Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of neutrophil death resembling neither apoptosis nor necrosis by ONO‐AE‐248, a selective agonist for PGE2 receptor subtype 3

An increase of intracellular cAMP mediated by prostaglandin E2 (PGE2) has been shown to delay spontaneous apoptosis of neutrophils. It has been demonstrated that a selective agonist for PGE2 receptor subtype 3 (the EP3 receptor) is capable of decreasing cAMP and stimulating phosphoinositide turnover in various types of cells. We investigated the effect of a selective EP3 receptor agonist, ONO‐AE‐248, on neutrophil viability. ONO‐AE‐248 rapidly caused a unique form of neutrophil death. The agonist primarily induced morphological changes of the nucleus, including fusion of the lobules, decreased compactness of the chromatin, and blebbing and rupture of the nuclear membrane. This was followed by an increase of plasma membrane permeability and cell lysis. During these processes, neither apoptotic changes such as nuclear condensation, DNA fragmentation, and expression of phospholipid phosphatidylserine on the plasma membrane nor necrotic changes such as chromatin clumping and organelle destruction were apparent in the treated neutrophils. The fatal effect of the agonist might be specific for neutrophils because it failed to promote the rapid death of other types of cells. Although activation of neutrophils by ONO‐AE‐248 was not evident, experiments using metabolic inhibitors demonstrated that the agonist caused neutrophil death via the activation of protein kinase C in the presence of intracellular ATP. These findings indicated that EP3 receptor‐mediated signals might promote a novel form of neutrophil death, which differs from typical apoptosis or necrosis.
Evaluation of gallbladder motility in patients with irritable bowel syndrome.

BACKGROUND Abnormalities involving smooth muscle function in different systems of the body have been reported in irritable bowel syndrome (IBS). There are a few studies on gallbladder function in this disorder with conflicting results. OBJECTIVES To investigate the motility of gallbladder in patients with IBS. PATIENTS AND METHODS Forty-eight patients (15 male and 33 female) with IBS and 48 healthy volunteers (15 male and 33 female) were included into the study. Thirty-four patients (70.8%) had constipation predominant and 14 patients (29.2%) had diarrhoea predominant type of IBS. Fasting and postprandial gallbladder volumes were studied using real time ultrasonography and ejection fraction (EF) of gallbladder was calculated. RESULTS While fasting gallbladder volume (FGV) was similar between IBS and control groups (18.0 +/- 4.0 ml vs. 17.8 +/- 4.9 ml, p >0.05), postprandial gallbladder volume (PGV) was lower in IBS group than in the control group (5.5 +/- 1.4 ml vs. 6.2 +/- 1.9 ml, p = 0.03). Accordingly, the mean EF of gallbladders was found to be higher in IBS group than in the control group (69.1% vs. 64.1%, p = 0.0001). There were no difference in FGV, PGV and EF of gallbladders between constipation predominant and diarrhoea predominant IBS patients (p >0.05). CONCLUSION The results of this study indicated that IBS patients have increased emptying of gallbladder compared to healthy subjects.
Comparative model building of interleukin‐7 using interleukin‐4 as a template: A structural hypothesis that displays atypical surface chemistry in helix D important for receptor activation

Using a combination of theoretical sequence structure recognition predictions and experimental disulfide bond assignments, a three‐dimensional (3D) model of human interleukin‐7 (hIL‐7) was constructed that predicts atypical surface chemistry in helix D that is important for receptor activation. A 3D model of hIL‐7 was built using the X‐ray crystal structure of interleukin‐4 (IL‐4) as a template (Walter MR et al., 1992, J Mol Biol. 224: 1075‐1085; Walter MR et al., 1992, J Biol Chem 267:20371–20376). Core secondary structures were constructed from sequences of hIL‐7 predicted to form helices. The model was constructed by superimposing IL‐7 helices onto the IL‐4 template and connecting them together in an up‐up down‐down topology. The model was finished by incorporating the disulfide bond assignments (Cys3, Cys142), (Cys35, Cys130), and (Cys48, Cys93), which were determined by MALDI mass spectroscopy and site‐directed mutagenesis (Cosenza L, Sweeney E, Murphy JR, 1997, J Biol Chem 272:32995–33000). Quality analysis of the hIL‐7 model identified poor structural features in the carboxyl terminus that, when further studied using hydrophobic moment analysis, detected an atypical structural property in helix D, which contains Cys130 and Cys142. This analysis demonstrated that helix D had a hydrophobic surface exposed to bulk solvent that accounted for the poor quality of the model, but was suggestive of a region in IL‐7 that may be important for protein interactions. Alanine (Ala) substitution scanning mutagenesis was performed to test if the predicted atypical surface chemistry of helix D in the hIL‐7 model is important for receptor activation. This analysis resulted in the construction, purification, and characterization of four hIL‐7 variants, hIL‐7 (K121A), hIL‐7(L136A), hIL‐7(K140A), and hIL‐7(W143A), that displayed reduced or abrogated ability to stimulate a murine IL‐7 dependent pre‐B cell proliferation. The mutant hIL‐7(W143A), which is biologically inactive and displaces [125I]‐hIL‐7, is the first reported IL‐7R system antagonist.
Arterial Chemotherapy and Conformal Radiation Abolish Malignant Biliary Obstruction

Malignant biliary obstruction has been a challenge to clinical practitioners, especially when it is serious and complete. Chemotherapy or radiation alone is often unsuccessful. In this study, the authors report a 59-year-old patient with complete common bile duct obstruction caused by cholangiocarcinoma who was treated with arterial chemotherapy followed by 3-dimensional conformal radiation, which resulted in a good clinical outcome.
Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine.

OBJECTIVE Treatment-resistant schizophrenia poses a major therapeutic challenge. This multicenter, double-blind, randomized study compared the efficacy and safety of aripiprazole and perphenazine in treatment-resistant patients with schizophrenia. METHOD Schizophrenia patients (DSM-IV diagnosis) with a history of antipsychotic resistance underwent 4 to 6 weeks of open-label treatment with olanzapine or risperidone to confirm treatment resistance. Only patients who completed this open-label period and failed to respond (< 20% improvement in Positive and Negative Syndrome Scale [PANSS] total score or a Clinical Global Impressions-Severity of Illness score >or= 4) entered the 6-week, double-blind treatment phase. In all, 300 patients with confirmed treatment resistance were randomly assigned to aripiprazole (15-30 mg/day) or perphenazine (8-64 mg/day). The primary outcome measure was change in PANSS score from baseline. The study was conducted between August 30, 2000, and March 18, 2002. RESULTS Both aripiprazole and perphenazine treatment were associated with clinically relevant improvements in PANSS total scores from baseline. After 6 weeks, 27% of aripiprazole-treated patients and 25% of perphenazine-treated patients were responders (>or= 30% decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2). Perphenazine-treated patients had a higher incidence of extrapyramidal symptom-related adverse events, mean increases (i.e., worsening) in extrapyramidal symptom rating scale scores, and a higher rate of elevated prolactin levels than aripiprazole (57.7% vs. 4.4%, p < .001). Improvements in quality of life considered to be clinically relevant (>or= 20% improvement in Quality of Life Scale score) occurred in 36% of the aripiprazole-treated patients and in 21% of those treated with perphenazine (p = .052). CONCLUSIONS Aripiprazole and perphenazine, at the doses used here, can improve the symptoms of schizophrenia in treatment-resistant patients who have failed to respond to olanzapine or risperidone.
Less than Adequate Vitamin D Status and Intake in Latin America and the Caribbean: A Problem of Unknown Magnitude

Background The prevalence of vitamin D deficiency in Latin America and the Caribbean is unknown. Objective To examine the prevalence data available on vitamin D deficiency in Latin America and the Caribbean. Methods A systematic review was conducted in 2011. Studies using biochemical biomarkers and dietary intake estimation were included. Studies conducted in apparently healthy individuals, independently of age, latitude, skin pigmentation, and season of the year at the time of blood collection, were included. Results A total of 243 studies were identified. The final number of selected studies was 28, including two National Health Surveys (Mexico and Argentina). There are studies that report the vitamin D status of specific subgroups conducted in Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, and Mexico. However, the small sample sizes in these studies and thus the low national representativeness of the reported data do not allow for an accurate assessment of vitamin D status at the regional level. In the majority of the countries with available data, we observed that vitamin D insufficiency was classified as a mild, moderate, or severe public health problem. The only country with a nationally representative sample was Mexico, which found 24%, 10%, 8%, and 10% prevalence rates of vitamin D insufficiency (25-hydroxyvitamin D < 50 nmol/L) in preschoolers, schoolchildren, adolescents, and adults, respectively. The prevalence of vitamin D deficiency (25-hydroxyvitamin D < 20 nmol/L) was less than 1% for all groups. Conclusions There is some indication that vitamin D insufficiency may be a public health problem in Latin America and the Caribbean, but the exact magnitude is currently unknown.
Update: Rural/Urban Disparities in Pneumococcal Vaccine Service Delivery Among the Fee-for-Service Medicare Population, 2012-2015

Department of Health and Human Services (HHS) under cooperative agreement # U1CRH30041. The information, conclusions and opinions expressed in this document are those of the authors and no endorsement by FORHP, HRSA, HHS, or the University of Kentucky is intended or should be inferred. ©2018 Rural & Underserved Health Research Center, University of Kentucky Update: Rural/Urban Disparities in Pneumococcal Vaccine Service Delivery Among the Fee-for-Service Medicare Population, 2012-2015
Model identification for time series with dependent innovations

This paper investigates the impact of dependent but uncorrelated inno- vations (errors) on the traditional autoregressive moving average model (ARMA) order determination schemes such as autocorrelation function (ACF), partial auto- correlation function (PACF), extended autocorrelation function (EACF), and the unit-root test. The ARMA models with iid innovations have been studied exten- sively and are well-posed, but their properties with dependent but uncorrelated innovations are relatively less studied. In the presence of such innovations, we show that the ACF, PACF, and EACF are significantly impacted while the unit- root test is not affected. We also propose a new order determination scheme to address those impacts for analyzing time series with uncorrelated innovations.
Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.
1,25‐dihydroxyvitamin D3 regulates the development of chronic colitis by modulating both T helper (Th)1 and Th17 activation

T helper (Th)1 and Th17 cells play a critical role in inflammatory bowel disease (IBD). 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) has emerged as a direct regulator of immune system function. Mice were grouped as follows: Control group (received PBS, n = 10), DSS group (received 2% DSS and PBS, n = 10), and DSS+VD group (received 2% DSS and 1,25(OH)2D3, n = 10). The disease activity index (DAI), colon length, and damage store of the mice were observed; the spleen length, weight, spleen index, and mononuclear cells of spleen were measured; mononuclear cells from mesenteric lymph nodes (MLN) were measured, and the levels of Th 1 and Th17 cytokines in the colon mucosa and spleen were measured. Mice in the DSS group developed severe diarrhea, rectal bleeding, and marked BW loss. Histological examination revealed extensive ulceration and inflammatory cell infiltration in the colon, and the structure of the spleen was disordered, infiltrated with inflammatory cytokines in red pulp. In the DSS group, mononuclear cell numbers from MLN and spleen were increased, and enhanced proteins and mRNA levels of Th 1 and Th17 cytokines were detected. In the DSS+VD group, 1,25(OH)2D3 ameliorated the inflammation of the colon and spleen. In addition, 1,25(OH)2D3 down‐regulated the levels of Th 1 and Th17 cytokines. 1,25(OH)2D3 represents a novel therapeutic drug for UC, which may correlate to inhibit the activation of Th1 and Th17 cells.
Access to Justice for families? Legal advocacy for parents where children are on the ‘edge of care’: an English case study

This paper examines the issue of professional advocacy for parents in England following the local authority issuing the Letter Before Proceedings when the concerns about the welfare of a child are so serious the local authority are considering applying for a care order. We explore the tensions of providing a legal advocacy service for parents – drawing on a study of 57 cases, scrutinised as part of the Coventry and Warwickshire Cafcass Pre-Proceedings Pilot (Broadhurst et al. 2012) and explores the contribution of legal representation for parents. The pre-proceedings meeting can be pivotal in terms of the direction of the case, the impression created at the meeting, and the action parties take afterwards. The importance of advocacy for parents was highlighted in the study both to facilitate parents' understanding of the issues, and to afford a level of protection of their rights. It is noteworthy that in 16 out of 82 pre-proceedings meetings no advocate was present, and in general fathers were less likely to be represented (although as reported the exact pattern appears more complex). Where advocates were present, contributions to the pre proceedings meeting varied from no input, to seeking points of clarification, and in 4 cases there was evidence of active ‘brokering’ on behalf of their clients.
Markdown or Everyday Low Price? The Role of Behavioral Motives

We study a seller’s optimal pricing and inventory strategies when behavioral (nonpecuniary) motives affect consumers’ purchase decisions. In particular, the seller chooses between two pricing strategies, markdown or everyday low price, and determines the optimal prices and inventory level. Two salient behavioral motives that impact consumers’ purchase decisions and the seller’s optimal strategies are anticipated regret and misperception of product availability. Regret arises when a consumer initially chooses to wait but encounters stockout later, or when the consumer buys the product at the high price but realizes that the product is still available at the markdown price. In addition, consumers often perceive the product’s future availability to be different than its actual availability. We determine and quantify that both regret and availability misperception have significant operational and profit implications for the seller. For example, ignoring these behavioral factors can result in up to 10% profit .
Stabilization of uncertain fuzzy time-delay systems via variable structure control approach

In view of a recent new application of variable structure control (VSC) to the stabilization problem for Takagi-Sugeno (T-S) fuzzy models, this paper aims to study the stabilization of uncertain fuzzy time-delay systems in T-S fuzzy model via VSC approach. There are mainly two features in this paper: one lies in the incorporation of time-delays (both smooth and nonsmooth delays) in which case Lyapunov functionals and Razumikhin Theorem are required to solve the stabilization problem; the other feature is that not only matched uncertainties but also mismatched uncertainties in the state variables are considered. As a sequence, the contribution of this paper consists of various control schemes proposed for the VSC design and the present results are in terms of linear matrix inequalities (LMIs). An illustrative example is given to show the effectiveness of our various results.
Effects of docosahexaenoic and arachidonic acids on the synthesis and distribution of aminophospholipids during neuronal differentiation of PC12 cells.

We have shown previously that docosahexaenoic acid (DHA) promotes and arachidonic acid (AA) suppresses neurite outgrowth of PC12 cells induced by nerve growth factor (NGF) and that incorporation of [3H]ethanolamine into phosphatidylethanolamine (PE) is suppressed in PC12 cells by AA while DHA has no effect. In the present study, the effects of these fatty acids on PE synthesis via decarboxylation of phosphatidylserine (PS), another pathway of PE synthesis, and distribution of aminophospholipids were examined. Incorporation of [3H]serine into PS and PE was elevated in the course of NGF-induced differentiation and was further stimulated significantly by DHA, but not by AA. [3H]Ethanolamine uptake by PC12 cells was significantly suppressed by AA but not by DHA while these fatty acids did not affect [3H]serine uptake, indicating that the suppression by AA of [3H]ethanolamine incorporation into phosphatidylethanolamine is attributable, at least in part, to a reduction in [3H]ethanolamine uptake. The distribution of PE in the outer leaflet of plasma membrane decreased during differentiation, which is known to be accompanied by an increase in the surface area of plasma membrane. Supplementation of PC12 cells with DHA or AA did not affect the distribution of aminophospholipids. Thus, DHA and AA affected aminophospholipid synthesis and neurite outgrowth differently, but not the transport and distribution of aminophospholipids, while the PE concentration in the outer leaflet of the plasma membrane decreased in association with morphological changes in PC12 cells induced by NGF.
Differential response of human gingival fibroblasts to titanium- and titanium-zirconium-modified surfaces.

BACKGROUND AND OBJECTIVE Gingival fibroblasts are responsible for the constant adaptation, wound healing and regeneration of gingival connective tissue. New titanium-zirconium (TiZr) abutment surfaces have been designed to improve soft tissue integration and reduce implant failure compared with titanium (Ti). The aim of the present study was first to characterize a primary human gingival fibroblast (HGF) model and secondly to evaluate their differential response to Ti and TiZr polished (P), machined (M) and machined + acid-etched (modMA) surfaces, respectively. MATERIAL AND METHODS HGF were cultured on tissue culture plastic or on the different Ti and TiZr surfaces. Cell morphology was evaluated through confocal and scanning electron microscopy. A wound healing assay was performed to evaluate the capacity of HGF to close a scratch. The expression of genes was evaluated by real-time RT-PCR, addressing: (i) extracellular matrix organization and turnover; (ii) inflammation; (iii) cell adhesion and structure; and (iv) wound healing. Finally, cells on Ti/TiZr surfaces were immunostained with anti-ITGB3 antibodies to analyze integrin β3 production. Matrix metalloproteinase-1 (MMP1) and inhibitor of metallopeptidases-1 (TIMP1) production were analyzed by enzyme-linked immunosorbent assays. RESULTS On tissue culture plastic, HGF showed no differences between donors on cell proliferation and on the ability for wound closure; α-smooth muscle actin was overexpressed on scratched monolayers. The differentiation profile showed increased production of extracellular matrix components. Ti and TiZr showed similar biocompatibility with HGF. TiZr increased integrin-β3 mRNA and protein levels, compared with Ti. Cells on TiZr surfaces showed higher MMP1 protein than Ti surfaces, although similar TIMP1 protein production. In this in vitro experiment, P and M surfaces from both Ti and TiZr showed better HGF growth than modMA. CONCLUSION Taking into account the better mechanical properties and bioactivity of TiZr compared with Ti, the results of the present study show that TiZr is a potential clinical candidate for soft tissue integration and implant success.
The Atlanta FICSIT Study: Two Exercise Interventions to Reduce Frailty in Elders

This study examines the effect of two different exercise approaches on balance and frailty measures among more than 200 community‐dwelling individuals greater than 70 years of age. Exercises are provided for 15 weekly sessions on an individual basis for participants randomly assigned to a Balance Training group. Training consists of center‐of‐mass feedback displayed on a motor under static conditions, or, in later sessions, as the floor surface is moved, with eyes open or closed. This high technology interface provides instantaneous information about displacement of body weight in space so that balance can be enhanced. An alternative procedure is comparatively simple and requires little expense or space. Tai Chi Quan was originally developed as a martial arts form but has been used for centuries in China as an exercise among elderly citizens. Participants randomly assigned to this intervention meet twice weekly for 15 weeks to learn a condensation of 108 Tai Chi forms into 10 that emphasize movement components often restricted or absent with aging. A third group serves as a control for exercise interventions by meeting weekly for 15 sessions to discuss topics of interest such as memory loss, drug management, and nutrition. All subjects are screened prior to assignment, and a host of physical, behavioral, and functional measures are assessed before and after the intervention as well as 4 months later. Measurements unique to the Atlanta site include: balance with eyes closed, programmed force‐distribution changes when stance is perturbed, cardiovascular assessments, WAIS, Affects Balance Scale, and a survey of home environment.