Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Quantitative and Semiquantitative Dynamic Contrast-Enhanced MRI With Respect to Their Correlation to Delayed Gadolinium-Enhanced MRI of the Cartilage in Patients With Early Rheumatoid Arthritis

Objective The objective of this study was to investigate the correlation between semiquantitative and quantitative dynamic contrast-enhanced (DCE) parameters with delayed gadolinium-enhanced magnetic resonance imaging (MRI) of the cartilage (dGEMRIC). Methods Fifteen patients with early rheumatoid arthritis (RA) from the ArthroMark cohort were investigated at a 3-T MRI scanner. The metacarpophalangeal (MCP) joint of the index finger was examined with DCE-MRI and dGEMRIC. Semiquantitative and quantitative DCE perfusion parameters were calculated. The RA MRI score of the second MCP joint and the joint space width were measured. Results Significant correlations were noted between both semiquantitative and quantitative DCE parameters and the RA MRI score of the second MCP joint. There was a significant negative correlation between DCE parameters and dGEMRIC. No association between joint space width and DCE parameters was observed. Conclusions Semiquantitative and quantitative analyses of perfusion are applicable to show that cartilage damage correlates with the inflammation activity despite the absence of joint space narrowing.
Fototerapia causa danos ao DNA de leucócitos mononucleares periféricos em recém-nascidos a termo

OBJECTIVE: Our aim was to determine whether endogenous mononuclear leukocyte DNA strand is a target of phototherapy. METHODS: The study included 65 term infants aged between 3-10 days that had been exposed to intensive (n = 23) or conventional (n = 23) phototherapy for at least 48 hours due to neonatal jaundice, and a control group (n = 19). DNA damage was assayed by single-cell alkaline gel electrophoresis (comet assay). Plasma total antioxidant capacity and total oxidant status levels were also measured, and correlation between DNA damage and oxidative stress was investigated. RESULTS: Mean values of DNA damage scores in both the intensive and conventional phototherapy groups were significantly higher than those in the control group (p 0.05). There were no significant correlations between DNA damage scores and bilirubin, total oxidant status and oxidative stress levels in either phototherapy group (p > 0.05). CONCLUSIONS: Both conventional phototherapy and intensive phototherapy cause endogenous mononuclear leukocyte DNA damage in jaundiced term infants.
Real versus Artificial Variation in the Thermal Sensitivity of Biological Traits

Whether the thermal sensitivity of an organism’s traits follows the simple Boltzmann-Arrhenius model remains a contentious issue that centers around consideration of its operational temperature range and whether the sensitivity corresponds to one or a few underlying rate-limiting enzymes. Resolving this issue is crucial, because mechanistic models for temperature dependence of traits are required to predict the biological effects of climate change. Here, by combining theory with data on 1,085 thermal responses from a wide range of traits and organisms, we show that substantial variation in thermal sensitivity (activation energy) estimates can arise simply because of variation in the range of measured temperatures. Furthermore, when thermal responses deviate systematically from the Boltzmann-Arrhenius model, variation in measured temperature ranges across studies can bias estimated activation energy distributions toward higher mean, median, variance, and skewness. Remarkably, this bias alone can yield activation energies that encompass the range expected from biochemical reactions (from ∼0.2 to 1.2 eV), making it difficult to establish whether a single activation energy appropriately captures thermal sensitivity. We provide guidelines and a simple equation for partially correcting for such artifacts. Our results have important implications for understanding the mechanistic basis of thermal responses of biological traits and for accurately modeling effects of variation in thermal sensitivity on responses of individuals, populations, and ecological communities to changing climatic temperatures.
Intragenomic Conflict over Soldier Allocation in Polyembryonic Parasitoid Wasps

Understanding the selection pressures that have driven the evolution of sterile insect castes has been the focus of decades of intense scientific debate. An amenable empirical test bed for theory on this topic is provided by the sterile-soldier caste of polyembryonic parasitoid wasps. The function of these soldiers has been a source of controversy, with two basic hypotheses emerging: the “brood-benefit” hypothesis that they provide an overall benefit for their siblings and the “sex-ratio-conflict” hypothesis that the soldiers mediate a conflict between brothers and sisters by killing their opposite-sex siblings. Here, we investigate the divergent sex-ratio optima of a female embryo’s maternal-origin and paternal-origin genes, to determine the potential for, and direction of, intragenomic conflict over soldiering. We then derive contrasting empirically testable predictions concerning the patterns of genomic imprinting that are expected to arise out of this intragenomic conflict, for the brood-benefit versus the sex-ratio-conflict hypothesis of soldier function.
Anemia Screening Using a Compact Hemoglobin Meter

Anemia is a basic disease associated with various serious pathological conditions. Thus, effectively screening or monitoring patients for anemia is a critical issue for the World Health Organization. The recently developed Astrim SU, is a portable, noninvasive monitoring device for hemoglobin. In the present study, we investigated the efficacy and validity of the device for measuring basic items including hemoglobin and screening for anemia. Our data demonstrated the usefulness and applicability of the device in diverse clinical circumstances.
Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength

The development of bone‐rebuilding anabolic agents for treating bone‐related conditions has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation. More recently, administration of sclerostin‐neutralizing monoclonal antibodies in rodent studies has shown that pharmacologic inhibition of sclerostin results in increased bone formation, bone mass, and bone strength. To explore the effects of sclerostin inhibition in primates, we administered a humanized sclerostin‐neutralizing monoclonal antibody (Scl‐AbIV) to gonad‐intact female cynomolgus monkeys. Two once‐monthly subcutaneous injections of Scl‐AbIV were administered at three dose levels (3, 10, and 30 mg/kg), with study termination at 2 months. Scl‐AbIV treatment had clear anabolic effects, with marked dose‐dependent increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. Bone densitometry showed that the increases in bone formation with Scl‐AbIV treatment resulted in significant increases in bone mineral content (BMC) and/or bone mineral density (BMD) at several skeletal sites (ie, femoral neck, radial metaphysis, and tibial metaphysis). These increases, expressed as percent changes from baseline were 11 to 29 percentage points higher than those found in the vehicle‐treated group. Additionally, significant increases in trabecular thickness and bone strength were found at the lumbar vertebrae in the highest‐dose group. Taken together, the marked bone‐building effects achieved in this short‐term monkey study suggest that sclerostin inhibition represents a promising new therapeutic approach for medical conditions where increases in bone formation might be desirable, such as in fracture healing and osteoporosis. © 2010 American Society for Bone and Mineral Research
Adaptive Use of Information during Growth Can Explain Long-Term Effects of Early Life Experiences

Development is a continuous process during which individuals gain information about their environment and adjust their phenotype accordingly. In many natural systems, individuals are particularly sensitive to early life experiences, even in the absence of later constraints on plasticity. Recent models have highlighted how the adaptive use of information can explain age-dependent plasticity. These models assume that information gain and phenotypic adjustments either cannot occur simultaneously or are completely independent. This assumption is not valid in the context of growth, where finding food results both in a size increase and learning about food availability. Here, we describe a simple model of growth to provide proof of principle that long-term effects of early life experiences can arise through the coupled dynamics of information acquisition and phenotypic change in the absence of direct constraints on plasticity. The increase in reproductive value from gaining information and sensitivity of behavior to experiences declines across development. Early life experiences have long-term impacts on age of maturity, yet—due to compensatory changes in behavior—our model predicts no substantial effects on reproductive success. We discuss how the evolution of sensitive windows can be explained by experiences having short-term effects on informational and phenotypic states, which generate long-term effects on life-history decisions.
Necrotizing Enterocolitis: An Update on the Benefits of Breast Milk

Necrotizing enterocolitis (NEC) is the leading cause of death for preterm infants resulting from gastrointestinal disease. This review will focus on several components of human breast milk that may be beneficial in the prevention and treatment of NEC. The severe pathological features of NEC include inflammation, mucosal ulceration and disruption of the intestinal barrier. Despite maximal neonatal intensive care, the incidence and mortality rate of the disease remains high. Administration of breast milk, as well as donor breast milk, to preterm infants has been shown to reduce the incidence of NEC. Beyond this, there is no disease specific treatment for NEC. The immunomodulatory and protective properties of human breast milk have been evaluated in search of key components that may be utilized for the effective prevention and treatment of NEC.
BMD screening in older women: Initial measurement and testing interval

Screening is the early diagnosis of presymptomatic disease among well individuals in the general population. (1) The purpose of osteoporosis screening using bone mineral density (BMD) testing by dual energy X-ray absorptiometry (DXA) is to identify a presymptomatic condition (osteoporosis as defined by World Health Organization diagnostic criteria) that can be treated to prevent an adverse clinical outcome (fragility fractures). An osteoporosis screening program primarily targets the prevention of hip and clinical vertebral fractures because these fractures are associated with the majority of morbidity and health care utilization attributable to osteoporotic fractures. The U.S. Preventive Services Task Force(2) (USPSTF) assigned osteoporosis screening an evidence grade B based on findings from prospective cohort studies of DXA testing and results of randomized controlled trials (RCTs) demonstrating that pharmacologic therapy in postmenopausal women with osteoporosis(3–6) reduced the incidence of fractures. Until recently, prospective data regarding an osteoporosis screening interval were lacking,(7) and several organizations(8–13) recommended BMD screening intervals of about 2 to 5 years based on expert opinion.
An International Physician Survey of Pulmonary Arterial Hypertension Management

We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients' New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH.
Assessment of sotalol prescribing in a community hospital: opportunities for clinical pharmacist involvement

Objective Due to risk of serious adverse drug events (ADEs) sotalol use is limited in renal insufficiency and heart failure. To reduce potential life‐threatening ADEs, medication safety initiatives that ensure appropriate dosing of sotalol are necessary. Pharmacist‐managed renal dosing assessment programmes ensure appropriate dosing of renally eliminated medications. A prospective medication safety evaluation was conducted to assess the need to include sotalol in an existing renal dosing assessment programme as well as the impact of clinical pharmacist assessment on sotalol prescribing.
A multinational study to develop universal standardization of whole‐body bone density and composition using GE Healthcare Lunar and Hologic DXA systems

Dual‐energy x‐ray absorptiometry (DXA) is used to assess bone mineral density (BMD) and body composition, but measurements vary among instruments from different manufacturers. We sought to develop cross‐calibration equations for whole‐body bone density and composition derived using GE Healthcare Lunar and Hologic DXA systems.
Absence of beta-amyloid in cortical cataracts of donors with and without Alzheimer's disease

Purpose Eye lenses from human donors with and without Alzheimer's disease (AD) were studied to evaluate the presence of amyloid in cortical cataract. Methods We obtained 39 lenses from 21 postmortem donors with AD and 15 lenses from age-matched controls. For 17 donors, AD was clinically diagnosed by general physicians and for 4 donors the AD diagnosis was neuropathologically confirmed. As controls, 7 donors with pronounced cortical opacities and 8 donors with almost transparent lenses were selected. All lenses were photographed in a dark field stereomicroscope. Histological sections were analyzed using a standard and a more sensitive Congo red protocol, thioflavin staining and beta-amyloid immunohistochemistry. Results Of the 21 donors with AD, 6 had pronounced bilateral cortical lens opacities and 15 only minor or no cortical opacities. Thioflavin, standard and modified Congo red staining were positive in the control brain tissues and in the dystrophic cornea. Beta-amyloid immunohistochemistry was positive in the brain tissues but not in the cornea sample. Lenses from control and AD donors were, without exception, negative after Congo red, thioflavin, and beta-amyloid immunohistochemical staining. Conclusion The absence of staining in AD and control lenses with the techniques employed lead us to conclude that there is no beta-amyloid in lenses from donors with AD or in control cortical cataracts.
PPARγ attenuates hypoxia-induced hypertrophic transcriptional pathways in the heart

Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms. C57BL/6J mice were exposed to normoxia (21% O2) or hypoxia (10% O2) for 21 days. During the final 10 days of exposure, selected mice were treated with the PPARγ ligand, pioglitazone. RV systolic pressure (RVSP) and RVH were measured, and NFATc2 and NF-kB/p65 protein levels were measured in RV and LV nuclear and cytosolic fractions. Cardiomyocyte hypertrophy was assessed with wheatgerm agglutinin staining. NFAT activation was also examined with luciferase reporter mice and analysis of protein levels of selected transcriptional targets. Chronic-hypoxia increased: (1) RVH, RVSP, and RV cardiomyocyte hypertrophy; (2) NFATc2 and NF-κB activation in RV nuclear homogenates; (3) RV and LV NFAT luciferase activity; and (4) RV protein levels of brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MyHC). Treatment with pioglitazone attenuated hypoxia-induced increases in both RV and LV NFAT luciferase activity. Chronic hypoxia caused sustained RV NFATc2 and NF-κB activation. Pioglitazone attenuated PH, RVH, cardiomyocyte hypertrophy, and activation of RV hypertrophic signaling and also attenuated LV NFAT activation. PPARγ favorably modulates signaling derangements in the heart as well as in the pulmonary vascular wall.
Odanacatib in the treatment of postmenopausal women with low bone mineral density: Five years of continued therapy in a phase 2 study

Odanacatib (ODN) is a selective inhibitor of the collagenase cathepsin K that is highly expressed by osteoclasts. In this 2‐year, phase 2, dose‐ranging trial, postmenopausal women with bone mineral density (BMD) T‐scores −2.0 to −3.5 at spine or hip were randomized to weekly placebo or ODN 3, 10, 25, or 50 mg plus vitamin D3 and calcium. Prespecified trial‐extensions continued through 5 years. In year 3, all women were re‐randomized to ODN 50 mg or placebo. For years 4 and 5, women who received placebo or ODN 3 mg in years 1 and 2 and placebo in year 3 received ODN 50 mg; others continued year 3 treatments. Endpoints included lumbar spine (primary), hip, 1/3 radius, and total body BMD; markers of bone metabolism; and safety. Women in the year 4 to 5 extension receiving placebo (n = 41) or ODN 50 mg (n = 100) had similar baseline characteristics. For women who received ODN (10–50 mg) for 5 years, spine and hip BMD increased over time. With ODN 50 mg continually for 5 years (n = 13), mean lumbar spine BMD percent change from baseline (95% confidence interval [CI]) was 11.9% (7.2% to 16.5%) versus −0.4% (−3.1% to 2.3%) for women who were switched from ODN 50 mg to placebo after 2 years (n = 14). In pooled results of women receiving continuous ODN (10–50 mg, n = 26–29), year 5 geometric mean percent changes from baseline in bone resorption markers cross‐linked N‐telopeptide of type I collagen (NTX)/creatinine and cross‐linked C‐telopeptide (CTX) were approximately −55%, but near baseline for bone formation markers bone‐specific alkaline phosphatase (BSAP) and amino‐terminal propeptide of type I procollagen (P1NP). In women switched from ODN 10 to 50 mg to placebo after 2 years (n = 25), bone turnover markers were near baseline. In summary, women receiving combinations of ODN (10–50 mg) for 5 years had gains in spine and hip BMD and showed larger reductions in bone resorption than bone formation markers. Discontinuation of ODN resulted in reversal of treatment effects. Treatment with ODN for up to 5 years was generally well‐tolerated. © 2012 American Society for Bone and Mineral Research.
The influence of evidence‐based medicine training on decision‐making in relation to over‐the‐counter medicines: a qualitative study

To explore the role of evidence of effectiveness when making decisions about over‐the‐counter (OTC) medication and to ascertain whether evidence‐based medicine training raised awareness in decision‐making. Additionally, this work aimed to complement the findings of a previous study because all participants in this current study had received training in evidence‐based medicine (unlike the previous participants).
Paxillin contracts the osteoclast cytoskeleton

Osteoclastic bone resorption depends upon the cell's ability to organize its cytoskeleton via the αvβ3 integrin and osteoclastogenic cytokines. Because paxillin associates with αvβ3, we asked if it participates in skeletal degradation. Unlike deletion of other αvβ3‐associated cytoskeleton‐regulating molecules, which impairs the cell's ability to spread, paxillin‐deficient (Pax−/−) osteoclasts, generated from embryonic stem cells, “superspread” in response to receptor activator of NF‐κB ligand (RANKL) and form large, albeit dynamically atypical, actin bands. Despite their increased size, Pax−/− osteoclasts resorb bone poorly, excavating pits approximately one‐third normal depth. Ligand‐occupied αvβ3 or RANKL promotes paxillin serine and tyrosine phosphorylation, the latter via cellular sarcoma (c‐Src). The abnormal Pax−/− phenotype is rescued by wild‐type (WT) paxillin but not that lacking its LD4 domain. In keeping with the appearance of mutant osteoclasts, WT paxillin, overexpressed in WT cells, contracts the cytoskeleton. Most importantly, the abnormal phenotype of Pax−/− osteoclasts likely represents failed RANKL‐mediated delivery of myosin IIA to the actin cytoskeleton via the paxillin LD4 domain but is independent of tyrosine phosphorylation. Thus, in response to RANKL, paxillin associates with myosin IIA to contract the osteoclast cytoskeleton, thereby promoting its bone‐degrading capacity. © 2012 American Society for Bone and Mineral Research.
Age‐related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: A population‐based HR‐pQCT study

In this cross‐sectional study, we aimed to predict age‐related changes in bone microarchitecture and strength at the distal radius (DR) and distal tibia (DT) in 644 Canadian adults (n = 442 women and 202 men) aged 20 to 99 years. We performed a standard morphologic analysis of the DR and DT with high‐resolution peripheral quantitative computed tomography (pQCT) and used finite‐element analysis (FEA) to estimate bone strength (failure load) and the load distribution. We also calculated a DR load‐to‐strength ratio as an estimate of forearm fracture risk. Total bone area, which was 33% larger in young men at both sites, changed similarly with age in women and men at the DT but increased 17% more in men than in women at the DR (p < .001). Trabecular number and thickness (Tb.Th) were 7% to 20% higher in young men than in young women at both sites, and with the exception of Tb.Th at the DR, which declined more with age in men (−16%) than in women (−2%, p < .01), the age‐related decline in these outcomes was similar in women and in men. In the cortex, porosity (Ct.Po) was 31% to 44% lower in young women than in young men but increased 92% to 176% more with age in women than in men (p < .001). The DR cortex carried 14% more load in young women than in young men, and the percentage of load carried by the DR cortex did not change with age in women but declined by 17% in men (p < .01). FEA‐estimated bone strength was 34% to 47% greater in young men, but the predicted change with age was similar in both sexes. In contrast, the load‐to‐strength ratio increased 27% more in women than in men with age (p < .01). These results highlight important site‐ and sex‐specific differences in patterns of age‐related bone loss. In particular, the trends for less periosteal expansion, more porous cortices, and a greater percentage of load carried by the DR cortex in women may underpin sex differences in forearm fracture risk. © 2011 American Society for Bone and Mineral Research.