The putative role of viruses, bacteria, and chronic fungal biotoxin exposure in the genesis of intractable fatigue accompanied by cognitive and physical disability

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Assumptions of decision-making capacity: the role supporter attitudes play in the realisation of Article 12 for people with severe or profound intellectual disability

The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) was the first legally binding instrument explicitly focused on how human rights apply to people with disability. Amongst their obligations, consistent with the social model of disability, the Convention requires signatory nations to recognise that “…persons with disabilities enjoy legal capacity on an equal basis with others in all aspects of life” and mandates signatory nations to develop “…appropriate measures to provide access by persons with disability to the support they may require in exercising their legal capacity”. The Convention promotes supported decision-making as one such measure. Although Australia ratified the UNCRPD in 2008, it retains an interpretative declaration in relation to Article 12 (2, 3, 4), allowing for the use of substituted decision-making in situations where a person is assessed as having no or limited decision-making capacity. Such an outcome is common for people with severe or profound intellectual disability because the assessments they are subjected to are focused on their cognition and generally fail to take into account the interdependent nature of human decision-making. This paper argues that Australia’s interpretative declaration is not in the spirit of the Convention nor the social model of disability on which it is based. It starts from the premise that the intention of Article 12 is to be inclusive of all signatory nations’ citizens, including those with severe or profound cognitive disability. From this premise, arises a practical need to understand how supported decision-making can be used with this group. Drawing from evidence from an empirical study with five people with severe or profound intellectual disability, this paper provides a rare glimpse on what supported decision-making can look like for people with severe or profound intellectual disability. Additionally, it describes the importance of supporters having positive assumptions of decision-making capacity as a factor affecting supported decision-making. This commentary aims to give a focus for practice and policy efforts for ensuring people with severe or profound cognitive disability receive appropriate support in decision-making, a clear obligation of signatory nations of the UNCRPD. A focus on changing supporter attitudes rather than placing the onus of change on people with disability is consistent with the social model of disability, a key driver of the UNCRPD.

Autonomia do indivíduo com deficiência: estudo de caso no transtorno invasivo do desenvolvimento

A presente dissertação viu no estudo do conceito da autonomia o caminho para valorizar a liberdade de decisão do deficiente cognitivo, especificamente o portador de transtorno invasivo do desenvolvimento, ou autista. Como base teórica, foi utilizada a Bioética, pelo seu papel de mediadora entre as ciências médicas e a filosofia. Primeiramente, realizou-se um relato histórico do conceito de autonomia e a contextualização da sua relação com a Bioética. Como o conceito filosófico de pessoa nem sempre é atribuído ao autista, entender a razão dessa distinção é complementar a compreensão do porque não ser atribuída autonomia para esses indivíduos. Os portadores de deficiências vivem uma situação especial de vulnerabilidade, portanto, o conceito de vulnerabilidade e sua relação com a deficiência também fazem parte do estudo. Para uma melhor compreensão de quem é o autista realizou-se uma breve revisão bibliográfica sobre o autismo, priorizando as informações atuais. Somou-se ao levantamento teórico um estudo de caso, onde foi acompanhado um portador adulto da patologia. Com isso, esperava-se avaliar de maneira qualitativa a autonomia do indivíduo. Ter autonomia é fundamental para garantir uma boa qualidade de vida, por isso a Bioética sugere sua proteção e ampliação. Discutir como isso será realizado é fundamental para evitar as formas de paternalismo que reduzem a pessoalidade. Explorar o conceito de autonomia não visa limitar e sim ampliar as possibilidades para todo e qualquer ser-humano. A presente dissertação viu no estudo do conceito da autonomia o caminho para valorizar a liberdade de decisão do deficiente cognitivo, especificamente o portador de transtorno invasivo do desenvolvimento, ou autista. Como base teórica, foi utilizada a Bioética, pelo seu papel de mediadora entre as ciências médicas e a filosofia. Primeiramente, realizou-se um relato histórico do conceito de autonomia e a contextualização da sua relação com a Bioética. Como o conceito filosófico de pessoa nem sempre é atribuído ao autista, entender a razão dessa distinção é complementar a compreensão do porque não ser atribuída autonomia para esses indivíduos. Os portadores de deficiências vivem uma situação especial de vulnerabilidade, portanto, o conceito de vulnerabilidade e sua relação com a deficiência também fazem parte do estudo. Para uma melhor compreensão de quem é o autista realizou-se uma breve revisão bibliográfica sobre o autismo, priorizando as informações atuais. Somou-se ao levantamento teórico um estudo de caso, onde foi acompanhado um portador adulto da patologia. Com isso, esperava-se avaliar de maneira qualitativa a autonomia do indivíduo. Ter autonomia é fundamental para garantir uma boa qualidade de vida, por isso a Bioética sugere sua proteção e ampliação. Discutir como isso será realizado é fundamental para evitar as formas de paternalismo que reduzem a pessoalidade. Explorar o conceito de autonomia não visa limitar e sim ampliar as possibilidades para todo e qualquer ser-humano.

Hezkuntza sistemaren erantzuna autismoa duen ikasleriari eskola inklusiboaren ikuspuntutik

PDFs sin acceso a petición de la autora

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

Factores que detienen la generación de unidades de la meta en empresas que prestan servicios de rehabilitación a personas en condición de discapacidad

El objetivo del presente trabajo es el de presentar los diferentes factores administrativos que determinan la velocidad de generación de unidades de la meta de empresas que prestan servicios de rehabilitación a personas en condición de discapacidad física y/o cognitiva del Distrito Capital. Para cumplir este objetivo nos centramos en el estudio de una Institución tipo que presta servicios de rehabilitación, especialmente a niños con discapacidad. El alcance del trabajo, es la caracterización de una empresa que brinda servicios de rehabilitación, revisar que factores administrativos pueden resaltarse como importantes y necesarios dentro de la organización, establecer cuales son los efectos indeseables que tiene una institución de este tipo y por ultimo estimar cual puede ser el factor restrictivo que detiene la velocidad de generación de las unidades de meta de este tipo de empresas. Los autores aplicaron la Teoría de Restricciones TOC en este trabajo, por considerar que desde su filosofía, esta teoría proporciona los lineamientos para aproximarse a la problemática y para sugerir soluciones, que están plasmadas en un plan de acción de inmediata implementación y con rápidos y eficaces resultados. Esperamos que con este estudio se contribuya en la reflexión y en la redefinición de las empresas que prestan servicios de rehabilitación, para lograr, con las herramientas que la Teoría de Restricciones brinda, el desarrollo de un pensamiento interno que favorezca la mejora continua la cual redundara en mejores servicios para sus usuarios.

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

Proposta de Intervenção para Auxiliar a Reabilitação Motora e Cognitiva de Pacientes com Acidente Vascular Cerebral

Stroke is the leading cause of combined motor and cognitive disability worldwide. The rehabilitation of stroke patients is mostly directed towards motor recovery through the training of the affected member under supervision of a Physical Therapist. In the present study we introduce a new approach for both cognitive and motor therapy, which relies on motor imagery of the upper limbs and working memory training. This therapy should be utilized as an adjuvant to physical therapy. Ten individuals (5 men and 5 women) were selected for the pilot study, all of them in the acute phase of the first ischemic stroke episode. The control group had 5 individuals who were submitted to physical therapy only, whilst the other 5 patients in the experimental group also performed the cognitive and motor training with a video game specially built for this study. Two patients left the experimental group before the end. Total training lasted for 9 weeks, 2 times a week, for half an hour. Patients reported they enjoyed playing the game, even though it required a lot of mental effort, according to them. Plus, they considered it had a beneficial influence in their activities of daily living. No side effects were reported. Preliminary results suggest there is a difference between groups in cognitive and upper limb motor evaluation following the intervention. It is important to notice that our conclusions are limited due the small sample number. Overall, this work is supported by other studies in literature focused in rehabilitation with motor imagery and working memory and indicate a continuity of the research, increasing total training hours

Prevalência de incontinência urinária e fatores associados em idosos institucionalizados

Urinary incontinence (UI) is a geriatric syndrome that is especially prevalent in institutionalized individuals, and that causes economic and social impacts derived from treatment costs and overload of caregiver. UI also entails physical consequences to the health of the elderly, such as urinary tract infections or pressure ulcers, among other health problems. However, the existing national research on this condition is still scarce and comprises serious methodological biases. Therefore, the objective of this study is to determine the prevalence of urinary incontinence and associated factors in institutionalized elderly. A cross-sectional study is presented herein, conducted between October and December, 2013 and carried out in 10 nursing homes in the city of Natal (Northeast Brazil). UI was verified through the program Minimum Data Set version 3.0, which was also used to assess fecal incontinence, urinary devices and UI control programs. Data collection included sociodemographic information, UI characterization, as well as variables related to the institution itself and to health conditions (comorbidities, medication, pelvic floor surgery, Barthel Index for functional capacity and Pfeiffer test for cognitive status). Bivariate analysis was performed using the Chi-Square Test (or Fisher‟s Exact Test) and the Linear Chi-Square Test, calculating the prevalence ratio with 95% confidence interval. Variables with p value under 0.20 were included in the multivariate analysis, which was performed using the Stepwise Forward logistic regression. The inclusion of variables in the final model depended on the likelihood ratio test, absence of multicollinearity and on the Hosmer-Lemeshow test. A statistical significance level of 0.05 was considered. Six (1.8%) hospitalized elderly, one individual in palliative care (0.3%) and one (0.3%) individual under the age of 60 were excluded from the study. The final sample consisted of 321 elderly, mostly females, with a mean age of 81.5 years. The prevalence of UI was 59.43% and the final model revealed statistically a significant association between UI and white race, physical inactivity, stroke, mobility constraints and cognitive decline. The most frequent UI type was functional UI due to physical or cognitive disability, and incontinence control measures were applied only to a minority of residents (approximately 8%). It is concluded that UI is a health issue that affects more than half of the institutionalized elderly, and is associated with white race, physical inactivity, stroke and other geriatric syndromes such as immobility and cognitive disability. Most of these associated factors are modifiable and therefore the findings of this study highlight the importance of UI prevention and treatment in nursing homes, which include general measures, such as physical and psychosocial activities, and specific measures, such as prompted voiding

Longevity and stroke: a study on 1.176 GeHA 90+ Italian sibs

Preface: The improvements of the social-environmental conditions, and medical cares and the quality of life caused a general improvement of the health status of the population, with a consequent reduction of the overall morbidity and mortality, resulting in an increase of life expectancy that has rose dramatically in the last century. Stroke represents the 3rd cause of death and 1st cause of disability in Europe and in Italy. Aim: The aim of this research is to explore the prevalence of stroke in 1.176 90+ Italian sibs, collected from the north, centre and south of the peninsula, and examine the presence of functional and cognitive disability in the stroke affected sibs. Materials and Methods: We divided our sample in three main categories a)Stroke free(960 subjects, 88.72%), b)Young age stroke, reported age of Stroke incidence < 85 y.o.(42 subjects, 3.88%), c)Old age stroke, reported age of Stroke incidence ≥ 85y.o.(80 subjects, 7.39%). We examine cognitive impairment using the MMSE and functional disability using the ADL scale, the chair stand and hand-grip test. The three groups for each test have been analysed according the following parameters: age at interview, sex, ability to understand the questions, can the participant walk 500 m without help, smoke habit, alcohol daily consumption, presence of serious memory impairments (e.g. dementia), Daily Exercise or daily light housework, History of arthritis. Results: After performing mulrivariate analysis, amazingly the young ictus group had worst performance in all the cognitive and functional variables.

Effect of loss of CDKL5 on brain development in a new Cdkl5 knockout mouse model

Rett's Syndrome (RTT) is a severe neurodevelopmental disorder, characterized by cognitive disability that appears in the first months/years of life. Recently, mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been detected in RTT patients characterized by early-onset seizures. CDKL5 is highly expressed in the brain starting from early postnatal stages to adulthood, suggesting the importance of this kinase for proper brain maturation and function. However, the role/s of CDKL5 in brain development and the molecular mechanisms whereby CDKL5 exerts its effects are still largely unknown. In order to characterize the role of CDKL5 on brain development, we created a mice carrying a targeted conditional knockout allele of Cdkl5. A first behavioral characterization shows that Cdkl5 knockout mice recapitulate several features that mimic the clinical features described in CDKL5 patients and are a useful tool to investigate phenotypic and functional aspects of Cdkl5 loss. We used the Cdkl5 knockout mouse model to dissect the role of CDKL5 on hippocampal development and to establish the mechanism/s underlying its actions. We found that Cdkl5 knockout mice showed increased precursor cell proliferation in the hippocampal dentate gyrus. Interestingly, this region was also characterized by an increased rate of apoptotic cell death that caused a reduction in the final neuron number in spite of the proliferation increase. Moreover, loss of Cdkl5 led to decreased dendritic development of new generated granule cells. Finally, we identified the Akt/GSK3-beta signaling as a target of Cdkl5 in the regulation of neuronal precursor proliferation, survival and maturation. Overall our findings highlight a critical role of CDKL5/AKT/GSK3-beta signaling in the control of neuron proliferation, survival and differentiation and suggest that CDKL5-related alterations of these processes during brain development underlie the neurological symptoms of the CDKL5 variant of RTT.

Pharmacological Rescue of Dendritic Pathology in the Ts65Dn Mouse Model of Down Syndrome

Down syndrome (DS) is a genetic pathology characterized by brain hypotrophy and severe cognitive disability. Although defective neurogenesis is an important determinant of cognitive impairment, a severe dendritic pathology appears to be an equally important factor. It is well established that serotonin plays a pivotal role both on neurogenesis and dendritic maturation. Since the serotonergic system is profoundly altered in the DS brain, we wondered whether defects in the hippocampal development can be rescued by treatment with fluoxetine, a selective serotonin reuptake inhibitor and a widely used antidepressant drug. A previous study of our group showed that fluoxetine fully restores neurogenesis in the Ts65Dn mouse model of DS and that this effect is accompanied by a recovery of memory functions. The goal of the current study was to establish whether fluoxetine also restores dendritic development and maturation. In mice aged 45 days, treated with fluoxetine in the postnatal period P3-P15, we examined the dendritic arbor of newborn and mature granule cells of the dentate gyrus (DG). The granule cells of trisomic mice had a severely hypotrophic dendritic arbor, fewer spines and a reduced innervation than euploid mice. Treatment with fluoxetine fully restored all these defects. Moreover the impairment of excitatory and inhibitory inputs to CA3 pyramidal neurons was fully normalized in treated trisomic mice, indicating that fluoxetine can rescue functional connectivity between the DG and CA3. The widespread beneficial effects of fluoxetine on the hippocampal formation suggest that early treatment with fluoxetine can be a suitable therapy, possibly usable in humans, to restore the physiology of the hippocampal networks and, hence, memory functions. These findings may open the way for future clinical trials in children and adolescents with DS.

A study of nurses' judgement of and participation in decision-making for nursing home placement for the elderly

This study investigated the effects of patient variables (physical and cognitive disability, significant others' preference and social support) on nurses' nursing home placement decision-making and explored nurses' participation in the decision-making process.^ The study was conducted in a hospital in Texas. A sample of registered nurses on units that refer patients for nursing home placement were asked to review a series of vignettes describing elderly patients that differed in terms of the study variables and indicate the extent to which they agreed with nursing home placement on a five-point Likert scale. The vignettes were judged to have good content validity by a group of five colleagues (expert consultants) and test-retest reliability based on the Pearson correlation coefficient was satisfactory (average of.75) across all vignettes.^ The study tested the following hypotheses: Nurses have more of a propensity to recommend placement when (1) patients have severe physical disabilities; (2) patients have severe cognitive disabilities; (3) it is the significant others' preference; and (4) patients have no social support nor alternative services. Other hypotheses were that (5) a nurse's characteristics and extent of participation will not have a significant effect on their placement decision; and (6) a patient's social support is the most important, single factor, and the combination of factors of severe physical and cognitive disability, significant others' preference, and no social support nor alternative services will be the most important set of predictors of a nurse's placement decision.^ Analysis of Variance (ANOVA) was used to analyze the relationships implied in the hypothesis. A series of one-way ANOVA (bivariate analyses) of the main effects supported hypotheses one-five.^ Overall, the n-way ANOVA (multivariate analyses) of the main effects confirmed that social support was the most important single factor controlling for other variables. The 4-way interaction model confirmed that the most predictive combination of patient characteristics were severe physical and cognitive disability, no social support and the significant others did not desire placement. These analyses provided an understanding of the importance of the influence of specific patient variables on nurses' recommendations regarding placement. ^

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Del pictograma a la imagen: herramientas de comunicación y lenguaje en personas con síndrome de Asperger a través de recursos visuales para la inclusión social

Se presenta en este texto, una introducción al Síndrome de Asperger y aquellas características que lo distinguen, con el fin de conocer un poco más, en qué consiste este Trastorno Generalizado del Desarrollo (TGD). Además, se pretende facilitar cuales son las herramientas de comunicación y lenguaje más aptas para la enseñanza y aprendizaje del sujeto, haciendo hincapié en los recursos visuales, audiovisuales y artísticos como herramientas de aprendizaje para su inclusión social en cualquier ámbito de la sociedad (colegios, institutos, asociaciones, universidades o administraciones).