Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

An approach to the control of disease transmission in pig-to-human xenotransplantation.

Abstract: Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Comparison of phase structures and surface free energy values for the coatings synthesised from linear polyurethanes and from waterborne polyurethane cationomers

WAXS, DSC and AFM methods were employed to compare phase structures of the coatings obtained from waterborne polyurethane cationomers which had been synthesised in the reaction of some diisocyanates (MDI, IPDI, TDI and HDI) with polyoxyethylene glycols (M = 600 and 2,000) and butane1,4-diol or N-methyl- or N-butyldiethanolamine and 2,2,3,3-tetrafluoro-1,4-butanediol. The structures were also analysed of the coatings derived from linear polyurethanes which had been synthesised on the basis of similar raw materials. Better rigidity was found for generally amorphous cationomer coats. Changes were discussed in the surface free energy (SFE) values and in their components, as calculated independently with the use of the van Oss–Good and Owens–Wendt methods. Polyurethane coats turned out more hydrophobic as compared to cationomer ones. In both coat types, fluorine incorporated into cationomers contributed to lower SFE values: from 50 down to about 30 mJ/m2

Barriers to colorectal cancer screening in community health centers: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer screening rates are low among disadvantaged patients; few studies have explored barriers to screening in community health centers. The purpose of this study was to describe barriers to/facilitators of colorectal cancer screening among diverse patients served by community health centers.</p> <p>Methods</p> <p>We identified twenty-three outpatients who were eligible for colorectal cancer screening and their 10 primary care physicians. Using in-depth semi-structured interviews, we asked patients to describe factors influencing their screening decisions. For each unscreened patient, we asked his or her physician to describe barriers to screening. We conducted patient interviews in English (n = 8), Spanish (n = 2), Portuguese (n = 5), Portuguese Creole (n = 1), and Haitian Creole (n = 7). We audiotaped and transcribed the interviews, and then identified major themes in the interviews.</p> <p>Results</p> <p>Four themes emerged: 1) Unscreened patients cited lack of trust in doctors as a barrier to screening whereas few physicians identified this barrier; 2) Unscreened patients identified lack of symptoms as the reason they had not been screened; 3) A doctor's recommendation, or lack thereof, significantly influenced patients' decisions to be screened; 4) Patients, but not their physicians, cited fatalistic views about cancer as a barrier. Conversely, physicians identified competing priorities, such as psychosocial stressors or comorbid medical illness, as barriers to screening. In this culturally diverse group of patients seen at community health centers, similar barriers to screening were reported by patients of different backgrounds, but physicians perceived other factors as more important.</p> <p>Conclusion</p> <p>Further study of these barriers is warranted.</p

Costs of treating patients with schizophrenia who have illness-related crisis events

<p>Abstract</p> <p>Background</p> <p>Relatively little is known about the relationship between psychosocial crises and treatment costs for persons with schizophrenia. This naturalistic prospective study assessed the association of recent crises with mental health treatment costs among persons receiving treatment for schizophrenia.</p> <p>Methods</p> <p>Data were drawn from a large multi-site, non-interventional study of schizophrenia patients in the United States, conducted between 1997 and 2003. Participants were treated at mental health treatment systems, including the Department of Veterans Affairs (VA) hospitals, community mental health centers, community and state hospitals, and university health care service systems. Total costs over a 1-year period for mental health services and component costs (psychiatric hospitalizations, antipsychotic medications, other psychotropic medications, day treatment, emergency psychiatric services, psychosocial/rehabilitation group therapy, individual therapy, medication management, and case management) were calculated for 1557 patients with complete medical information. Direct mental health treatment costs for patients who had experienced 1 or more of 5 recent crisis events were compared to propensity-matched samples of persons who had not experienced a crisis event. The 5 non-mutually exclusive crisis event subgroups were: suicide attempt in the past 4 weeks (n = 18), psychiatric hospitalization in the past 6 months (n = 240), arrest in the past 6 months (n = 56), violent behaviors in the past 4 weeks (n = 62), and diagnosis of a co-occurring substance use disorder (n = 413).</p> <p>Results</p> <p>Across all 5 categories of crisis events, patients who had a recent crisis had higher average annual mental health treatment costs than patients in propensity-score matched comparison samples. Average annual mental health treatment costs were significantly higher for persons who attempted suicide ($46,024), followed by persons with psychiatric hospitalization in the past 6 months ($37,329), persons with prior arrests ($31,081), and persons with violent behaviors ($18,778). Total cost was not significantly higher for those with co-occurring substance use disorder ($19,034).</p> <p>Conclusion</p> <p>Recent crises, particularly suicide attempts, psychiatric hospitalizations, and criminal arrests, are predictive of higher mental health treatment costs in schizophrenia patients.</p