bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II type 1 receptor antagonists alleviate muscle pathology in the mouse model for laminin-α2-deficient congenital muscular dystrophy (MDC1A)
Authors: Meinen Sarina , Lin Shuo , Ruegg Markus A 
Published: September 2012

Abstract

Background
Laminin-α2-deficient congenital muscular dystrophy (MDC1A) is a severe muscle-wasting disease for which no curative treatment is available. Antagonists of the angiotensin II receptor type 1 (AT1), including the anti-hypertensive drug losartan, have been shown to block also the profibrotic action of transforming growth factor (TGF)-β and thereby ameliorate disease progression in mouse models of Marfan syndrome. Because fibrosis and failure of muscle regeneration are the main reasons for the severe disease course of MDC1A, we tested whether L-158809, an analog derivative of losartan, could ameliorate the dystrophy in dy

W

/dy

W
mice, the best-characterized model of MDC1A.

Methods
L-158809 was given in food to dy

W

/dy

W
mice at the age of 3 weeks, and the mice were analyzed at the age of 6 to 7 weeks. We examined the effect of L-158809 on muscle histology and on muscle regeneration after injury as well as the locomotor activity and muscle strength of the mice.

Results
We found that TGF-β signaling in the muscles of the dy

W

/dy

W
mice was strongly increased, and that L-158809 treatment suppressed this signaling. Consequently, L-158809 reduced fibrosis and inflammation in skeletal muscle of dy

W

/dy

W
mice, and largely restored muscle regeneration after toxin-induced injury. Mice showed improvement in their locomotor activity and grip strength, and their body weight was significantly increased.

Conclusion
These data provide evidence that AT1 antagonists ameliorate several hallmarks of MDC1A in dy

W

/dy

W
mice, the best-characterized mouse model for this disease. Because AT1 antagonists are well tolerated in humans and widely used in clinical practice, these results suggest that losartan may offer a potential future treatment of patients with MDC1A.
Thioredoxin, oxidative stress, cancer and aging
Authors: Flores Lisa C , Ortiz Melanie , Dube Sara , Hubbard Gene B , Lee Shuko , Salmon Adam , Zhang Yiqiang , Ikeno Yuji 
Published: September 2012

Abstract
The Free Radical or Oxidative Stress Theory of Aging is one of the most popular theories in aging research and has been extensively studied over the past several decades. However, recent evidence using transgenic/knockout mice that overexpress or down-regulate antioxidant enzymes challenge the veracity of this theory since the animals show no increase or decrease in lifespan. These results seriously call into question the role of oxidative damage/stress in the aging process in mammals. Therefore, the theory requires significant modifications if we are to understand the relationship between aging and the regulation of oxidative stress. Our laboratory has been examining the impacts of thioredoxins (Trxs), in the cytosol and mitochondria, on aging and age-related diseases. Our data from mice that are either up-regulating or down-regulating Trx in different cellular compartments, that is, the cytosol or mitochondria, could shed some light on the role of oxidative stress and its pathophysiological effects. The results generated from our lab and others may indicate that: 1) changes in oxidative stress and the redox state in the cytosol, mitochondria or nucleus might play different roles in the aging process; 2) the role of oxidative stress and redox state could have different pathophysiological consequences in different tissues/cells, for example, mitotic vs. post-mitotic; 3) oxidative stress could have different pathophysiological impacts in young and old animals; and 4) the pathophysiological roles of oxidative stress and redox state could be controlled through changes in redox-sensitive signaling, which could have more diverse effects on pathophysiology than the accumulation of oxidative damage to various molecules. To critically test the role of oxidative stress on aging and age-related diseases, further study is required using animal models that regulate oxidative stress levels differently in each cellular compartment, each tissue/organ, and/or at different stages of life (young, middle and old) to change redox sensitive signaling pathways.
ParameciumBBS genes are key to presence of channels in Cilia
Authors: Valentine Megan Smith , Rajendran Anbazhagan , Yano Junji , Weeraratne S Dilhan , Beisson Janine , Cohen Jean , Koll France , Van Houten Judith 
Published: September 2012

Abstract

Background
Changes in genes coding for ciliary proteins contribute to complex human syndromes called ciliopathies, such as Bardet-Biedl Syndrome (BBS). We used the model organism Paramecium to focus on ciliary ion channels that affect the beat form and sensory function of motile cilia and evaluate the effects of perturbing BBS proteins on these channels.

Methods
We used immunoprecipitations and mass spectrometry to explore whether Paramecium proteins interact as in mammalian cells. We used RNA interference (RNAi) and swimming behavior assays to examine the effects of BBS depletion on ciliary ion channels that control ciliary beating. Combining RNA interference and epitope tagging, we examined the effects of BBS depletion of BBS 7, 8 and 9 on the location of three channels and a chemoreceptor in cilia.

Results
We found 10 orthologs of 8 BBS genes in P. tetraurelia. BBS1, 2, 4, 5, 7, 8 and 9 co-immunoprecipitate. While RNAi reduction of BBS 7 and 9 gene products caused loss and shortening of cilia, RNAi for all BBS genes except BBS2 affected patterns of ciliary motility that are governed by ciliary ion channels. Swimming behavior assays pointed to loss of ciliary K+ channel function. Combining RNAi and epitope tagged ciliary proteins we demonstrated that a calcium activated K+ channel was no longer located in the cilia upon depletion of BBS 7, 8 or 9, consistent with the cells’ swimming behavior. The TRPP channel PKD2 was also lost from the cilia. In contrast, the ciliary voltage gated calcium channel was unaffected by BBS depletion, consistent with behavioral assays. The ciliary location of a chemoreceptor for folate was similarly unperturbed by the depletion of BBS 7, 8 or 9.

Conclusions
The co-immunoprecipitation of BBS 1,2,4,5,7,8, and 9 suggests a complex of BBS proteins. RNAi for BBS 7, 8 or 9 gene products causes the selective loss of K+ and PKD2 channels from the cilia while the critical voltage gated calcium channel and a peripheral receptor protein remain undisturbed. These channels govern ciliary beating and sensory function. Importantly, in P. tetraurelia we can combine studies of ciliopathy protein function with behavior and location and control of ciliary channels.
Cost analysis of HIV treatment and drug-related adverse events when fixed-dose combinations of antiretrovirals (FDCs) were stopped, versus continuation with FDCs
Authors: Homar Francesc , Lozano Virginia , Martínez-Gómez Juan , Oyagüez Itziar , Pareja Antonio , Payeras Antoni , Serrano Joaquín , Carratalá Carmen , Casado Miguel Ángel 
Published: September 2012

Abstract

Background
The lower sales price of generic lamivudine has caused healthcare administrators to consider abolishing fixed-dose antiretroviral combinations (FDCs) that contain lamivudine and emtricitabine. The alternative is to administer the individual components of the FDCs separately, thus incorporating the new generic lamivudine medication.

Methods
The Balearic Islands Health Service ordered the discontinuation of the treatment with FDCs in July 2010, but FDCs were reintroduced in August 2010. At that point, an independent, retrospective cost analysis was performed by Son Llàtzer Hospital. A total of 75 patients who were treated from July to August 2010 underwent replacement of their FDC treatment with the individual components. Additionally, 150 patients who continued using FDCs were randomly selected. For both patient groups, the antiretroviral therapy that was administered and the costs associated with management of adverse events were recorded. The study period used for the cost calculations was the average number of days that patients used separate components of FDCs (120 days). An alternative analysis was performed to consider the costs of the extra follow-up visit (consultation and clinical tests) that was required for patients who changed their antiretroviral therapy.

Results
Considering antiretroviral therapies and adverse events, the administration of the separate components increased the total daily cost by 0.72 € per patient compared to treatment with FDCs. When the cost of an extra follow-up visit was considered, the daily cost increased by 3.61 € per patient.

Conclusions
Our study suggests that the discontinuation of FDC treatment and the replacement with the administration of separate antiretroviral agents could lead to an increase in healthcare costs due to the higher rate of adverse events that was observed with the discontinuation of FDCs.
Estimating cost-effectiveness in public health: a summary of modelling and valuation methods
Authors: Marsh Kevin , Phillips Ceri J , Fordham Richard , Bertranou Evelina , Hale Janine 
Published: September 2012

AbstractIt is acknowledged that economic evaluation methods as they have been developed for Health Technology Assessment do not capture all the costs and benefits relevant to the assessment of public health interventions. This paper reviews methods that could be employed to measure and value the broader set of benefits generated by public health interventions. It is proposed that two key developments are required if this vision is to be achieved. First, there is a trend to modelling approaches that better capture the effects of public health interventions. This trend needs to continue, and economists need to consider a broader range of modelling techniques than are currently employed to assess public health interventions. The selection and implementation of alternative modelling techniques should be facilitated by the production of better data on the behavioural outcomes generated by public health interventions. Second, economists are currently exploring a number of valuation paradigms that hold the promise of more appropriate valuation of public health interventions outcomes. These include the capabilities approach and the subjective well-being approach, both of which offer the possibility of broader measures of value than the approaches currently employed by health economists. These developments should not, however, be made by economists alone. These questions, in particular what method should be used to value public health outcomes, require social value judgements that are beyond the capacity of economists. This choice will require consultation with policy makers, and perhaps even the general public. Such collaboration would have the benefit of ensuring that the methods developed are useful for decision makers.
Chemical composition and antibacterial activity of the essential oils of Ferula vesceritensis Coss et Dur. leaves, endemic in Algeria
Authors: Zellagui Amar , Gherraf Noueddine , Rhouati Salah 
Published: September 2012

Abstract

Background
The biological importance of members of genus Ferula promoted us to investigate the leaves of Ferula vesceritensis Coss et Dur. (endemic plant) previously not investigated. This study presents the chemical composition and antibacterial activities of the hydrodistilled oils.

Results
Volatile components of the leaves of F. vesceritensis have been studied by gas chromatography–mass spectrometry to afford 23 compounds. The major components were found to be 5,9-tetradecadiyne (24.72%), germacrene D (24.51%), farnesene (8.57%), and α-bisabolene (8.57%). The antimicrobial activities of the essential oils were evaluated by disk diffusion method and tested against Gram-positive and Gram-negative bacteria. The volatile oil showed a strong antibacterial activity against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia.

Conclusions
These results reinforce the previous studies showing that the genus Ferula is considered as a good source of essential oils. The results presented here can be considered as the first information on the antimicrobial properties of F. vesceritensis.
Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 1)
Authors: Owens David Cunningham 
Published: September 2012

SummaryA number of pragmatic trials have cast doubt on the concept of ‘atypicality’ in relation to antipsychotic drugs, and some commentators have argued that the dichotomy between ‘typical’ (‘first-generation’) and ‘atypical’ ('second-generation’) compounds is artificial and should be abandoned, leaving the entire class of antipsychotics available for consideration in more individualised treatment planning. However, younger psychiatrists now gain little or no experience in the use of older antipsychotics. This is the first of two articles addressing practical issues for consideration in prescribing the older antipsychotics available in the UK. It covers background, including the fundamental clinical action of antipsychotics, the nature of drug licensing and identification of pharmacological parameters that may be of value in prescribing decisions, and discusses the phenothiazines: chlorpromazine, promazine, levomepromazine, pericyazine, perphenazine, trifluoperazine and prochlorperazine.
Telemental health: videoconferencing in mental health services
Authors: Vaitheswaran Sridhar , Crockett Philip , Wilson Sam , Millar Harry 
Published: September 2012

SummaryVideo technology was first used in psychiatric services in the 1950s but came into general use in the 1990s, particularly in North America and Australia. Video has utility across all ages and in a wide range of clinical situations. These include case conferencing for patients with complex problems (e.g. when planning discharge from specialist inpatient units), psychological assessment and treatment, Mental Health Act assessments, suicide risk assessment and work in forensic settings. Potential for benefit may be most obvious in remote locations, but video use is also relevant in urban settings. Lack of training and experience, inadequate access to equipment and insufficient technical support have all limited the take-up of this technology in the UK. This article briefly reviews the literature and outlines technical and cost considerations when using video technology. Three services in Scotland are described to illustrate ways in which videoconferencing can enhance services.
Meet the relatives: a reintroduction to the clinical pharmacology of ‘typical’ antipsychotics (Part 2)
Authors: Owens David Cunningham 
Published: September 2012

SummaryThis second of two articles on the ‘typical’ (‘first-generation’) antipsychotics covers non-phenothiazines: thioxanthenes (flupentixol and zuclopenthixol), butyrophenones/diphenylbutylpiperidines (including one-time world market-leader haloperidol, and pimozide) and sulpiride, for many years the only substituted benzamide available in the UK. Several tolerability issues ascribed specifically or more frequently to older antipsychotics are also discussed.
The price of a drink: the potential of alcohol minimum unit
pricing as a public health measure in the UK
Authors: Rice Peter , Drummond Colin 
Published: September 2012

SummaryThe UK has seen a dramatic increase in alcohol consumption and
alcohol-related harm over the past 30 years. Alcohol taxation has long been
considered a key method of controlling alcohol-related harm but a
combination of factors has recently led to consideration of methods which
affect the price of the cheapest alcohol as a means of improved targeting of
alcohol control measures to curb the consumption of the heaviest drinkers.
Although much of the evidence in favour of setting a minimum price of a unit
of alcohol is based on complex econometric models rather than empirical
data, all jurisdictions within the UK now intend to make selling alcohol
below a set price illegal, which will provide a naturalistic experiment
allowing assessment of the impact of minimum pricing.
Child abuse and neglect: a major public health issue and the role of child and adolescent mental health services
Authors: Shaw Mike , De Jong Margaret 
Published: September 2012

SummaryChild and adolescent mental health services (CAMHS) make an important contribution to the assessment and treatment of abuse and neglect in children. However, the provision of services is patchy and we see the present political and economic environment as providing opportunities but also threats. In this editorial we examine some of the barriers to CAMHS involvement, emphasise the potential public health benefits of improving the service, and provide some examples of how CAMHS could develop its involvement in partnership with Social Services and the family courts.
Prevalence of perceived coercion among psychiatric patients: literature review and meta-regression modelling
Authors: Newton-Howes Giles , Stanley James 
Published: September 2012

Aims and methodTo assess how common the subjective experience of coercion is in psychiatric care and what affects its prevalence. A review of published data was undertaken to assess prevalence of coercion and potential confounding variables. The heterogeneity of results was studied using meta-regression to quantify the relative impact of four potential explanatory variables.ResultsThe raw prevalence of perceived coercion ranged from 16 to 90%. A quarter of legally detained patients did not feel coerced into psychiatric care, whereas a quarter of voluntary in-patients reported coercion in care. Coercion was more common in studies outside the USA, among patient populations subject to legal detention and populations studied using the MacArthur Perceived Coercion Scale as opposed to other measures. Timing of the interview was not associated with coercion.Clinical implicationsCoercion in psychiatric care remains highly prevalent but varies widely by study. Consistency in measurement is necessary to allow better comparison between studies.
What can we learn from service user memoirs? Information and service user experience
Authors: Armstrong Neil 
Published: September 2012

SummaryService user memoirs are frequently reviewed in The Psychiatrist and other related journals. Some academic publications include first-hand accounts of mental ill health, and there is a lively market for autobiographical books and articles about mental illness. But clinicians already have extensive contact with service users and it might seem unlikely that they have much to gain from reading memoirs. In this article I suggest that the greater depth of reflection in published memoirs means clinicians do in fact have something to learn. I illustrate my argument by showing how memoirs cast a light on the world of information and conclude by suggesting reasons why memoirs raise issues that are of increasing clinical importance.
Biomarkers in primary open angle glaucoma
Authors: Kokotas Haris , Kroupis Christos , Chiras Dimitrios , Grigoriadou Maria , Lamnissou Klea , Petersen Michael B. , Kitsos George 
Published: September 2012

Abstract
Glaucoma, a leading cause of blindness worldwide, is currently defined as a disturbance of the structural or functional integrity of the optic nerve that causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. This disturbance usually can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Glaucoma can be divided roughly into two main categories, ‘open angle’ and ‘closed angle’ glaucoma. Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice loss of vision until the disease has progressed significantly. Primary open angle glaucoma (POAG) is described distinctly as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and IOP that is too high for the healthy eye. It manifests by cupping and atrophy of the optic disc, in the absence of other known causes of glaucomatous disease. Several biological markers have been implicated with the disease. The purpose of this study was to summarize the current knowledge regarding the non-genetic molecular markers which have been predicted to have an association with POAG but have not yet been validated.
The high-sensitivity cardiac troponin T assay is superior to its previous assay generation for prediction of 90-day clinical outcome in ischemic stroke
Authors: Furtner Martin , Ploner Thomas , Hammerer-Lercher Angelika , Pechlaner Raimund , Mair Johannes 
Published: September 2012

Abstract

Background: Cardiac troponin T (cTnT) has been reported to be a predictor of stroke outcome. We hypothesized that the high-sensitivity cTnT (hs-cTnT) assay is superior to its previous assay generation for stroke outcome prediction.

Methods: cTnT was measured on emergency department admission in 60 consecutive patients (35 males, age 69.4±13.9 years) with ischemic stroke. Adverse 90-day clinical outcome was defined as death or dependence (modified Rankin scale ≥3 or Barthel index <75).

Results: Stroke aetiology was microangiopathy in three, macroangiopathy in 17, cardiac embolism in 26, dissection in one and unknown in 13 patients. At 90-day follow-up 16 (27%) patients had an adverse outcome. Receiver operating characteristics (ROC) curve analysis yielded a significantly better performance of hs-cTnT vs. cTnT (area under ROC curve: 0.80 [95% CI 0.68–0.89] vs. 0.70 [95% CI 0.57–0.82], p=0.017). The optimal discriminator values according to ROC analysis were 5.1 ng/L (hs-cTnT assay) and 11 ng/L (4th generation cTnT assay) with: sensitivities 94% vs. 56%, specificities 57% vs. 84%, positive predictive values 44% vs. 56%, and negative predictive values 96% vs. 84%.

Conclusions: Improvements in cTnT assay sensitivity and precision at the low measuring range resulted in a more accurate prediction of ischemic stroke outcome, particularly for ruling out worse outcome.
Reducing the number of clinical stat phlebotomy orders: feasible or not?
Authors: Scherrenburg Jolanda , van de Wijngaart Dennis J. , Janssens Pim M.W. 
Published: September 2012

AbstractBackground:To manage the costs and performance of diagnostic services involving laboratory testing permanent evaluation is required. Among these, the ever increasing use of stat ordering, involving labour intensive phlebotomy, warrants explanation, especially for a phlebotomy service organised by the laboratory, not by those responsible for and/or carrying out the requests, such as doctors and nurses.Methods:To explore the possibilities to reduce the number of stat phlebotomy requests, we conducted a survey among nurses and doctors of their motives in requesting 109 randomly selected stat orders.Results:Fifty-five percent of all stat phlebotomy orders were requested for immediate decision-making with respect to urgently required diagnosis and patient care, defined by us as medical reasons. The other 45% of the stat orders were made for logistical reasons relating to the patient care or the hospital organisation. In total, 19 phlebotomy requests (17%) were unnecessary and could have been avoided. For most of the stat phlebotomy orders alternatives were not possible, as only 2% of the requests could have been replaced by analysis in material that had been withdrawn earlier.Conclusions:The majority of the stat orders for phlebotomy were requested for good reasons, about equally distributed among the medical and logistical needs. This sets limits to the measures being feasible to further improve stat phlebotomy ordering efficiency, taking into account the way of functioning of modern hospital care.