Cortical and motor responses to acute forced exercise in Parkinson's disease

IntroductionStudies in animal models of Parkinson's disease (PD) have suggested that the rate of exercise performance is important in treatment efficacy and neuroprotection. In humans with PD, lower-extremity forced-exercise (FE) produced global improvements in motor symptoms based on clinical ratings and biomechanical measures of upper extremity function.MethodsfMRI was used to compare the underlying changes in brain activity in PD patients following the administration of anti-parkinsonian medication and following a session of FE.ResultsNine individuals with PD completed fMRI scans under each condition: off anti-PD medication, on anti-PD medication, and off medication + FE. Unified Parkinson's Disease Rating Motor Scale scores improved by 50% in the FE condition compared to the off-medication condition. The pattern of fMRI activation after FE was similar to that seen with anti-PD medication. Direct comparison of the fMRI activation patterns showed high correlation between FE and anti-PD medication.ConclusionThese findings suggest that medication and FE likely utilize the same pathways to produce symptomatic relief in individuals with PD.     

Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy

BackgroundPremenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5–10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy.MethodsPOSITIVE enrolled women with stage I-III HR + early breast cancer, ≤42 years, who had received 18–30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration.FindingsFrom 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen + ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had node-negative disease (76.2%) and received tamoxifen + OFS (56.0 %). More European women had received chemotherapy (69.3 %).InterpretationThe characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world.     

Age-related decline of gait variability in children with attention-deficit/hyperactivity disorder: Support for the maturational delay hypothesis in gait

BackgroundPrevious findings showed a tendency toward higher gait variability in children with attention-deficit/hyperactivity disorder (ADHD) compared to controls. This study examined whether gait variability in children with ADHD eventually approaches normality with increasing age (delay hypothesis) or whether these gait alterations represent a persistent deviation from typical development (deviation hypothesis).MethodThis cross-sectional study compared 30 children with ADHD (25 boys; M_age = 10 years 11 months, range 8–13 years; n = 21 off medication, n = 9 without medication) to 28 controls (25 boys; M_age = 10 years 10 months, range 8–13 years). Gait parameters (i.e. velocity and variability in stride length and stride time) were assessed using an electronic walkway system (GAITRite) while children walked at their own pace.ResultsChildren with ADHD walked with significantly higher variability in stride time compared to controls. Age was negatively associated with gait variability in children with ADHD such that children with higher age walked with lower variability, whereas in controls there was no such association.ConclusionsChildren with ADHD displayed a less regular gait pattern than controls, indicated by their higher variability in stride time. The age-dependent decrease of gait variability in children with ADHD showed that gait performance became more regular with age and converged toward that of typically developing children. These results may reflect a maturational delay rather than a persistent deviation of gait regularity among children with ADHD compared to typically developing children.     

MIC and other NKG2D ligands: from none to too many

NKG2D, a prime activatory receptor on human NK, CD8(+) alphabeta and gammadelta cells, has a variety of ligands, which, despite sharing membership of the MHC class I structural club, display an array of unique features. Chronologically, human MIC molecules were the first NKG2D ligands to be identified. Then came RAET1 (ULBP) molecules, which were identified in both man and mouse, as well as H60 and MULT1, which have no counterparts in man to date. The question remains as to why, more than how, the evolutionary conserved, apparently monomorphic, single copy, NKG2D, can/should adapt to this variety of ligands, and when it does, what is the evolutionary advantage of this profusion of ligands for a single receptor?     

Acute stepwise challenge test with levodopa in treated patients with parkinsonism

ObjectiveThe aim of this study was to establish a new stepwise type of acute challenge test with incremental doses of levodopa/benserazide, and verify its predictive value in follow-up diagnoses and outcomes of deep-brain stimulation (DBS) in treated patients with parkinsonism.DesignProspective cohort study.OutcomesThe optimal cutoff points for UPDRS-III improvement in these stepwise levodopa tests. In this study, we established acute challenge tests with incremental doses of levodopa/benserazide (100/25 mg, 150/37.5 mg, 200/50 mg and 300/75 mg) in treated patients with parkinsonism (n = 175). The receiver operating characteristic (ROC) curves were plotted to compare peak UPDRS-III improvement of PD patients (n = 112) with that of non-PD parkinsonism patients (n = 63). The point on the ROC curve with the highest Youden index was defined as the optimal cutoff point in motor improvement for differential diagnoses. The results of the new tests were compared with follow-up diagnoses and the outcomes of DBS.ResultsThe optimal cutoff points for UPDRS-III improvement with maximal Youden Indices on ROC curves from the tests, with the four incremental doses of levodopa/benserazide, were 12.2% (100/25 mg), 22.3% (150/37.5 mg), 27.9% (200/50 mg) and 33.4% (300/75 mg). The test showed significant correlation with follow-up diagnosis and the outcomes of DBS (P of Kappa <0.01).ConclusionsThe results suggested that the new acute stepwise levodopa challenge test is a useful tool for the diagnosis of PD.     

Emotional and behavioral problems in preschool children with autism: Relationship with sensory processing dysfunction

This study aimed to investigate the sensory processing (SP) dysfunction and emotional and behavioral problems in preschool children with autism and then examine the relationship between the SP dysfunction and emotional and behavioral problems. The parents of 112 children aged 48–84 months (67 with autism; 45 age-matched typically developing) completed a demographic questionnaire, the Child Behavior Checklist-Chinese version (CBCL-C), and the Sensory Profile-Chinese version (SP-C). We found that 95.8% of children with autism who showed significant internalizing problems had at least one SP quadrant in the definite difference range, while 81.8% with significant externalizing problems had at least one SP quadrant in the definite difference range. Typically developing children showed lower percentages of 66.7% and 40.0%. Stepwise linear regression analysis revealed that in children with autism, avoiding and male gender were significant predictors of internalizing problems and sensitivity was a significant predictor of externalizing problems. In contrast, in typically developing children, avoiding was a significant predictor of internalizing problems and seeking was a significant predictor of externalizing problems. This study provided further understanding of the factors influencing emotional and behavioral problems in autism.