV vaccine, it was observed that there were no statistically significant differences (p>0.05). When student nurses and working nurses were compared in terms of the information-source about HPV, ways of HPV contamination, awareness about people who are susceptible to HPV contamination and age of HPV vaccination, it was determined that there was a statistically significant difference (p

The pathologic mechanisms underlying the gestational trophoblastic diseases are largely unexplored, but are thought to involve oxidative damage to the maternal vasculature and also to the placenta. In this study we have assessed the plasma levels of total antioxidant response (TAR) and the levels of endogenous DNA damage--determined by the comet assay--in peripheral blood lymphocytes from 13 women with complete hydatidiform mole (CHM) and compared these with those of 12 healthy pregnant controls and 10 healthy non-pregnant controls. Significantly lower mean levels of plasma TAR were found in patients with CHM compared with healthy pregnant controls (1.08+/-0.29 versus 1.17+/-0.14 mmol Trolox Eq/L, p0.05) and with healthy non-pregnant controls (1.08+/-0.29 versus 1.38+/-0.12 mmol Trolox Eq/L, p0.05). Significantly higher mean levels of endogenous DNA damage were observed in patients with CHM than in healthy pregnant controls (234.5+/-50.74 versus 125.7+/-45.4 AU, p0.05) or in healthy non-pregnant controls (234.5+/-50.74 versus 104.0+/-49.6 AU, p0.05). We observed an inverse correlation between the plasma TAR and the levels of endogenous DNA damage (r=-0.64, p0.01), in that the levels of oxidative damage to the DNA were found to parallel the decrease in the plasma TAR in the CHM group. These results reveal a relationship between the extracellular and intracellular (as reflected by damage to the DNA) levels of oxidation. Our observations suggest that there is a link between the increased levels of oxidative stress and the increase in endogenous DNA damage seen in patients with CHM, as compared with those seen in normal pregnancy. However, the nature of this link, and whether it is direct or indirect, remains to be explored.

Objectives : Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. Study design : Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. Results : Statistically significant differences (determined using Student’s t -test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31±0.12 mmol versus 1.06±0.41 mmol Trolox eq./L; 30.2±17.83 μmol/L versus 18.1±11.37 μmol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8±14.3 μmol/L versus 38.8±9.6 μmol/L). Conclusions : We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia.

Objective To evaluate the effectiveness of sibutramine therapy alone and in combination with ethinyl estradiol-cyproterone acetate (EE-CPA) on the clinical and metabolic parameters of obese women with polycystic ovary syndrome (PCOS). Design Prospective randomized, controlled study. Setting Endocrinology and gynecology clinics. Patient(s) Forty obese women with PCOS. Intervention(s) Group 1 was treated with oral EE-CPA (35 μg-2 mg/day), group 2 with oral sibutramine (10 mg/day), and group 3 with a combination of EE-CPA plus sibutramine for 6 months. All groups were advised to consume a diet of 1,200 kcal/day. Main outcome measure(s) Measurements were performed before and 6 months after treatment of body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, Ferriman-Gallwey hirsutism score, total testosterone, free testosterone, sex hormone–binding globulin, dihydroepiandrosterone sulfate (DHEAS), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose and insulin during oral glucose tolerance test, and insulin sensitivity index; area under the curve for glucose and insulin were obtained from OGTT. Result(s) Body mass index, Ferriman-Gallwey hirsutism score, serum total testosterone, free testosterone, and DHEAS levels were significantly decreased and SHBG was significantly increased in all groups at the end of the study. WHR, diastolic blood pressure, and serum triglyceride level were significantly reduced only in the sibutramine group. Conclusion(s) Sibutramine might have a positive effect on hyperandrogenemia, and clinical and metabolic risk factors for cardiovascular disease in obese women with PCOS.

Background: Cosmetic products contribute considerably to the incidence of contact dermatitis. In response to a resolution of the Council of Europe, the National Institute for Public Health and the Environment (RIVM) in The Netherlands set up a pilot project to report undesirable effects attributed to cosmetic products. Objectives: To provide an overview of undesirable effects attributed to cosmetic products and to identify the ingredients involved. The information could contribute to the assessment of whether current EU legislation on cosmetics provides adequate protection. Patients/methods: General practitioners, dermatologists and consumers in The Netherlands completed questionnaires on reported undesirable effects of cosmetics. Dermatologists also carried out patch tests and, where necessary, tests with specific batch ingredients of the associated cosmetic product. A website and a public awareness campaign were launched to encourage consumers to report undesirable effects. Results: Between July 2009 and May 2011, the RIVM received more than 1600 reports. Severe undesirable effects were claimed in 1–4% of the cases. The most frequently reported cosmetic products were make-up and moisturisers, and the most frequently identified allergens were isothiazolinones and fragrance ingredients. Three patients tested positive for co-polymers/cross-polymers. Conclusions: Further investigations are recommended on the prevalence of isothiazolinone-induced allergic contact dermatitis and the allergenic potential of co-polymers/cross-polymers. (aut. ref.)

Aims and objectives: The Critical Nursing Situation Index (CNSI) is a checklist to detect nursing protocol violations. The objectives of this study were to determine incidences and severities of nursing protocol violations and to check whether corrective actions were taken. Design: Prospective observational audit. Methods: This study was performed in the Intensive Care Unit of the Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. The CNSI was applied in the period February 2009 to February 2010 by 14 purpose-trained nurses whose interrater reliability had proved sufficient. The checklist addressed nine domains of nursing care: Basic care, Circulation, Respiration, Digestive tract, Infection, Invasive catheters, Medication, ECMO and Central nervous system. The trained nurses also recorded whether violations were discussed with the bedside nurse, whether they could be corrected; and whether they were justifiable. Protocol violations are justifiable when protocol adherence carries greater risk of harm to the patient. Results: Protocol violations were identified for 987 of 8107 items (12·2%) checked in 238 observations in 126 patients. The percentage of protocol violations varied from 5% in the Medication domain to 26% in the Digestive tract domain. More than fifty percent (53·4%) of all protocol violations were corrected in the same shift; 22·3% of all protocol violations proved justifiable, however, these were rarely documented (6·4% of cases). Nurses' classification of the severity of the protocol violations was not reliable because linearly weighted kappa varied from 0 to 0·33. Conclusions: The CNSI is a useful tool to monitor and correct nursing protocol violations. Relevance to clinical practice: Timely identification and correction of protocol violations will reduce possible adverse events resulting from these violations. Furthermore, this study made us aware that protocol violations may be justifiable in clinical practice provided they are well documented.

Background & aims: Efforts are directed at reaching the optimal composition of pediatric amino acids (AA) infusions. The goal was to demonstrate the safety and efficacy of a newly developed parenteral AA solution containing alanyl-glutamine (GLN-AA) compared to Standard-AA. Methods: This is a randomized (2:1), double-blind, multicentre clinical pilot trial. Infants after surgical interventions were allocated to receive GLN-AA or Standard-AA over a minimum of 5 days to maximum of 10 days. AA profiles in blood samples obtained at baseline, day 7, and end of treatment were compared to normal ranges. Data regarding safety, and efficacy were also collected. Results: Infants were comparable for (safety population) gestational age at birth (36 vs 38 weeks), birth weight (2460 vs 2955 g), and day of life during start intervention (1 vs 2 days). Plasma AA profiles in infants treated with GLN-AA (n = 13) were closer the normal ranges than those in infants treated with Standard-AA (n = 6). There were no clinical or statistical differences in adverse events, safety and efficacy parameters between both groups. Conclusion: This first-in-man study shows that GLN-AA is safe in infants after surgical interventions, and is well tolerated. Compared to reference values, GLN-AA better reflects the amino acid requirements of the infant.

Individuals with substance abuse (SA) histories show impairment in the computations necessary for decision-making, including expected value (EV) and prediction error (PE). Neuroimaging findings, however, have been inconsistent. Sixteen youth with (SApositive) and 29 youth without (SAnegative) substance abuse histories completed a passive avoidance task while undergoing functional MRI. The groups did not significantly differ on age, gender composition or IQ. Behavioral results indicated that SApositive youth showed significantly less learning than SAnegative youth over the task. SApositive youth show problems representing EV information when attempting to avoid sub-optimal choices in bilateral inferior frontal gyrus and striatum. Furthermore, SApositive youth showed a significantly increased differential response to reward versus punishment feedback modulated by PE in posterior cingulate cortex relative to SAnegative youth. Disrupted decision-making is likely to exacerbate SA as a failure to represent EV during the avoidance of sub-optimal choices is likely to increase the likelihood of SA. With respect to the representation of PE, future work will be needed to clarify the impact of different substances on the neural systems underpinning PE representation. Moreover, interaction of age/development and substance abuse on PE signaling will need to be explored.

The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28–0.61 (CCQ), 1.46–3.08 (CAT) and 6.86–9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.

To evaluate the diagnostic and the predictive value of Arizona Sexual Experience Scale among primary infertile couples regarding sexual dysfunction.The cross-sectional and prospective pre, post study comprising primary infertile patients was carried out at Bulent Ecevit University Hospital, Zonguldak, Turkey. Fifty consecutive primary infertile couples not treated previously were investigated between 2003 and 2007 for the presence of sexual dysfunction by a psychiatrist. Arizona Sexual Experience Scale scoring was self-administered to determine sexual dysfunction among couples before treatment and also 3 months after the initiation of the treatment.Pretreatment mean values of the index parametres in both women and men were significantly increased after treatment. Statistically significant positive correlation was observed between pre- and post-treatment total scores in both women (r = 0.83; p.001) and men (r = 0.92; p.001). Receiver operating characteristic curve analyses revealed optimum cut-offs of pre- and post-treatment scores in women were were14 (Sensitivity: 57%; Specificity: 90%) and13 (Sensitivity: 83%; Specificity: 93%), respectively. Pre- and post-treatment scores in men were10 (Sensitivity: 65%; Specificity: 61%),11 (Sensitivity: 83%; Specificity: 62%), respectively. Binary logistic regression analyses revealed women's pre-treatment and post-treatment scores as a significant factor for prediction of sexual dysfunction independent of sociodemographic factors (p = 0.001 and p = 0.001, respectively).Evaluation and treatment of infertility is an important risk factor for sexual dyfunction. Pre- and posttreatment Arizona Sexual Experience Scale score could be used as a screening test for sexual dysfunction and might be used to decide pre/post-treatment consultation of couples with a specialist.

Background: In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ >= 1, CAT >= 10, and mMRC scale >= 2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George's Respiratory Questionnaire (SGRQ) >= 25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (>= 25 and >= 20). Materials and methods: Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. Results: Sensitivity, specificity, and AUC scores for cutoff point SGRQ >= 25 were: study A, 0.99, 0.43, and 0.96 for CCQ >= 1, 0.92, 0.48, and 0.89 for CAT >= 10, and 0.68, 0.91, and 0.91 for mMRC >2; study B, 0.87, 0.77, and 0.9 for CCQ >1, 0.76, 0.73, and 0.82 for CAT >10, and 0.21, 1, and 0.81 for mMRC >= 2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ >= 20 were: study A, 0.99, 0.73, and 0.99 for CCQ >= 1, 0.91, 0.73, and 0.94 for CAT >= 10, and 0.66, 0.95, and 0.94 for mMRC >= 2; study B, 0.8, 0.89, and 0.89 for CCQ >= 1, 0.69, 0.78, and 0.8 for CAT >= 10, and 0.18, 1, and 0.81 for mMRC >= 2. Conclusion: Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (>25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory, though not optimal. The SGRQ threshold of >= 20 corresponded slightly better than SGRQ >= 25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale.