Beyond individual differences: are working memory and inhibition informative specifiers within ASD?

Findings on working memory (WM) and inhibition in children with autism spectrum disorders (ASD) are contradictory and earlier studies largely ignored individual differences. As WM and inhibition seem to be related, children who experience WM deficits might also experience inhibition deficits. Moreover, these children possibly form a distinct subgroup, differing on other variables, such as cognitive functioning, symptom severity, behavior, and attention deficit hyperactivity disorder (ADHD) characteristics. We studied a large sample of children with and without ASD (8–12 years, IQ > 80) with classic experimental tasks (n-back task, ASD n = 77, control n = 45; stop task, ASD n = 74, control n = 43), and explored individual differences. The ASD group made more errors on the n-back task with increasing WM load, and had longer stop signal reaction times on the stop task when compared with controls. However, only 6 % of the ASD group showed both WM and inhibition deficits, and 71 % showed no deficits. Parents of children with WM and/or inhibition deficits tended to report more conduct problems on the disruptive behavior disorder rating scale. ADHD characteristics did not influence performance. Some children used medication during testing, which seemingly influenced stop task performance, but excluding these data did not change the main findings. Large individual differences in cognitive functioning are present, even within children with ASD with average or above average intelligence. However, whether individual differences in specific cognitive domains, such as WM and inhibition are as informative as individual differences in diagnosis, comorbidity, and general cognitive functioning, calls for future research.     

Dyspareunia and pelvic floor muscle function before and during pregnancy and after childbirth

Introduction and hypothesis

There is limited knowledge on dyspareunia during pregnancy and postpartum and the role of the pelvic floor muscles (PFM) in women with dyspareunia. Aims of the study were to investigate the presence of dyspareunia before and during pregnancy and postpartum, and to compare vaginal resting pressure (VRP), PFM strength, and endurance between women with and those without dyspareunia. It was hypothesized that there is no difference in PFM variables between women with and those without dyspareunia.

Methods

Three hundred nulliparous women participated in this prospective cohort and answered questions about dyspareunia and the level of bother at gestational weeks 22 and 37, 6 and 12 months postpartum, and retrospectively prior to their pregnancies using ICIQ-FLUTSsex. PFM variables were assessed by manometer at gestational week 22, and 6 and 12 months postpartum. Comparisons between groups were analyzed using independent samples t test.

Results

Twenty-eight and 30 % of the women reported dyspareunia at pre-pregnancy and at gestational week 22 respectively. At gestational week 37, and 6 and 12 months postpartum, the percentages were 40, 45, and 33 respectively. No difference in PFM variables was found between women with and those without dyspareunia. Level of bother was higher postpartum than before and during pregnancy.

Conclusions

Symptoms of dyspareunia were common at all time points. No link could be made between PFM function and dyspareunia. Women suffering from dyspareunia postpartum reported it as being bothersome. Our findings suggest that women should be asked about symptoms of dyspareunia related to pregnancy, and that future research should aim for preventative and therapeutic strategies.     

Long-Term Improvements in Pulmonary Function 5 Years After Bariatric Surgery

Background

Obesity is associated with reduced pulmonary function. We evaluated pulmonary function and status of asthma and obstructive sleep apnoea syndrome (OSAS) before and 5 years after bariatric surgery.

Methods

Spirometry was performed at baseline and 5 years postoperatively. Information of asthma and OSAS were recorded. Of 113 patients included, 101 had undergone gastric bypass, 10 duodenal switch and 2 sleeve gastrectomy.

Results

Eighty (71 %) patients were women, mean preoperative age was 40 years and preoperative weight was 133 kg in women and 158 kg in men. Five years postoperatively, weight reduction was 31 % (42 kg; p?<?0.001) in women and 24 % (38 kg; p?<?0.001) in men. Forced expiratory volume in 1 s (FEV1) increased 4.1 % (116 ml; p?<?0.001) in women and 6.7 % (238 ml; p?=?0.003) in men. Forced vital capacity (FVC) increased 5.8 % (209 ml; p?<?0.001) in women and 7.6 % (349 ml; p?<?0.001) in men. Gender and weight loss were independently associated with the improvements in FEV1 and FVC. At follow-up, FEV1 had increased 36 % of the difference towards the estimated normal FEV1, and there was a corresponding 70 % recovery of FVC. These improvements occurred despite an expected decline in pulmonary function by age during the study period. Of the asthmatics and OSAS patients, 48 and 80 %, respectively, were without symptoms 5 years postoperatively.

Conclusions

Pulmonary function measured with spirometry was significantly improved 5 years after bariatric surgery, despite an expected age-related decline during this period. Symptoms of asthma and OSAS also improved.     

Clinical Validation of the Cervista HPV HR Test According to the International Guidelines for Human Papillomavirus Test Requirements for Cervical Cancer Screening

This study demonstrates that both the clinical sensitivity and specificity of the Cervista HPV HR test for high-risk human papillomavirus (HPV) detection are not inferior to those of the Hybrid Capture 2 (HC2) test. The intra- and interlaboratory reproducibilities of Cervista were 92.0% (kappa, 0.83) and 90.4% (kappa, 0.80), respectively. The Cervista HPV HR test fulfills all the international HPV test requirements for cervical primary screening purposes.     

Profiles of orofacial dysfunction in different diagnostic groups using the Nordic Orofacial Test (NOT-S)—A review

Objective. The Nordic Orofacial Test-Screening (NOT-S) was developed as a comprehensive method to assess orofacial function. Results from the screening protocol have been presented in 11 international publications to date. This study reviewed these publications in order to compile NOT-S screening data and create profiles of orofacial dysfunction that characterize various age groups and disorders. Materials and methods. NOT-S results of nine reports meeting the inclusion criteria were reviewed. Seven of these studies not only provided data on the mean and range of total NOT-S scores, but also on the most common domains of orofacial dysfunction (highest rate of individuals with dysfunction scores), allowing the construction of orofacial dysfunction profiles based on the prevalence of dysfunction in each domain of NOT-S. Results. The compiled data comprised 669 individuals, which included healthy control subjects (n = 333) and various patient groups (n = 336). All studies reported differences between individuals with diagnosed disorders and healthy control subjects. The NOT-S data could measure treatment effects and provided dysfunction profiles characterizing the patterns of orofacial dysfunction in various diagnoses. Conclusions. This review corroborates previous results that the NOT-S differentiates well between patients and healthy controls and can also show changes in individuals after treatment. NOT-S could be used as a standard instrument to assess orofacial dysfunction, evaluate the outcomes of oral habilitation and rehabilitation and improve comparability in clinical practice and research.     

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case–control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0–3.2; p_trend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1–3.9; p_trend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p′-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p′-DDE do not support an association.     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.     

A national study on conditional survival,excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non‐Hodgkin lymphoma

This national population‐based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high‐dose therapy with autologous stem‐cell transplantation (HDT‐ASCT) for non‐Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT‐ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5‐, 10‐ and 20‐year overall survival was 61% (95% confidence interval [CI] 56–64%), 52% (95%CI 48–56%) and 45% (95%CI 40–50%), respectively. The 5‐year survival conditional on having survived 2, 5 and 10 years after HDT‐ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0–13·9), 4·9 (95%CI 4·1–5·9), 2·4 (95%CI 1·8–3·2) and 1·0 (95%CI 0·6–1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT‐ASCT respectively. Of the 281 deaths observed, 77% were relapse‐related. Treatment‐related mortality was 3·6%. The 10‐year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5–2·6). NHL patients treated with HDT‐ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population.