Miracle-dz/UniFAR-FTUs huggingface dataset:
Psoriasis and systemic inflammation: underdiagnosed enthesopathy

Our understanding of the pathogenesis of psoriasis is changing rapidly and the traditional view that it is a disease limited to the skin continues to be challenged. Indeed, there is convincing evidence that psoriasis patients have a higher prevalence of comorbid disease, particularly cardio‐metabolic disorders and psoriatic arthritis (PsA). The results of recent investigations into psoriasis and cardiovascular or metabolic comorbidities provide increasing evidence for a possible shared pathogenic mechanism for these disorders, linked by an underlying chronic systemic inflammatory state. This highlights the importance of investigating associated comorbidities beyond skin manifestations. Psoriatic arthritis is a chronic inflammatory arthropathy that can occur in association with psoriasis and most commonly affects the distal joints in the hands and feet. Skin lesions precede arthritic symptoms in approximately 75% of cases; typically, the cutaneous manifestations of the disease develop 10 years prior to the onset of joint symptoms. This disease course, therefore, provides a potential window of opportunity to initiate effective and aggressive therapies to prevent long‐term damage, if symptoms of PsA can be detected early. One of the major features of PsA is enthesitis, yet clinically asymptomatic cases of entheseal abnormalities are likely to go undiagnosed. This concept was evaluated in a prospective study in which entheseal changes in clinically asymptomatic psoriasis patients were compared with findings from a control group. Ultrasonography detected a significantly higher incidence of entheseal abnormalities in patients with psoriasis, despite the absence of clinical symptoms of arthropathy. Ongoing monitoring of these patients has also revealed that a higher baseline score for enthesitis may be associated with a more severe psoriasis outcome. These findings demonstrate that detecting early signs of PsA in asymptomatic patients with psoriasis may have the potential to positively influence disease prognosis and ultimately clinical outcome. Dermatologists can, therefore, play a key role in the early detection and management of PsA.
A sympathetic nervous system evaluation of obesity stigma

The portrayal of obesity in the media is often one of negativity. Consequently, it may generate an increase in stigma. Obesity stigma, a form of social discrimination, is responsible for many of the negative psychological and physiological effects on individual wellness. These effects not only impact individual health, but also affect the economy, and ultimately, societal wellness. In an attempt to examine the influence of the media on obesity stigma, this study tested the hypothesis that positive priming would lead to a reduction in obesity stigma. To further our understanding of this relationship, we: 1) examined the role of priming on physiological measures (e.g. salivary alpha amylase and skin conductance) in 70 college students by introducing positive and negative media images of individuals with obesity, and 2) assessed psychological measures (e.g. perceived stress, need to belong, and self-esteem, and Body Mass Index). After the priming manipulation, participants read a vignette depicting the discrimination of an individual with obesity and answered subsequent questions assessing participants’ attributional blame of obesity. Results of this study revealed that priming affects physiological responding to obesity stigmatization. In conclusion, these findings suggest that incorporating positive media images of individuals with obesity may be an effective tool for reducing stigma and the various physiological consequences associated with it, which in turn, can enhance societal health and wellness.
Calf ligated intestinal segment test to detect enterotoxigenic Escherichia coli

The ligated intestinal segment test in the young calf was utilized to establish the enterotoxigenicity of approximately 600 Escherichia coli isolates obtained from fecal specimens intestinal contents of calves with diarrheal disease. One hundred and fifty isolates were routinely tested in a single calf. There was little problem with false-positive reactions. False-negative reactions normally occurred only if the isolate was tested in the posterior 3 m of the small intestine. The ligated small intestine of the calf was distended by E. coli isolates of bovine, porcine, and human origin. Use of the calf ligated intestinal segment test is recommended to determine the enterotoxigenicity of E. coli isolates of bovine origin.
Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: Prevalence, clinical correlates, and prognostic relevance

SRSF2, SF3B1, and U2AF35 (U2AF1) are the three most frequent genes involved with spliceosome mutations in myeloid malignancies. SF3B1 mutations are most frequent (~80%) in myelodysplastic syndromes (MDS) with ring sideroblasts (RS) but lack prognostic relevance. SRSF2 mutations are associated with shortened overall (OS) and leukemia‐free survival (LFS) in both MDS and myelofibrosis. In this study of 226 patients with chronic myelomonocytic leukemia (CMML), mutational frequencies were 40% for SRSF2 (all affecting P95), 6% for SF3B1 (primarily K700E) and 9% for U2AF35 (mostly S34F and Q157P/R). These mutations were mutually exclusive and 54% of the patients displayed at least one mutation. The three mutation groups were phenotypically similar, with the exception of higher RS% (P < 0.0001) in patients with SF3B1 mutations. At a median follow‐up of 15 months, 176 (78%) deaths and 32 (14%) leukemic transformations were documented. OS (median survivals of 17, 16, 17, and 20 months; P = 0.48) and LFS (leukemic transformation rates of 17, 13, 15, and 5%; P = 0.63) were similar among patients with none of the three mutations, SRSF2, SF3B1, or U2AF35 mutations, respectively. We conclude that SRSF2 is the most frequently mutated spliceosome gene in CMML but neither it nor SF3B1 or U2AF35 mutations are prognostically relevant. Am. J. Hematol. 88:201–206, 2013. © 2012 Wiley Periodicals, Inc.
Effects of a dietary intervention and weight change on vasomotor symptoms in the Women’s Health Initiative

Objective The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women. Methods We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women’s Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations. Results In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (≥10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS. Conclusions Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.
Composition and Activity of the Board of Directors: Impact on ESG Performance in the Banking System

A growing body of research suggests that the composition of a firm’s board of directors can influence its environmental, social and governance (ESG) performance. In the banking industry, ESG performance has not yet been explored to discover how a critical mass of women on the board of directors affects performance. This paper seeks to fill this gap in the literature by testing the impact of a critical mass of female directors on ESG performance. Other board characteristics are accounted for: independence, size, frequency of meetings and Corporate Social Responsibility (CSR) sustainability committee. We use fixed effects panel regression models on a sample of 108 listed banks in Europe and the United States for the period 2011–2016. Our main empirical evidence shows that the relationship between women on the board of directors and a bank’s ESG performance is an inverted U-shape. Therefore, the critical mass theory for banks is not supported, confirming that only gender-balanced boards positively impact a bank’s performance for sustainability. There is a positive link between ESG performance and board size or the presence of a CSR sustainability committee, while it is negative with the share of independent directors. With this work, we stress the key role of corporate governance principles in banks’ ESG performance, with relevant implications for both banks and supervisory authorities.
New approaches to assess the transthyretin binding capacity of bioactivated thyroid hormone disruptors.

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl-ethers (PBDEs) are metabolized into hydroxylated metabolites (OH-PCBs/PBDEs), which can disrupt the thyroid hormone homeostasis. Binding of these metabolites to transport proteins such as transthyretin (TTR) is an important mechanism of their toxicity. Several methods to quantify the competitive thyroxine (T(4)) displacement potency of pure metabolites exist. However, quantification of the potency of in vitro metabolized PCBs and PBDEs has drawbacks related to the coextraction of compounds disturbing the T(4)-TTR competitive binding assay. This study identifies and quantifies the major coextractants namely cholesterol, saturated and nonsaturated fatty acids (SFA and NSFA) at levels above 20 nmol per mg equivalent protein following various extraction methods. Their TTR binding potency was analyzed in a downscaled, nonradioactive fluorescence displacement assay. At concentration factors needed for TTR competitive binding, at least 10μM of these coextracts is present, whereas individual SFA and NSFA disturb the assay from 0. 3μM. The effectiveness of the in vitro metabolism and extraction of the model compounds CB 77 and BDE 47 was chemically quantified with a newly developed chromatographic method analyzing silylated derivatives of the OH-metabolites and coextractants. A new method to selectively extract metabolites and limit coextraction of disturbing compounds to less than 5 nmol per mg equivalent protein is presented. It is now possible to make a dose-response curve up to 50% inhibition with bioactivated CB 77 and BDE 47. The toxic potencies of bioactivated persistent organic pollutants (POPs) should be taken into account to prevent serious underestimation of their hazard and risk.
Bile Acid Malabsorption in Inflammatory Bowel Disease

Abstract:Bile acid malabsorption (BAM) is a common but an underestimated and often neglected sign of inflammatory bowel diseases (IBDs), especially those affecting the distal ileum. Clinically relevant BAM is most often present in patients with Crohn's ileitis and particularly in ileal-resected Crohn's disease patients. However, deterioration of bile acid (BA) metabolism occurs also in patients with IBD without ileal disease or in those in clinical remission, and the role of BAM in these patients is not well appreciated by clinicians. In a majority of cases, BAM in IBD is caused by impaired conjugated BA reabsorption, mediated by apical sodium/BA cotransporting polypeptide, localized at the luminal surface of the ileal enterocytes. As a consequence, numerous pathological sequelae may occur, including the malfunction of lipid digestion with clinical steatorrhea, impaired intestinal motility, and/or significant changes in the intestinal microflora environment. In this review, a detailed description of the pathophysiological mechanisms of BAM-related diarrhea is presented. Although BAM is present in a significant number of patients with Crohn's disease, its laboratory assessment is not routinely included in diagnostic workups, partially because of costs, logistical reasons, or the unavailability of the more sophisticated laboratory equipment needed. Simultaneously, novel findings related to the effects of the BA signaling pathways on immune functions (mediated through TGR5, cell membrane G protein-coupled BA receptor 1, nuclear farnesoid X receptor, nuclear pregnane X receptor, or nuclear vitamin D receptor) are discussed along with intestinal metabolism in its relationship to the pathogenesis of IBD.
Isolated talonavicular arthrodesis for talonavicular arthritis: a follow-up study.

We have reviewed a single surgeon's (M.S.) experience of talonavicular arthrodesis in 7 feet in 7 patients with isolated talonavicular arthritis. A standard dorsomedial approach was used to the talonavicular joint. Fixation was performed with 5.5-mm, partially threaded, cancellous screws. The visual analog scale for the foot and ankle (VASFA) was used to measure the preoperative and postoperative results in the categories of pain, function, other complaints, and total score. The follow-up period was 17 to 90 months (mean 48). The overall VASFA score ranged from +19.2 to +57.6 (mean +33.2, p < .01). The VASFA score for pain ranged from +19 to +74.8 (mean +51.3, p < .01). The VASFA score for function ranged from +12.5 to +68.2 (mean +28.3, p < .01). The VASFA score for other problems ranged from +12 to +45.8 (mean +25.5, p < .01). None of the 7 feet required revision, and all 7 patients were satisfied with the outcome and would have the operation again. We have concluded that, taking into account the small power of the present study, talonavicular arthrodesis is a successful treatment for isolated talonavicular arthritis.
Solution structure of hypothetical nudix hydrolase DR0079 from extremely radiation‐resistant Deinococcus radiodurans bacterium

Using nuclear magnetic resonance (NMR) based methods, including residual dipolar coupling restraints, we have determined the solution structure of the hypothetical Deinococcus radiodurans Nudix protein DR0079 (171 residues, MW = 19.3 kDa). The protein contains eight β‐strands and three α‐helices organized into three subdomains: an N‐terminal β‐sheet (1–34), a central Nudix core (35–140), and a C‐terminal helix‐turn‐helix (141–171). The Nudix core and the C‐terminal helix‐turn‐helix form the fundamental fold common to the Nudix family, a large mixed β‐sheet sandwiched between α‐helices. The residues that compose the signature Nudix sequence, GX5EX7REUXEEXGU (where U = I, L, or V and X = any amino acid), are contained in a turn‐helix‐turn motif on the face of the mixed β‐sheet. Chemical shift mapping experiments suggest that DR0079 binds Mg2+. Experiments designed to determine the biological function of the protein indicate that it is not a type I isopentenyl‐diphosphate δ‐isomerase and that it does not bind α,β‐methyleneadenosine 5′‐triphosphate (AMPCPP) or guanosine 5′‐[β,γ‐imido]triphosphate (GMPPNP). In this article, the structure of DR0079 is compared to other known Nudix protein structures, a potential substrate‐binding surface is proposed, and its possible biological function is discussed. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Who governs? The disputed effects of regionalism on legislative career orientation in multilevel systems

Abstract In multilevel systems, patterns of regional and national political careers reflect processes of regionalisation and federalisation. Yet the effects of regionalism on the orientation of legislative careers remain disputed. Such disputes result from the choice of the unit of analysis, the scarcity of comparative research across countries and over time, and bias in case selection. This article offers a systematic intranational comparative analysis of ‘sister regions’ in four countries that are examples of weak and strong regionalism. It tests the regionalism hypothesis based on an original comparative dataset of 4662 regional and national political careers in Belgium, Canada, Spain, and the UK. The results demonstrate that regionalism matters: regional legislative elites emerge more clearly in polities in which regionalism is stronger. The regionalism hypothesis is particularly supported in Spain and Canada, which have a longer history of regional institutions, but that trend is also confirmed in the UK and Belgium.
Functional influence on sutural growth. A morphometric study in the anterior facial skeleton of the growing rat.

The aim of this study was to quantify the sutural response in the various parts of the rat's upper frontal viscerocranium and study the possible effects caused by reduced masticatory muscle function. Twenty growing male albino rats were randomly divided into two equal groups: one group (Hard Diet group) received the ordinary diet in a hard pellets form, while the other (Soft Diet group) a soft diet. The experimental period started just before the rats' pubertal growth spurt (28 days old) and its duration was 28 days. After death, the heads of the animals were taken for preparation of undecalcified frontal sections, 100 microns thick. Contact microradiographs of six representative homologous sections, for every animal in both groups, were prepared. The mean width, length, height, and interdigitation ratio of the internasal, naso-premaxillary, and interpremaxillary sutures, as well as the orientation of the bony surfaces of the naso-premaxillary suture were quantified on the contact microradiographs using the IBAS automatic image analysis system. The width of the sutural space was found to be significantly greater in the Hard Diet group than in the Soft Diet group in all the sutures studied (P < 0.01). No differences in the interdigitation of the sutures were found between the two groups, except in the internasal suture in the middle part of the snout, where the Hard Diet group exhibited increased interdigitations. The bony surfaces of the naso-premaxillary suture were significantly more parallelly-orientated in the animals with reduced masticatory muscle function (P < 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)
Rates of decline distinguish Alzheimer's disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function.

AIMS Increasing age is the strongest risk factor for Alzheimer's disease (AD). Yet, departure from normal age-related decline for established markers of AD including memory, cognitive decline and brain function deficits, has not been quantified. METHODS We examined the cross-sectional estimates of the "rate of decline" in cognitive performance and psychophysiological measures of brain function over age in AD, preclinical (subjective memory complaint-SMC, Mild Cognitive Impairment-MCI) and healthy groups. Correlations between memory performance and indices of brain function were also conducted. RESULTS The rate of cognitive decline increased between groups: AD showed advanced decline, and SMC/MCI groups represented intermediate stages of decline relative to normal aging expectations. In AD, advanced EEG alterations (excessive slow-wave/reduced fast-wave EEG, decreased working memory P450 component) were observed over age, which were coupled with memory decline. By contrast, MCI group showed less severe cognitive changes but specific decreases in the working memory N300 component and slow-wave (delta) EEG, associated with decline in memory. DISCUSSION AND INTEGRATIVE SIGNIFICANCE: While the cognitive data suggests a continuum of deterioration associated with increasing symptom severity across groups, integration with brain function measures points to possible distinct compensatory strategies in MCI and AD groups. An integrative approach offers the potential for objective markers of the critical turning point, with age as a potential factor, from mild memory problems to disease.
Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease

Age‐related macular degeneration (AMD), a blinding disorder that compromises central vision, is characterized by the accumulation of extracellular deposits, termed drusen, between the retinal pigmented epithelium and the choroid. Recent studies in this laboratory revealed that vitronectin is a major component of drusen. Because vitronectin is also a constituent of abnormal deposits associated with a variety of diseases, drusen from human donor eyes were examined for compositional similarities with other extracellular disease deposits. Thirty‐four antibodies to 29 different proteins or protein complexes were tested for immunoreactivity with hard and soft drusen phenotypes. These analyses provide a partial profile of the molecular composition of drusen. Serum amyloid P component, apolipoprotein E, immunoglobulin light chains, Factor X, and complement proteins (C5 and C5b‐9 complex) were identified in all drusen phenotypes. Transcripts encoding some of these molecules were also found to be synthesized by the retina, retinal pigmented epithelium, and/or choroid. The compositional similarity between drusen and other disease deposits may be significant in view of the recently established correlation between AMD and atherosclerosis. This study suggests that similar pathways may be involved in the etiologies of AMD and other age‐related diseases. —Mullins, R. F. , Russell, S. R. , Anderson, D. H. , Hageman, G. S. Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 14, 835–846 (2000)
A Retroviral-Derived Immunosuppressive Peptide Activates Mitogen-Activated Protein Kinases1

The highly conserved region within the retroviral transmembrane envelope proteins has been implicated in a number of retrovirus-associated mechanisms of immunosuppression. CKS-17, a synthetic peptide representing the prototypic sequence of the immunosuppressive domain, has been found to suppress numerous immune functions, disregulate cytokines, and elevate intracellular cAMP. In this report we show that using a human monocytic cell line THP-1, CKS-17 activates mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase 1 and 2 (ERK1/2). Kinetic studies show that CKS-17 induces an acute increase of ERK1/2 activity followed by a rapid decrease and then a second sustained increase of ERK1/2. CKS-17 also activates MAP kinase/ERK kinase (MEK) with a similar induction pattern. Mutant THP-1 cells isolated in our laboratory, in which CKS-17 exclusively fails to activate cAMP, did not show the transient decrease of CKS-17-induced ERK1/2 phosphorylation. Pretreatment of THP-1 cells or mutant THP-1 cells with cAMP analog or forskolin followed by treatment with CKS-17 showed no activation of MEK or ERK1/2. These results indicate that CKS-17 activates the MEK/ERK cascade and that there is a cross-talk between CKS-17-mediated MEK/ERK cascade and cAMP in that the MEK/ERK cascade is negatively regulated by cAMP. These data present a novel molecular mechanism(s) by this highly conserved retroviral immunosuppressive component.