Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on emerging drug therapies for systemic lupus erythematosus

Importance of the field: Despite the improvement in survival of systemic lupus erythematosus (SLE), a cure for this chronic and disabling disease is still a myth. Refractory manifestations and treatment-related complications are still major causes for mortality and morbidity. More effective but less toxic therapies through modification of existing regimens, combination strategies or more specific targeting at the immunopathogenetic pathways are necessary. Areas covered in this review: The availability of biotechnology has led to the emergence of targeted therapies for SLE. In the past 5 years, there have been a number of clinical trials in the pipeline that involve existing drugs or novel biological agents. This article updates different novel therapeutic approaches in SLE that have emerged since 2006. What the readers will gain: Readers will read the latest information and critical appraisals regarding recent clinical trials in lupus. Expert opinions on future directions of SLE treatment trials are also provided. Take home message: SLE is a clinically and immunologically heterogeneous disease. Targeted therapies are currently available but to the disappointment of the lupus community, data from many recent clinical trials are unfavorable. While flaws and limitations in the study design and outcome measures may contribute to the futility of these trials, selection of SLE subsets by serum and cellular biomarkers may identify those who will benefit from these targeted therapies.
Effects of supplementing pregnant heifers with methionine or melatonin on the anatomy and other characteristics of their lateral hind claws

Three groups of four primiparous Holstein-Friesian heifers were fed throughout pregnancy either a control diet or that diet supplemented with either 5 to 6 g per day of rumen-protected intestinally available methionine or 25 mg melatonin. They were euthanased three days after calving. The dietary supplements had no effect on the impression hardness or the concentrations of cysteine and methionine in samples of claw horn collected from a range of sites, or on the areas of erosion in the sole and heel. Significant differences were recorded for the hardness of the horn in the order wall>sole>heel. These differences were associated with higher concentrations of cysteine and lower concentrations of methionine in samples of horn from the dorsal wall than in samples from the prebulbar region of the sole. There were no significant differences attributable to the dietary supplements in the soft tissue anatomy of the solear dermis and epidermis.
A Clinical Approach to Diagnosis and Management of Paget's Disease of Bone

PAGET’S DISEASE of bone (osteitis deformans) is a focal disorder of accelerated skeletal remodeling that can involve a single bone (monostotic) or multiple bones (polyostotic) and leads to bone hypertrophy, cortical expansion, and an abnormal bone structure responsible for bone pain and bone deformity and skeletal fragility. Complications of this disease can involve bones (deformity, fracture, and neoplastic degeneration), joints (osteoarthritis), the nervous system, and the vascular system. (1)
Supply Function Equilibria in Networks with Transport Constraints

Transport constraints limit competition and arbitrageurs possibilities of exploiting price differences between commodities in neighbouring markets. We analyze a transport-constrained network with local demand shocks, where spatially distributed oligopoly producers compete with supply functions, as in wholesale electricity markets. Uniqueness and existence results are proven, and we are able to explicitly solve for symmetric supply-function equilibria in some special cases.
Retrospective study on the impact of hepatitis C virus infection on kidney transplant patients over 20 years.

BACKGROUND The majority of chronic hepatitis is ascribable to hepatitis C virus (HCV) infection, whereas the clinical impact has not been understood in kidney transplant recipients. Our current study was carried out to assess the impact of HCV infection on kidney recipients over the long-term, and to investigate the effect and risk of interferon-alpha (IFN-alpha) therapy for chronic active hepatitis C. METHODS Hepatitis B surface antigen (HBsAg) and antibody to HCV (HCVAb) were examined prospectively and retrospectively in 280 patients, who underwent kidney transplants in the period from 1973 to 1996. The patient survival rate, the graft survival rate, the incidence of liver dysfunction and the cause of mortality among the HCV infected and noninfected groups were analyzed. IFN-alpha therapy was performed on 10 patients with chronic active hepatitis C. RESULTS Prevalence of the hepatitis virus was quite high at 34.3% (96/280): the frequency of the HBsAg carrier was 3.2% (9/280), that of the HCVAb carrier was 28.6% (80/280) and that of the both carriers was 2.5% (7/280). The other 184 cases (65.7%) were negative for both HBsAg and HCVAb. Liver dysfunction developed at the significantly higher incidence of 55% in HCVAb carriers compared to the 9.2% of the noninfected group (P<0.01). HCVAb carriers had a poor survival rate in the second decade compared to the noninfected group: 83.7% vs. 88.91% for 10-year survival (P=0.44) and 63.9% vs. 87.9% for 20-year survival (P<0.05). The poor survival rate was a result of the mortality from liver disorder. Five patients died of such disease in the infected groups whereas no noninfected patient died in the same period (p<0.01). As the result of IFN-alpha therapy, biochemical activity normalized or improved in eight cases, whereas the HCV-RNA titer was reduced only in three patients. Only one patient maintained normal biochemical markers and undetectable levels of HCV-RNA for 2 years after treatment. The therapy was discontinued for five patients with the adverse effects of acute rejection, deterioration of diabetes, and depression. CONCLUSIONS HCV infection has a significant impact on kidney transplant recipients over the long term and in particular affects them in the second decade. Our pilot study revealed only partial efficacy of IFN-alpha therapy for HCV-infected recipients, but with the high risk of acute rejection.
An Etomidate Analogue With Less Adrenocortical Suppression, Stable Hemodynamics, and Improved Behavioral Recovery in Rats

BACKGROUND: ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue designed to alleviate the adrenocortical suppression caused by etomidate while retaining the rapid sedative-hypnotic onset and stable hemodynamic features of etomidate. This study compared the anesthetic effect, hemodynamic stability, and recovery profiles of ET-26HCl, etomidate, and the sedative-hypnotic drug propofol in rats. METHODS: The metabolic half-life of ET-26HCl was determined in vitro using high performance liquid chromatography analysis of samples of rat plasma and liver homogenates taken from 3 animals. Hypnotic median effective doses (HD50) of ET-26HCl, etomidate, and propofol were determined by up-and-down methods. Anesthesia effect and mean arterial pressure were estimated using equivalent intravenous (IV) doses of propofol, etomidate, and ET-26HCl in the rats. Serum concentrations of corticosterone were analyzed by enzyme-linked immunosorbent assay. The ability of rats to recover from the sedative-hypnotic effects of the drugs was evaluated using open field and Morris water maze tests at equipotent doses of propofol, etomidate, ET-26HCl, and normal saline. RESULTS: The metabolic half-life of ET-26HCl was 81 ± 6 minutes in rat plasma and 126 ± 12 minutes in incubation liver homogenate (mean ± standard deviation), respectively. In vivo experiments showed that the potency of ET-26HCl to cause a loss of righting reflex in rats was 3 times lower than that of etomidate in the rats. IV propofol caused a greater decrease in mean arterial pressure relative to the baseline (−27.9 mm Hg) than did ET-26HCl (−10.7 mm Hg) and etomidate (−19.4 mm Hg) at equipotent doses. Serum corticosterone levels after drug administration were significantly higher in the ET-26HCl group than in the etomidate group at equivalent doses when measured 15 (P < .001), 30 (P < .001), and 60 (P = .002) minutes after stimulation with adrenocorticotropic hormone (ACTH1–24). Recovery of spatial orientation from anesthesia induced by an IV bolus injection was faster with ET-26HCl than with propofol, but recovery of spontaneous activity was slower. CONCLUSIONS: ET-26HCl has anesthetic potency and hemodynamic stability similar to etomidate, but it caused less adrenocortical hormone synthesis suppression than etomidate and faster spatial orientation recovery from anesthesia than propofol, which was similar to etomidate.
Influence of volcanic history on groundwater patterns on the west slope of the Oregon High Cascades

Spring systems on the west slope of the Oregon High Cascades exhibit complex relationships among modern topography, lava flow geometries, and groundwater flow patterns. Seven cold springs were continuously monitored for discharge and temperature in the 2004 water year, and they were periodically sampled for δ18O, δD, tritium, and dissolved noble gases. Anomalously high unit discharges suggest that topographically defined watersheds may not correspond to aquifer boundaries, and oxygen isotope data reveal that mean recharge elevations for the springs are coincident with extensive Holocene lava fields. The 3He/4He ratios in most of the springs are close to atmospheric, implying shallow flow paths, and aquifer thicknesses are estimated to be 30–140 m. Estimates using 3H/3He data with exponential and gamma distributions yield mean transit times of ∼3–14 years. Recharge areas and flow paths are likely controlled by the geographic extent of lava flows, and some groundwater may cross the Cascade crest.
[Psychosocial work factors associated to blood pressure and cardiovascular symptoms among Mexican nurses].

OBJECTIVE To determine if job stress, according with Karasek's model, and job insecurity are significantly associated with cardiovascular indicators such as blood pressure (BP) and cardiovascular symptoms (CS), considering traditional risk factors for cardiovascular disease (age, body mass index, smoking, alcohol consumption, among others). MATERIAL AND METHODS A job content questionnaire (JCQ) and one for cardiovascular symptoms were administered to a sample of 109 nurses from a public hospital in Mexico City during July 2004. A digital monitor was utilized to measure BP at the workplace using a point estimates protocol. RESULTS A significant association among these variables was found (beta between .20 and .24), even when traditional cardiovascular risk factors were considered. CONCLUSIONS The relation between job stress and BP is significant in the Mexican population and highlights the association between job insecurity and cardiovascular indicators, indicating its importance in the Mexican work context. Future studies are suggested, as well as the prevention and surveillance of these factors in occupational and public health fields in terms of their role in cardiovascular epidemiology.
Point: HOMA—Satisfactory for the Time Being

There is no doubt that the cluster of clinical and metabolic features associated with insulin resistance predicts risk of developing type 2 diabetes and cardiovascular disease (CVD) (1); however, whether there is merit in defining a syndrome is less clear (2). There is also a lack of agreement regarding the value of measuring insulin sensitivity in clinical practice (3). The widely used criteria for defining the metabolic syndrome (those recommended by the World Health Organization [4] and the Adult Treatment Panel III [5]) includes a measure of insulin resistance in the definition of the syndrome. A very recent approach suggested by a group representing the International Diabetes Federation involves identifying individuals with central obesity and a range of clinical and metabolic parameters associated with insulin resistance; however, it does not include a direct measure of insulin sensitivity (6). It is argued that measures of insulin resistance do not predict CVD when other more easily measured components of the metabolic syndrome cluster are present, and these measures based on fasting insulin are unreliable (3). However, measurement of insulin sensitivity has greatly enhanced the understanding of the pathophysiology of diabetes and relationships to cardiovascular outcomes (7). Dismissing the assessment of insulin sensitivity because its measurement is too variable or difficult (3) is understandable, but hardly desirable, as one major dimension of altered metabolism will be omitted from research and clinical assessments. It may prove to be much the same as assessing cardiovascular risk without serum cholesterol. A truly reliable simple measure may prove to be more appropriate than an aggregation of surrogates in predicting subsequent development of diabetes and CVD and in further explaining disease progression and response to treatment. Several reviews (8,9) describe some of the numerous methods for measuring or estimating insulin sensitivity. The …
Epidural versus non-epidural analgesia for pain relief in labour.

BACKGROUND Epidural analgesia is effective in reducing labour pain, but the possible adverse effects are not clear. OBJECTIVES The objective of this review was to assess the effects of epidural analgesia on pain relief and adverse effects in labour. SEARCH STRATEGY The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA Randomised trials comparing epidural analgesia with other forms of analgesia not involving regional blockade, or no intervention. DATA COLLECTION AND ANALYSIS Eligibility and trial quality were assessed by one reviewer. Study authors were contacted for additional information. MAIN RESULTS Eleven studies involving 3157 women were included. Epidural analgesia was associated with greater pain relief than non-epidural methods, but also with longer first and second stages of labour, an increased incidence of fetal malposition, and increased use of oxytocin and instrumental vaginal deliveries. With new trial data included, no statistically significant effect on caesarean section rates could be identified. REVIEWER'S CONCLUSIONS Epidural analgesia appears to be very effective in reducing pain during labour, although there appear to be some potentially adverse effects. Further research is needed to investigate adverse effects and to evaluate the different techniques used in epidural analgesia.
Effects of Single Trial of Heart-Rate Biofeedback during Ramp Bicycling Exercise

We examined whether a single trial of heart-rate biofeedback was effective to attenuate heart-rate responses during ramp exercise despite a lack of biofeedback conditioning. 35 healthy women exercised in two trials while they tried to attenuate their heart rate by watching biofeedback signals or they only exercised without biofeedback signals (Control trial). 17 subjects were able to attenuate the heart rate during Biofeedback trial (Can group) whereas the remaining subjects were not (Cannot group). In the Can group, the magnitude of heart-rate attenuation in all exercise time was equivalent to 11 ±3% of the preexercise heart rate. Since the heart-rate reduction was similar to that achieved after the heart-rate biofeedback conditioning in previous studies, it is likely that the single trial of heart-rate biofeedback was effective for almost half the subjects to attenuate the heart-rate responses during ramp exercise.
Public Funding of Higher Education: Who Gains, Who Loses?

This paper analyses the effects of public funding of higher education on the welfare of the different agents. It takes into account the hierarchical nature of the educational system and also the fact that parents always have the possibility to complement basic public education with private expenditures in individual tutoring. It is obtained that although public funding implies a larger access to higher education it is always the case that some of the agents that gain access lose in welfare terms. Moreover, it is shown that the marginal agent to access university would always prefer a pure private funding system. Thus, when studying the effects of public funding of higher education, we can not identify gaining access to University with an increase in welfare. Finally, I consider a funding system where only those that send their offspring to university support the funding of higher education.
Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells

Abstract. Objectives: Microgravity is known to affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). However, a few controversial findings have recently been reported with respect to the effects of microgravity on BMSC proliferation. Thus, we investigated the effects of simulated microgravity on rat BMSC (rBMSC) proliferation and their osteogeneic potential. Materials and methods: rBMSCs isolated from marrow using our established effective method, based on erythrocyte lysis, were identified by their surface markers and their proliferation characteristics under normal conditions. Then, they were cultured in a clinostat to simulate microgravity, with or without growth factors, and in osteogenic medium. Subsequently, proliferation and cell cycle parameters were assessed using methylene blue staining and flow cytometry, respectively; gene expression was determined using Western blotting and microarray analysis. Results: Simulated microgravity inhibited population growth of the rBMSCs, cells being arrested in the G0/G1 phase of cell cycle. Growth factors, such as insulin‐like growth factor‐I, epidermal growth factor and basic fibroblastic growth factor, markedly stimulated rBMSC proliferation in normal gravity, but had only a slight effect in simulated microgravity. Akt and extracellular signal‐related kinase 1/2 phosphorylation levels and the expression of core‐binding factor α1 decreased after 3 days of clinorotation culture. Microarray and gene ontology analyses further confirmed that rBMSC proliferation and osteogenesis decreased under simulated microgravity. Conclusions: The above data suggest that simulated microgravity inhibits population growth of rBMSCs and their differentiation towards osteoblasts. These changes may be responsible for some of the physiological changes noted during spaceflight.
Gambling-Related Distortions and Problem Gambling in Adolescents: A Model to Explain Mechanisms and Develop Interventions

Although a number of gambling preventive initiatives have been realized with adolescents, many of them have been developed in absence of a clear and explicitly described theoretical model. The present work was aimed to analyze the adequacy of a model to explain gambling behavior referring to gambling-related cognitive distortions (Study 1), and to verify the effectiveness of a preventive intervention developed on the basis of this model (Study 2). Following dual-process theories on cognitive functioning, in Study 1 we tested a model in which mindware gap, i.e., susceptibility to the gambler’s fallacy, and contaminated mindware, i.e., superstitious thinking, were the antecedents of gambling-related cognitive distortions that, in turn, affect gambling frequency and problem gambling. Participants were 306 male adolescents (Mage = 17.2 years). A path analysis indicated that cognitive distortions have a mediating role in the relationship that links probabilistic reasoning fallacy and superstitious thinking with problem gambling. Following these findings, in Study 2 we developed a school-based intervention aimed to reduce gambling-related cognitive distortions acting on the above cited mindware problems. A pre- and post-test design – with a 6 months follow-up – was performed with 34 male adolescents (Mage = 16.8), randomly assigned to two groups (Training and No Training), and their baseline equivalence was verified. A Mixed 2 × 2 ANOVA attested a significant Time X Group interaction, indicating a significant reduction of the cognitive distortions from pre-test to post-test only in the Training group. The follow-up attested to the stability of the training effects and the reduction of gambling frequency over time. These findings suggest that prevention strategies should address mindware problems, which can be considered as predictors of gambling-related cognitive distortions.
Combined typhoid fever and hepatitis A vaccine: comparison of immunogenicity and safety to concomitant monovalent vaccine over 3 years.

BACKGROUND The safety and immunogenicity of Viatim, a combined hepatitis A (HA) and typhoid fever (Vi) vaccine, were compared with the monovalent component vaccines up to and 1 month after a booster dose at 3 years. METHODS Healthy, adult volunteers were randomized to receive Viatim (group A, n = 179) or separate HA and Vi vaccines (group B, n = 181); subgroups were boosted after 3 years with Viatim (groups C and D, n = 56 and 46, respectively). Local and systemic reactions were recorded for 28 days postvaccination. Seroconversion and seroprotection rates and geometric mean antibody concentrations were measured at 14 and 28 days, 1, 2, and 3 years postvaccination, and 28 days after the booster dose. RESULTS Local and systemic safety profiles were equivalent between the two groups. Immediate local reactions were infrequent (1 in group A and 2 in group B). Local reactions, consisting mostly of mild or moderate pain, were least frequent with monovalent HA. Antibody concentrations to both antigens were similar in groups A and B, in which HA seroprotection rates (> or = 20 mIU/mL) were respectively, 98.7% and 100% at day 28, and 99.1% and 99.0% after 3 years, achieving 100% after the booster. Vi seroprotection rates (> or = 1 microg/mL) of 85.2% and 84.9% after 28 days fell to 32.1% and 35.6% after 3 years, increasing to 67.3% and 69.8% after the booster dose. CONCLUSIONS The combined HA/Vi vaccine, Viatim, had equivalent tolerability and safety and was as rapidly immunogenic as its component monovalent vaccines when given concurrently. A booster dose after 3 years significantly increased antibody levels with some evidence of relative hyporesponsiveness of the typhoid response.
Effects of Gelatin-Based Edible Films Enriched with Laurel Essential Oil on the Quality of Rainbow Trout (Oncorhynchus mykiss) Fillets During Refrigerated Storage

Summary The effects of gelatin films enriched with laurel leaf essential oil on the quality of rainbow trout (Oncorhynchus mykiss) during refrigerated storage at (41) °C were examined over a period of 26 days. Fish fillets were wrapped with 8 % gelatin films containing 0, 0.1 and 1 % (by volume per mass) of laurel essential oil and vacuum packaged. Sensory (raw and cooked fish), microbiological (total viable counts, psychrotrophic bacteria counts, Enterobacteriaceae and lactic acid bacteria) and chemical (proximate composition, pH, total volatile base nitrogen (TVB-N), thiobarbituric acid (TBA), free fatty acid (FFA) and peroxide value (PV)) analysis, and colour measurement were carried out during the storage period and shelf-life was determined periodically. The obtained results showed that the gelatin film enriched with laurel essential oil was suitable for the preservation of rainbow trout fillet and the ability of laurel essential oil to preserve the film depended on its ratio. Combined effects of gelatin film and laurel essential oil (1 % by volume per mass) was efficient in maintaining the quality characteristics at an acceptable level up to 22 days of storage, while the control and gelatin film without the essential oil reached an unacceptable level at 15 and 20 days, respectively.