Does cueing training improve physical activity in patients with Parkinson's disease?

Patients with Parkinson’s disease (PD) are encouraged to stay active to maintain their mobility. Ambulatory activity monitoring (AM) provides an objective way to determine type and amount of gait-related daily activities. Objective To investigate the effects of a home cueing training program on functional walking activity in PD. Methods In a single-blind, randomized crossover trial, PD patients allocated to early intervention received cueing training for 3 weeks, whereas the late intervention group received training in the following 3 weeks. Training was applied at home, using a prototype cueing device. AM was applied at baseline, 3, 6, and 12 weeks in the patient’s home, to record body movements. Postures and motions were classified as percentage of total time spent on (a) static activity, further specified as % sitting and % standing, and (b) % dynamic activity, further specified as % walking, % walking periods exceeding 5 seconds (W>5s) and 10 seconds (W>10s). Random coefficient analysis was applied. Results A total of 153 patients participated in this trial. Significant improvements were found for dynamic activity ( = 4.46; P 5s ( = 2.63; P 10s ( = 2.90; P < .01). All intervention effects declined significantly at 6 weeks follow-up. Conclusion Cueing training in PD patients’ own home significantly improves the amount of walking as recorded by AM. Treatment effects reduced after the intervention period, pointing to the need for permanent cueing devices and follow-up cueing training

Validity and reliability of the Dutch translation of the VISA-P questionnaire for patellar tendinopathy

Background: The VISA-P questionnaire evaluates severity of symptoms, knee function and ability to play sports in athletes with patellar tendinopathy. This English-language self-administered brief patient outcome score was developed in Australia to monitor rehabilitation and to evaluate outcome of clinical studies. Aim of this study was to translate the questionnaire into Dutch and to study the reliability and validity of the Dutch version of the VISA-P. Methods: The questionnaire was translated into Dutch according to internationally recommended guidelines. Test-retest reliability was determined in 99 students with a time interval of 2.5 weeks. To determine discriminative validity of the Dutch VISA-P, 18 healthy students, 15 competitive volleyball players (at-risk population), 14 patients with patellar tendinopathy, 6 patients who had surgery for patellar tendinopathy, 17 patients with knee injuries other than patellar tendinopathy, and 9 patients with symptoms unrelated to their knees completed the Dutch VISA-P. Results: The Dutch VISA-P questionnaire showed satisfactory test-retest reliability (ICC = 0.74). The mean (+/- SD) VISA-P scores were 95 (+/- 9) for the healthy students, 89 (+/- 11) for the volleyball players, 58 (+/- 19) for patients with patellar tendinopathy, and 56 (+/- 21) for athletes who had surgery for patellar tendinopathy. Patients with other knee injuries or symptoms unrelated to the knee scored 62 (+/- 24) and 77 (+/- 24). Conclusion: The translated Dutch version of the VISA-P questionnaire is equivalent to its original version, has satisfactory test-retest reliability and is a valid score to evaluate symptoms, knee function and ability to play sports of Dutch athletes with patellar tendinopathy

Prepubertal unilateral gynecomastia: a report of two cases

Item does not contain fulltextBACKGROUND: Gynecomastia is defined as the presence of excessive breast tissue in males, which can appear unilateral or bilateral. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. METHODS: We report the cases of two otherwise healthy boys of 8 and 11 years old with unilateral breast masses. No abnormalities were found on ultrasonography and all endocrine parameters were within normal limits. Treatment consisted of peripheral liposuction followed by subcutaneous partial resection of the gland, conducted through an infra-areolar incision. Results : Microscopy of the subcutaneous mastectomy specimen revealed gynecomastia without signs of malignancy. Postoperative course of both patients was uncomplicated, with no signs of recurrence of breast tissue. CONCLUSIONS: Atypical presentations of gynecomastia are often not recognized, with little attention to breast development in prepubertal non-obese children. Since prepubertal gynecomastia could be a sign of possible underlying diseases, a thorough examination and further research is recommended. If there is no causal treatment, surgical resection is the therapy of first choice. Peripheral liposuction and surgical resection of the gland tissue are the mainstay of treatment. In summary, we describe two cases of prepubertal unilateral gynecomastia with a normal endocrine workup. Further research is needed to establish the pathophysiologic mechanisms of prepubertal gynecomastia, since underlying etiology in most cases remains unclear

Symmetrical Corticobasal Syndrome Caused by a Novel c.314dup Progranulin Mutation

Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer’s disease, Creutzfeldt–Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history

The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial

BACKGROUND: Patellar tendinopathy is a major problem for many athletes, especially those involved in jumping activities. Despite its frequency and negative impact on athletic careers, no evidence-based guidelines for management of this overuse injury exist. Since functional outcomes of conservative and surgical treatments remain suboptimal, new diagnostic and therapeutic strategies have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment in patients with chronic patellar tendinopathy. ESWT is most often applied after the known conservative treatments have failed. However, its effectiveness as primary therapy has not been studied in athletes who keep playing sports despite having patellar tendon pain. The aim of this study is to determine the effectiveness of ESWT in athletes with patellar tendinopathy who are still in training and competition. METHODS/DESIGN: The TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a multicentre two-armed randomised controlled trial with blinded participants and outcome assessors, in which the effectiveness of patient-guided focussed ESWT treatment (compared to placebo ESWT) on pain reduction and recovery of function in athletes with patellar tendinopathy will be investigated. Participants are volleyball, handball and basketball players with symptoms of patellar tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still able to train and compete. The intervention group receives three patient-guided focussed medium-energy density ESWT treatments without local anaesthesia at a weekly interval in the first half of the competition. The control group receives placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after the final ESWT or placebo treatment, when athletes are still in competition. Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment - patella) score. Data with regard to pain during function tests (jump tests and single-leg decline squat) and ultrasound characteristics are also collected. During the follow-up period participants also register pain, symptoms, sports participation, side effects of treatment and additional medical consumption in an internet-based diary. DISCUSSION: The TOPGAME-study is the first RCT to study the effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who are still in training and competition. TRIAL REGISTRATION: Trial registration number NTR1408

A novel microglial subset plays a key role in myelinogenesis in developing brain

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c(+) microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c(+) microglia leads to impairment of primary myelination. CD11c-targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c(+) microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis

Pharmacological characterisation of murine α4β1δ GABAA receptors expressed in Xenopus oocytes

BACKGROUND: GABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence on extrasynaptic GABAA receptor function is less well understood. Here, we examine the pharmacological properties of a potentially native extrasynaptic GABAA receptor that incorporates the β1 subunit, specifically composed of α4β1δ and α4β1 subunits. RESULTS: GABA activated concentration-dependent responses at α4β1δ and α4β1 receptors with EC50 values in the nanomolar to micromolar range, respectively. The divalent cations Zn(2+) and Cu(2+), and the β1-selective inhibitor salicylidine salicylhydrazide (SCS), inhibited GABA-activated currents at α4β1δ receptors. Surprisingly the α4β1 receptor demonstrated biphasic sensitivity to Zn(2+) inhibition that may reflect variable subunit stoichiometries with differing sensitivity to Zn(2+). The neurosteroid tetrahydro-deoxycorticosterone (THDOC) significantly increased GABA-initiated responses in concentrations above 30 nM for α4β1δ receptors. CONCLUSIONS: With this study we report the first pharmacological characterisation of various GABAA receptor ligands acting at murine α4β1δ GABAA receptors, thereby improving our understanding of the molecular pharmacology of this receptor isoform. This study highlights some notable differences in the pharmacology of murine and human α4β1δ receptors. We consider the likelihood that the α4β1δ receptor may play a role as an extrasynaptic GABAA receptor in the nervous system

Air Pollution, Urgent Asthma Medical Visits and the Modifying Effect of Neighborhood Asthma Prevalence

Background: Social and environmental stressors, may modify associations between environmental pollutants and asthma symptoms. We examined if neighborhood asthma prevalence (higher: HAPN vs. lower: LAPN), a surrogate for underlying risk factors for asthma, modified the relationship between pollutants and urgent asthma visits. Methods: Through zip code, home addresses were linked to New York City Community Air Survey’s land use regression model for street-level, annual average nitrogen dioxide (NO2), particulate matter (PM2.5), elemental carbon (EC); summer average ozone (O3); winter average sulfur dioxide (SO2) concentrations. Poisson regression models were fit to estimate the association (prevalence ratio, PR) between pollutant exposures and seeking urgent asthma care. Results: All pollutants, except O3 were higher in HAPN than LAPN (P0.05). Conclusions: Relationships between modeled street-level pollutants and urgent asthma were stronger in LAPN compared to HAPN. Social stressors that may be more prevalent in HAPN than LAPN, could play a greater role in asthma exacerbations in HAPN versus pollutant exposure alone