Accelerometric assessment of different dimensions of natural walking during the first year after stroke

Objectives: To describe the course of walking behaviour over a period of 1 year after stroke, using accelerometry, and to compare 1-year data with those from a healthy group. Design: One-year follow-up cohort study. Subjects: Twenty-three stroke patients and 20 age-matched healthy subjects. Methods: Accelerometer assessments were made in the participants' daily environment for 8 h/day during the 1st (T1), 12th (T2) and 48th (T3) weeks after stroke, and at one timepoint in healthy subjects. Primary outcomes were: percentage of time walking and upright (amount); mean duration and number of walking periods (distribution); step regularity and gait symmetry (quality); and walking speed. Results: Time walking, time upright, and number of walking bouts increased during T1 and T2 (p 0.30). Mean duration of walking periods showed no significant improvements (p > 0.30) during all phases. Step regularity, gait symmetry and gait speed showed a tendency to increase consistently from T1 to T3. At T3, amount and distribution variables reached the level of the healthy group, but significant differences remained (p < 0.02) in step regularity and gait speed. Conclusion: In this cohort, different outcomes of walking behaviour showed different patterns and levels of recovery, which supports the multi-dimensional character of gait

To Breve fra Niels Krog Bredal.

The present work has been done within the IAEA Environmental Modelling for Radiation Safety Programme. EMRAS-II aims to improve the capabilities in the field of environmental radiation dose assessment by means of acquisition of improved data for model testing, comparison, reaching consensus on modelling philosophies, approaches and parameter values, development of improved methods and exchange of information

Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication

Background: In all living organisms, DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially disastrous consequences for cell viability and human health, including cancer. To cope with these threats, cells tightly control replication initiation using well-known mechanisms. They also couple DNA synthesis to nutrient richness and growth rate through a poorly understood process thought to involve central carbon metabolism. One such process may involve the cross-species conserved pyruvate kinase (PykA) which catalyzes the last reaction of glycolysis. Here we have investigated the role of PykA in regulating DNA replication in the model system Bacillus subtilis. Results: On analysing mutants of the catalytic (Cat) and C-terminal (PEPut) domains of B. subtilis PykA we found replication phenotypes in conditions where PykA is dispensable for growth. These phenotypes are independent from the effect of mutations on PykA catalytic activity and are not associated with significant changes in the metabolome. PEPut operates as a nutrient-dependent inhibitor of initiation while Cat acts as a stimulator of replication fork speed. Disruption of either PEPut or Cat replication function dramatically impacted the cell cycle and replication timing even in cells fully proficient in known replication control functions. In vitro, PykA modulates activities of enzymes essential for replication initiation and elongation via functional interactions. Additional experiments showed that PEPut regulates PykA activity and that Cat and PEPut determinants important for PykA catalytic activity regulation are also important for PykA-driven replication functions. Conclusions: We infer from our findings that PykA typifies a new family of cross-species replication control regulators that drive the metabolic control of replication through a mechanism involving regulatory determinants of PykA catalytic activity. As disruption of PykA replication functions causes dramatic replication defects, we suggest that dysfunctions in this new family of universal replication regulators may pave the path to genetic instability and carcinogenesis

Adverse outcome pathways (AOPs) for radiation-induced reproductive effects in environmental species: state of science and identification of a consensus AOP network

Background Reproductive effects of ionizing radiation in organisms have been observed under laboratory and field conditions. Such assessments often rely on associations between exposure and effects, and thus lacking a detailed mechanistic understanding of causality between effects occurring at different levels of biological organization. The Adverse Outcome Pathway (AOP), a conceptual knowledge framework to capture, organize, evaluate and visualize the scientific knowledge of relevant toxicological effects, has the potential to evaluate the causal relationships between molecular, cellular, individual, and population effects. This paper presents the first development of a set of consensus AOPs for reproductive effects of ionizing radiation in wildlife. This work was performed by a group of experts formed during a workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. The work presents a series of taxon-specific case studies that were used to identify relevant empirical evidence, identify common AOP components and propose a set of consensus AOPs that could be organized into an AOP network with broader taxonomic applicability. Conclusion Expert consultation led to the identification of key biological events and description of causal linkages between ionizing radiation, reproductive impairment and reduction in population fitness. The study characterized the knowledge domain of taxon-specific AOPs, identified knowledge gaps pertinent to reproductive-relevant AOP development and reflected on how AOPs could assist applications in radiation (radioecological) research, environmental health assessment, and radiological protection. Future advancement and consolidation of the AOPs is planned to include structured weight of evidence considerations, formalized review and critical assessment of the empirical evidence prior to formal submission and review by the OECD sponsored AOP development program

Using targeted vouchers and health equity funds to improve access to skilled birth attendants for poor women: a case study in three rural health districts in Cambodia

<p>Abstract</p> <p>Background</p> <p>In many developing countries, the maternal mortality ratio remains high with huge poor-rich inequalities. Programmes aimed at improving maternal health and preventing maternal mortality often fail to reach poor women. Vouchers in health and Health Equity Funds (HEFs) constitute a financial mechanism to improve access to priority health services for the poor. We assess their effectiveness in improving access to skilled birth attendants for poor women in three rural health districts in Cambodia and draw lessons for further improvement and scaling-up.</p> <p>Methods</p> <p>Data on utilisation of voucher and HEF schemes and on deliveries in public health facilities between 2006 and 2008 were extracted from the available database, reports and the routine health information system. Qualitative data were collected through focus group discussions and key informant interviews. We examined the trend of facility deliveries between 2006 and 2008 in the three health districts and compared this with the situation in other rural districts without voucher and HEF schemes. An operational analysis of the voucher scheme was carried out to assess its effectiveness at different stages of operation.</p> <p>Results</p> <p>Facility deliveries increased sharply from 16.3% of the expected number of births in 2006 to 44.9% in 2008 after the introduction of voucher and HEF schemes, not only for voucher and HEF beneficiaries, but also for self-paid deliveries. The increase was much more substantial than in comparable districts lacking voucher and HEF schemes. In 2008, voucher and HEF beneficiaries accounted for 40.6% of the expected number of births among the poor. We also outline several limitations of the voucher scheme.</p> <p>Conclusions</p> <p>Vouchers plus HEFs, if carefully designed and implemented, have a strong potential for reducing financial barriers and hence improving access to skilled birth attendants for poor women. To achieve their full potential, vouchers and HEFs require other interventions to ensure the supply of sufficient quality maternity services and to address other non-financial barriers to demand. If these conditions are met, voucher and HEF schemes can be further scaled up under close monitoring and evaluation.</p

Are pain, functional limitations and quality of life associated with objectively measured physical activity in patients with end-stage osteoarthritis of the hip or knee?

Objectives: Physical activity is promoted in patients with hip or knee osteoarthritis (OA), yet little is known about its relationship with symptoms, functional limitations and Quality of Life (QoL). We investigated if OA-associated pain, functional limitations and QoL are associated with objectively measured physical activity in patients with end-stage hip/knee OA. Methods: Cross-sectional study including patients scheduled for primary total hip/knee arthroplasty. Patients wore an accelerometer (Activ8) with physical activity assessed over waking hours, and expressed as number of activity daily counts (ADC) per hour, %time spent on physical activity i.e. walking, cycling or running (%PA), and %time spent sedentary (%SB). Pain, functional limitations and joint-specific and general QoL were assessed with the Hip disability/Knee Injury and Osteoarthritis Outcome Score (HOOS/KOOS) and the Short Form (SF)-12. Multivariate linear regression models with the three to Z-scores transformed parameters of physical activity as dependent variables and adjusted for confounding, were conducted. Results: 49 hip and 48 knee OA patients were included. In hip and knee OA patients the mean number of ADC, %PA and %SB were 18.79 ± 7.25 and 21.19 ± 6.16, 14 ± 6.4 and 15 ± 5.0, and 66 ± 10.5 and 68 ± 8.7, respectively. In hip OA, better joint-specific and general QoL were associated with more ADC, (β 0.028; 95%CI:0.007–0.048, β0.041; 95%CI:0.010–0.071). Also, better general QoL was associated with the %PA (β 0.040, 95%CI:0.007–0.073). No other associations were found. Conclusion: Whereas QoL was associated with physical activity in hip OA, pain and functional limitations were not related to objectively measured physical activity in patients with end-stage hip or knee OA

Use of Genomic DNA as an Indirect Reference for Identifying Gender-Associated Transcripts in Morphologically Identical, but Chromosomally Distinct, Schistosoma mansoni Cercariae

BACKGROUND: The use of DNA microarray technology to study global Schistosoma gene expression has led to the rapid identification of novel biological processes, pathways or associations. Implementation of standardized DNA microarray protocols across laboratories would assist maximal interpretation of generated datasets and extend productive application of this technology. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing a new Schistosoma mansoni oligonucleotide DNA microarray composed of 37,632 elements, we show that schistosome genomic DNA (gDNA) hybridizes with less variation compared to complex mixed pools of S. mansoni cDNA material (R = 0.993 for gDNA compared to R = 0.956 for cDNA during ‘self versus self’ hybridizations). Furthermore, these effects are species-specific, with S. japonicum or Mus musculus gDNA failing to bind significantly to S. mansoni oligonucleotide DNA microarrays (e.g R = 0.350 when S. mansoni gDNA is co-hybridized with S. japonicum gDNA). Increased median fluorescent intensities (209.9) were also observed for DNA microarray elements hybridized with S. mansoni gDNA compared to complex mixed pools of S. mansoni cDNA (112.2). Exploiting these valuable characteristics, S. mansoni gDNA was used in two-channel DNA microarray hybridization experiments as a common reference for indirect identification of gender-associated transcripts in cercariae, a schistosome life-stage in which there is no overt sexual dimorphism. This led to the identification of 2,648 gender-associated transcripts. When compared to the 780 gender-associated transcripts identified by hybridization experiments utilizing a two-channel direct method (co-hybridization of male and female cercariae cDNA), indirect methods using gDNA were far superior in identifying greater quantities of differentially expressed transcripts. Interestingly, both methods identified a concordant subset of 188 male-associated and 156 female-associated cercarial transcripts, respectively. Gene ontology classification of these differentially expressed transcripts revealed a greater diversity of categories in male cercariae. Quantitative real-time PCR analysis confirmed the DNA microarray results and supported the reliability of this platform for identifying gender-associated transcripts. CONCLUSIONS/SIGNIFICANCE: Schistosome gDNA displays characteristics highly suitable for the comparison of two-channel DNA microarray results obtained from experiments conducted independently across laboratories. The schistosome transcripts identified here demonstrate, for the first time, that gender-associated patterns of expression are already well established in the morphologically identical, but chromosomally distinct, cercariae stage

A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.</p> <p>Methods</p> <p>The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.</p> <p>Results</p> <p>For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.</p> <p>Conclusion</p> <p>In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.</p

Exercise therapy and cognitive behavioural therapy to improve fatigue, daily activity performance and quality of life in Postpoliomyelitis Syndrome: the protocol of the FACTS-2-PPS trial

Contains fulltext : 88661.pdf (publisher's version ) (Open Access)BACKGROUND: Postpoliomyelitis Syndrome (PPS) is a complex of late onset neuromuscular symptoms with new or increased muscle weakness and muscle fatigability as key symptoms. Main clinical complaints are severe fatigue, deterioration in functional abilities and health related quality of life. Rehabilitation management is the mainstay of treatment. Two different therapeutic interventions may be prescribed (1) exercise therapy or (2) cognitive behavioural therapy (CBT). However, the evidence on the effectiveness of both interventions is limited. The primary aim of the FACTS-2-PPS trial is to study the efficacy of exercise therapy and CBT for reducing fatigue and improving activities and quality of life in patients with PPS. Additionally, the working mechanisms, patients' and therapists' expectations of and experiences with both interventions and cost-effectiveness will be evaluated. METHODS/DESIGN: A multi-centre, single-blinded, randomized controlled trial will be conducted. A sample of 81 severely fatigued patients with PPS will be recruited from 3 different university hospitals and their affiliate rehabilitation centres. Patients will be randomized to one of three groups i.e. (1) exercise therapy + usual care, (2) CBT + usual care, (3) usual care. At baseline, immediately post-intervention and at 3- and 6-months follow-up, fatigue, activities, quality of life and secondary outcomes will be assessed. Costs will be based on a cost questionnaire, and statistical analyses on GEE (generalized estimated equations). Analysis will also consider mechanisms of change during therapy. A responsive evaluation will be conducted to monitor the implementation process and to investigate the perspectives of patients and therapists on both interventions. DISCUSSION: A major strength of the FACTS-2-PPS study is the use of a mixed methods design in which a responsive and economic evaluation runs parallel to the trial. The results of this study will generate new evidence for the rehabilitation treatment of persons with PPS. TRIAL REGISTRATION: Dutch Trial Register NTR1371