Reduced neural sensitivity to social stimuli in infants at risk for autism

In the hope of discovering early markers of autism, attention has recently turned to the study of infants at risk owing to being the younger siblings of children with autism. Because the condition is highly heritable, later-born siblings of diagnosed children are at substantially higher risk for developing autism or the broader autism phenotype than the general population. Currently, there are no strong predictors of autism in early infancy and diagnosis is not reliable until around 3 years of age. Because indicators of brain functioning may be sensitive predictors, and atypical social interactions are characteristic of the syndrome, we examined whether temporal lobe specialization for processing visual and auditory social stimuli during infancy differs in infants at risk. In a functional near-infrared spectroscopy study, infants aged 4–6 months at risk for autism showed less selective neural responses to social stimuli (auditory and visual) than low-risk controls. These group differences could not be attributed to overall levels of attention, developmental stage or chronological age. Our results provide the first demonstration of specific differences in localizable brain function within the first 6 months of life in a group of infants at risk for autism. Further, these differences closely resemble known patterns of neural atypicality in children and adults with autism. Future work will determine whether these differences in infant neural responses to social stimuli predict either later autism or the broader autism phenotype frequently seen in unaffected family members

CKS1 expression in melanocytic nevi and melanoma

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway. © Brozyna et al

The health profile of people living with Parkinson\u27s Disease managed in a comprehensive care setting

Background: Globally there are few reports of the impairments, disabilities and medications used in people living with idiopathic Parkinson’s disease. Caregiver characteristics and caregiver burden have seldom been reported. We examined the health status in a large cohort of people living with Parkinson’s disease and their caregivers managed in a comprehensive health care setting. Methods/Design: A prospective, cross sectional analysis of impairments, disabilities and Parkinson’s disease medication use was conducted in a sample of 100 people with Parkinson’s disease rated I-IV on the modified Hoehn & Yahr scale. Participants were recruited from the Victorian Comprehensive Parkinson Program in Melbourne, Australia. Their caregivers were invited to provide their views on the burden of care, services provided and support received. Results: The severity of impairments and disabilities was strongly associated with disease duration (mean of 5.5 years). Those with long standing disease or more severe disease also used more Parkinson’s disease medications and participated in fewer social roles than people who were newly diagnosed or mildly affected. The severity of impairments was strongly correlated with limitations in performing activities of daily living. Limitations in performing daily activities were also found to be a significant contributing factor for health-related quality of life (PDQ-39 SI β=0.55, p=0.000; EQ-5D SI β=0.43, p=0.001). People with Parkinson’s disease lived at home with relatives. The average caregiver was a spouse or child providing approximately 3.5 hours of care per day, with the capacity to provide 9.4 hours per day and had provided care for four years. Additional support was high (63%) for 2.5 hours per day. Conclusion: The comprehensive care setting of this cohort describes a relatively benign condition despite a wide range of disease duration and severity. This report provides a baseline with which to compare other delivery models

Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease

Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD) (n = 210) were randomized into three groups: (1) progressive strength training (PST); (2) movement strategy training (MST); or (3) control (“life skills”). PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80%) did not differ between groups (P = .435). Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice

Using exomarkers to assess mitochondrial reactive species in vivo

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium catio

Microwave observations of spinning dust emission in NGC6946

We report new cm-wave measurements at five frequencies between 15 and 18GHz of the continuum emission from the reportedly anomalous "region 4" of the nearby galaxy NGC6946. We find that the emission in this frequency range is significantly in excess of that measured at 8.5GHz, but has a spectrum from 15-18GHz consistent with optically thin free-free emission from a compact HII region. In combination with previously published data we fit four emission models containing different continuum components using the Bayesian spectrum analysis package radiospec. These fits show that, in combination with data at other frequencies, a model with a spinning dust component is slightly preferred to those that possess better-established emission mechanisms.Comment: submitted MNRA

Cost of living with Parkinson\u27s disease over 12 months in Australia: a prospective cohort study

Background. Parkinson disease (PD) is a costly chronic condition in terms of managing both motor and nonmotor symptoms. The burden of disease is high for individuals, caregivers, and the health system. The aim of this study is to estimate the annual cost of PD from the household, health system, and societal perspectives. Methods. A prospective cohort study of newly referred people with PD to a specialist PD clinic in Melbourne, Australia. Participants completed baseline and monthly health resource use questionnaires and Medicare data were collected over 12 months. Results. 87 patients completed the 12-month follow-up assessments. The mean annual cost per person to the health care system was $32,556 AUD. The burden to society was an additional$45,000 per annum per person with PD. The largest component of health system costs were for hospitalisation (69% of total costs). The costs for people with moderate to severe disease were almost 4 times those with mild PD ($63,569 versus$17,537 p < 0.001 ). Conclusion. PD is associated with significant costs to individuals and to society. Costs escalated with disease severity suggesting that the burden to society is likely to grow with the increasing disease prevalence that is associated with population ageing