Conservation of the oligomeric state of native VDAC1 in detergent micelles.

The voltage-dependent anion-selective channel (VDAC) is an intrinsic β-barrel membrane protein located within the mitochondrial outer membrane where it serves as a pore, connecting the mitochondria to the cytosol. The high-resolution structures of both the human and murine VDACs have been resolved by X-ray diffraction and nuclear magnetic resonance spectroscopy (NMR) in 2008. However, the structural data are not completely in line with the findings that were obtained after decades of research on biochemical and functional analysis of VDAC. This discrepancy may be related to the fact that structural biology studies of membrane proteins reveal specific static conformations that may not necessarily represent the physiological state. For example, overexpression of membrane proteins in bacterial inclusion bodies or simply the extraction from the native lipid environment using harsh purification methods (i.e. chaotropic agents) can disturb the physiological conformations and the supramolecular assemblies. To address these potential issues, we have developed a method, allowing rapid one step purification of endogenous VDAC expressed in the native mitochondrial membrane without overexpression of recombinant protein or usage of harsh chaotropic extraction procedures. Using the Saccharomyces cerevisiae isoform 1 of VDAC as a model, this method yields efficient purification, preserving VDAC in a more physiological, native state following extraction from mitochondria. Single particle analysis using transmission electron microscopy (TEM) demonstrated conservation of oligomeric assembly after purification. Maintenance of the native state was evaluated using functional assessment that involves an ATP-binding assay by micro-scale thermophoresis (MST). Using this approach, we were able to determine for the first time the apparent KD for ATP of 1.2 mM.

Illusions in advanced cancer: The effect of belief systems and attitudes on quality of life

Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment. In order to evaluate an illusory domain in the context of advanced cancer, we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer, and how committed they were to using alternative treatments. A measure of quality of life was used as the dependent variable in order to assess the association between these attributes. After a preliminary exploration confirmed the presence of an illusory domain, these concepts were prospectively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment, radiation treatment or supportive care. The scale of global quality of life was reliable (Cronbach's alpha coefficient 0.72). The distribution of the scores of will to live was skewed, with no respondent scoring poorly, and the scale was reliable (Cronbach's alpha coefficient 0.82). The scale of belief in curability showed diverse beliefs. In some cases, there was a discrepancy between respondents' beliefs in curability and what they believed to be the report by their doctors. There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer (p

Use of anti-pronation taping to assess suitability of orthotic prescription: Case report

This case report describes a strategy for assessing the suitability of orthotic prescription for individual patients with lower limb overuse injuries. The case concerns a 32 year old male soccer player with a two-year history of Achilles tendinopathy. A functional assessment performed before, during, and after a trial period of anti-pronation taping showed that taping reduced symptoms markedly and resulted in a 10-fold increase in pain-free jogging distance. This was interpreted as an indication for favourable orthotic intervention. Subsequently, orthotic intervention was associated with a similar reduction in symptoms and improvement in function. This case study illustrates how a trial period of anti-pronation taping could assist therapists to make decisions about prescription of orthoses for lower limb overuse injuries.

The impact of rehabilitation support services on health-related quality of life for women with breast cancer

As the number of women surviving breast cancer increases, with implications for the health system, research into the physical and psychosocial sequelae of the cancer and its treatment is a priority. This research estimated self-reported health-related quality of life (HRQoL) associated with two rehabilitation interventions for breast cancer survivors, compared to a non-intervention group. Women were selected if they received an early home-based physiotherapy intervention (DAART, n = 36) or a group-based exercise and psychosocial intervention (STRETCH, n = 31). Questionnaires on HRQoL, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity module, were administered at pre-, post-intervention, 6- and 12-months post-diagnosis. Data on a non-intervention group (n = 208) were available 6- and 12-months post-diagnosis. Comparing pre/post-intervention measures, benefits were evident for functional well-being, including reductions in arm morbidity and upper-body disability for participants completing the DAART service at one-to-two months following diagnosis. In contrast, minimal changes were observed between pre/post-intervention measures for the STRETCH group at approximately 4-months post-diagnosis. Overall, mean HRQoL scores (adjusted for age, chemotherapy, hormone therapy, high blood pressure and occupation type) improved gradually across all groups from 6- to 12-months post-diagnosis, and no prominent differences were found. However, this obscured declining HRQoL scores for 20-40% of women at 12 months post-diagnosis, despite receiving supportive care services. Greater awareness and screening for adjustment problems among breast cancer survivors is required throughout the disease trajectory. Early physiotherapy after surgery has the potential for short-term functional, physical and overall HRQoL benefits.

Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer

Purpose To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue. Patients and Methods This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy-Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value. Results Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy-Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life. Conclusion Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.

A cost-effectiveness analysis of two rehabilitation support services for women with breast cancer

The purpose of this research was to estimate the cost-effectiveness of two rehabilitation interventions for breast cancer survivors, each compared to a population-based, non-intervention group (n = 208). The two services included an early home-based physiotherapy intervention (DAART, n = 36) and a group-based exercise and psychosocial intervention (STRETCH, n = 31). A societal perspective was taken and costs were included as those incurred by the health care system, the survivors and community. Health outcomes included: (a) 'rehabilitated cases' based on changes in health-related quality of life between 6 and 12 months post-diagnosis, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity (FACT-B+4) questionnaire, and (b) quality-adjusted life years (QALYs) using utility scores from the Subjective Health Estimation (SHE) scale. Data were collected using self-reported questionnaires, medical records and program budgets. A Monte-Carlo modelling approach was used to test for uncertainty in cost and outcome estimates. The proportion of rehabilitated cases was similar across the three groups. From a societal perspective compared with the non-intervention group, the DAART intervention appeared to be the most efficient option with an incremental cost of $1344 per QALY gained, whereas the incremental cost per QALY gained from the STRETCH program was $14,478. Both DAART and STRETCH are low-cost, low-technological health promoting programs representing excellent public health investments.

Measuring mobility in frail older people: reliability and validity of the Physical Mobility Scale

Objectives: The study was designed to show the validity and reliability of scoring the Physical Mobility Scale (PMS). PMS was developed by physiotherapists working in residential aged care to specifically show resident functional mobility and to provide information regarding each resident's need for supervision or assistance from one or two staff members and equipment during position changes, transfers, mobilising and personal care. Methods: Nineteen physiotherapists of varying backgrounds and experience scored the performances of nine residents of care facilities from video recordings. The performances were compared to scores on two 'gold standard' assessment tools. Four of the physiotherapists repeated the evaluations. Results: The PAIS showed excellent content validity and reliability. Conclusions: The PAIS provides graded performance of physical mobility, including level of dependency on staff and equipment. This is a major advantage over existing functional assessment tools. There is no need for specific training for physiotherapists to use the tool.

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

Primary objective: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. Research design: A retrospective case note review assessed total rehabilitation unit admission. Methods and procedures: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. Main outcomes and results: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = −6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36–68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002–0.35). Conclusions: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort.

Think Before You Speak: Increasing a Student’s Appropriate Verbal Responses During Classroom Instruction

This study compared the effects of two intervention packages on increasing the appropriate verbal responses of a 7th-grade student. The interventions were determined by the results of a functional assessment of behavior. An alternating interventions design was used. Both intervention packages were successful in increasing the target behavior.

Tradução e adaptação transcultural do domínio função física do Patient-Reported Outcomes Measurement Information System – PROMIS® - versão para a língua portuguesa

In 2004, the National Institutes of Health made available the Patient-Reported Outcomes Measurement Information System – PROMIS®, which is constituted of innovative item banks for health assessment. It is based on classical, reliable Patient-Reported Outcomes (PROs) and includes advanced statistical methods, such as Item Response Theory and Computerized Adaptive Test. One of PROMIS® Domain Frameworks is the Physical Function, whose item bank need to be translated and culturally adapted so it can be used in Portuguese speaking countries. This work aimed to translate and culturally adapt the PROMIS® Physical Function item bank into Portuguese. FACIT (Functional Assessment of Chronic Illness Therapy) translation methodology, which is constituted of eight stages for translation and cultural adaptation, was used. Fifty subjects above the age of 18 years participated in the pre-test (seventh stage). The questionnaire was answered by the participants (self-reported questionnaires) by using think aloud protocol, and cognitive and retrospective interviews. In FACIT methodology, adaptations can be done since the beginning of the translation and cultural adaption process, ensuring semantic, conceptual, cultural, and operational equivalences of the Physical Function Domain. During the pre-test, 24% of the subjects had difficulties understanding the items, 22% of the subjects suggested changes to improve understanding. The terms and concepts of the items were totally understood (100%) in 87% of the items. Only four items had less than 80% of understanding; for this reason, it was necessary to chance them so they could have correspondence with the original item and be understood by the subjects, after retesting. The process of translation and cultural adaptation of the PROMIS® Physical Function item bank into Portuguese was successful. This version of the assessment tool must have its psychometric properties validated before being made available for clinical use.

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study

BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P).

PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study.

RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004).

CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

Instrumentos de Avaliação Psicológica em Idosos

O envelhecimento constitui-se como um fenómeno recente e universal nos países desenvolvidos. Assistimos simultaneamente ao aumento da prevalência de doenças crónicas, pelo que, é premente realizarem-se avaliações geriátricas eficazes, apostando-se em diagnósticos precoces e completos. Deste modo, na presente tese iremos debruçar-nos sobre a avaliação psicológica de adultos, com particular incidência na população idosa, apresentando alguns dos instrumentos mais utilizados para proceder a uma plena avaliação funcional, com enfoque nas pessoas com mais de 65 anos. / Aging constitutes a recent and universal phenomenon in the developed countries Simultaneously, we bear witness of the increase in the prevalence of chronic diseases being thus urgent to carry out effective geriatric assessments, focussing on early and comprehensive diagnoses. Thus, in this dissertation we shall address the adults' psychological evaluation with particular emphasis on the elderly population, presenting some of the most used instruments/tools to make a full functional assessment, with special focus on people over 65 years.

O uso da imagiologia por termografia na medicina dentária

Introdução: No domínio científico da medicina dentária, a termografia é um dos temas mais recentes e que tem levado á publicação de alguns estudos. A combinação da avaliação funcional, características de fluxo sanguíneo e localização anatómica levou a um aumento de aplicações da termografia no diagnóstico clínico. Objetivo: Este trabalho teve como objetivo uma analise bibliografia existente sobre a termografia e as suas aplicações em medicina e medicina dentária, avaliar a sua utilidade no diagnóstico de patologias da área de atuação médico-dentária. Metodologia: Procedeu-se a uma pesquisa bibliográfica através da identificação de artigos publicados em bases de dados eletrónicas internacionais, PubMed, B-on e Science Direct utilizando palavras-chave e critérios de exclusão e inclusão, que permitiram fazer uma seleção prévia dos artigos a incluir ao longo deste trabalho. Resultados: Após a realização da pesquisa bibliográfica obtiveram-se 30 artigos. A partir da amostra encontrada foram excluídos 93 artigos devido à falta de correspondência do seu conteúdo ao tema proposto. Conclusão: Os resultados sugerem que a termografia é uma técnica de imagem que deteta a distribuição do calor da superfície corporal. A termografia Capta e transforma a radiação infravermelha emitida pela pele humana em imagens que refletem a dinâmica da microcirculação cutânea. A termografia é considerada como um técnica não invasiva, indolor, não ionizante, fornecendo informações quantitativas que permitem que seja uma técnica válida para o diagnóstico clinico complementar.

Essays on the Effects of Social Insurance for Disability

This dissertation examines how social insurance, family support and work capacity enhance individuals' economic well-being following significant health and income shocks. I first examine the extent to which the liquidity-enhancing effects of Worker's Compensation (WC) benefits outweigh the moral hazard costs. Analyzing administrative data from Oregon, I estimate a hazard model exploiting variation in the timing and size of a retroactive lump-sum WC payment to decompose the elasticity of claim duration with respect to benefits into the elasticity with respect to an increase in cash on hand, and a decrease in the opportunity cost of missing work. I find that the liquidity effect accounts for 60 to 65 percent of the increase in claim duration among lower-wage workers, but less than half of the increase for higher earners. Using the framework from Chetty (2008), I conclude that the insurance value of WC exceeds the distortionary cost, and increasing the benefit level could increase social welfare. Next, I investigate how government-provided disability insurance (DI) interacts with private transfers to disabled individuals from their grown children. Using the Health and Retirement Study, I estimate a fixed effects, difference in differences regression to compare transfers between DI recipients and two control groups: rejected applicants and a reweighted sample of disabled non-applicants. I find that DI reduces the probability of receiving a transfer by no more than 3 percentage points, or 10 percent. Additional analysis reveals that DI could increase the probability of receiving a transfer in cases where children had limited prior information about the disability, suggesting that DI could send a welfare-improving information signal. Finally, Zachary Morris and I examine how a functional assessment could complement medical evaluations in determining eligibility for disability benefits and in targeting return to work interventions. We analyze claimants' self-reported functional capacity in a survey of current DI beneficiaries to estimate the share of disability claimants able to do work-related activity. We estimate that 13 percent of current DI beneficiaries are capable of work-related activity. Furthermore, other characteristics of these higher-functioning beneficiaries are positively correlated with employment, making them an appropriate target for return to work interventions.