366 research outputs found
Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency
In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation
User-centered virtual environment design for virtual rehabilitation
<p>Abstract</p> <p>Background</p> <p>As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy.</p> <p>Methods</p> <p>An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design.</p> <p>Results</p> <p>The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations.</p> <p>Conclusions</p> <p>The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.</p
Cancer-related fatigue: clinical practice versus practice guidelines
Purpose This study investigated adherence to treatment guidelines on cancer-related anaemia and fatigue (CRA/CRF) and factors influencing the choice of intervention. Methods In this prospective, observational study, 136 cancer patients being treated with chemotherapy in a large community hospital completed a questionnaire at consecutive outpatient visits assessing fatigue (the Functional Assessment of Chronic Illness Therapy—Fatigue) and fatigue-related counselling and advice received. Data on administration of chemotherapy and use of epoetin or blood transfusions were abstracted from the medical records. Results Fifty-three percent of patients with severe anaemia (Hb<10 g/dl) and 6% of patients with less severe anaemia (Hb levels 10-12 g/dl) received treatment (epoetin and/or blood transfusions). Half of the patients with less severe anaemia reported clinically relevant levels of fatigue. More than 50% of all patients received fatigue-related counselling, primarily at the start of chemotherapy. Most counselling was directed at energy conservation. Fatigue was not associated significantly with the use of epoetin or blood transfusion. Patients receiving palliative treatment (17%), male patients (16%) and patients with a low Hb level (<6.2 g/dl, 38%) were treated significantly more often with epoetin. Conclusions In daily clinical practice, guidelines concerning the use of epoetin or blood transfusion in severe CRA are adhered to in about half of the cases. In patients with less severe anaemia, the level of fatigue did not play a significant role in the use of epoetin. According to current guidelines, counselling on CRF should be directed primarily at activity enhancement. However, only a minority of patients receive such counselling
Ribosomal oxygenases are structurally conserved from prokaryotes to humans
2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases
Child Care Time, Parents’ Well-Being, and Gender: Evidence from the American Time Use Survey
This study used data from the ‘Well Being Module’ of the 2010 American Time Use Survey (N = 1699) to analyze how parents experience child care time in terms of meaning and stress levels. Multivariate multilevel regressions showed clear differences by gender and the circumstances of child care activities. Mothers experienced child care time as more stressful than fathers, and fathers as slightly more meaningful. Interactive child care was experienced as more meaningful and less stressful than routine child care, whereas these differences were stronger among fathers than among mothers. Mothers experienced child care with a minor child as highly meaningful, and with an adolescent as particularly stressful. Fathers experienced child care with an infant as highly stressful, and with an offspring in middle childhood as disproportionally meaningful. The spouse’s presence was moderately associated with higher senses of meaning and lower levels of stress during child care, but these differences were modest, and only visible among fathers. Paid work hours increased mothers’ stress levels during child care activities, but reduced fathers’ stress levels. Meanwhile, nonemployed fathers reported child care time as less meaningful than non-employed mothers. Overall, this study has important scientific and practical implications for `understanding the gendered nature of parents’ child care time and well-being
Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for various malignant and non-malignant diseases. Many patients have now been followed for two or three decades posttransplant and are presumed to be cured. With the tremendous advances achieved in terms of supportive care, it is reasonable to expect outcomes to improve steadily and consequently increasing numbers of transplant survivors will be facing life after the initial transplant experience. Although long-term allo-HSCT survivors generally enjoy good health, for many others, cure or control of the underlying disease is not accompanied by full restoration of health. The burden of long-term morbidity borne by allo-HSCT survivors is substantial, and long-term follow-up of patients who received allo-HSCT is now widely recommended. Immediate survival is no longer the sole concern after allo-HSCT. The goals should also include complete recovery of the overall health status with normal physical and psychological functioning. Long-term side effects after allo-HSCT include non-malignant organ or tissue dysfunction, changes in quality of life, infections related to abnormal immune reconstitution and secondary cancers. Many of these can be attributed to the deleterious effects of chronic graft-versus-host disease. The aims of this review are to provide an update on the recent research evidence in the field
Response to 2009 Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Patients and the Influence of Prior Seasonal Influenza Vaccination
Background: The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:NCT01066169) Methods and Findings: In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis) was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21). Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI) assay. The seroprotection rate (defined as HI titers ≥1:40) for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We fou
Autoimmune and autoinflammatory mechanisms in uveitis
The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
Adenosine-stress cardiac magnetic resonance imaging in suspected coronary artery disease: a net cost analysis and reimbursement implications
The health and economic implications of new imaging technologies are increasingly relevant policy issues. Cardiac magnetic resonance imaging (CMR) is currently not or not sufficiently reimbursed in a number of countries including Germany, presumably because of a limited evidence base. It is unknown, however, whether it can be effectively used to facilitate medical decision-making and reduce costs by serving as a gatekeeper to invasive coronary angiography. We investigated whether the application of CMR in patients suspected of having coronary artery disease (CAD) reduces costs by averting referrals to cardiac catheterization. We used propensity score methods to match 218 patients from a CMR registry to a previously studied cohort in which CMR was demonstrated to reliably identify patients who were low-risk for major cardiac events. Covariates over which patients were matched included comorbidity profiles, demographics, CAD-related symptoms, and CAD risk as measured by Morise scores. We determined the proportion of patients for whom cardiac catheterization was deferred based upon CMR findings. We then calculated the economic effects of practice pattern changes using data on cardiac catheterization and CMR costs. CMR reduced the utilization of cardiac catheterization by 62.4%. Based on estimated catheterization costs of € 619, the utilization of CMR as a gatekeeper reduced per-patient costs by a mean of € 90. Savings were realized until CMR costs exceeded € 386. Cost savings were greatest for patients at low-risk for CAD, as measured by baseline Morise scores, but were present for all Morise subgroups with the exception of patients at the highest risk of CAD. CMR significantly reduces the utilization of cardiac catheterization in patients suspected of having CAD. Per-patient savings range from € 323 in patients at lowest risk of CAD to € 58 in patients at high-risk but not in the highest risk stratum. Because a negative CMR evaluation has high negative predictive value, its application as a gatekeeper to cardiac catheterization should be further explored as a treatment option
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