Miracle-dz/UniFAR-FTUs huggingface dataset:
Uridine in the Prevention and Treatment of Nrti-Related Mitochondrial Toxicity

Long-term side effects of antiretroviral therapy are attributed to the mitochondrial (mt) toxicity of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their ability to deplete mtDNA. Studies in hepatocytes suggest that uridine is able to prevent and treat mtDNA depletion by pyrimidine NRTIs [zalcitabine (ddC) and stavudine (d4T)] and to fully abrogate hepatocyte death, elevated lactate production and intracellular steatosis. Uridine was also found to improve the liver and haematopoietic toxicities of zidovudine (AZT), which are unrelated to mtDNA depletion, and to prevent neuronal cell death induced by ddC. Most recently, uridine was found to prevent the onset of a lipoatrophic phenotype (reduced intracellular lipids, increased apoptosis, mtDNA depletion and mt depolarization) in adipocytes incubated long-term with d4T and AZT. Various steps of mt nucleoside utilization may be involved in the protective effect, but competition of uridine metabolites with NRTIs at polymerase y or other enzymes is a plausible explanation. Pharmacokinetic studies suggest that uridine serum levels can be safely increased in humans to achieve concentrations which are protective in vitro (50–200 μM). Uridine was not found to interfere with the antiretroviral activity of NRTIs. Mitocnol, a sugar cane extract which effectively increases uridine in human serum, was beneficial in individual HIV patients with mt toxicity and is now being tested in placebo-controlled randomized trials. Until these data become available, the risk-benefit calculation of using uridine should be individualized. The current safety data justify the closely monitored use of uridine in individuals who suffer from mt toxicity but who cannot be switched to less toxic NRTIs.
Gender, citizenship and dementia care: a scoping review of studies to inform policy and future research

Gender is a neglected dimension in public discourse related to people with dementia. Those living with this condition are typically portrayed in policies and strategies in gender neutral terms as 'people with dementia' and 'family carers' as if gender does not matter, when clearly it does. The purpose of this scoping review was to take stock of knowledge about gender differences in relation to dementia care to inform policy and future research. The work is grounded in a feminist perspective to citizenship, as this provide a lens with which to expose and examine gendered assumptions within dementia studies. A search of four databases, including CINAHL, Web of Science, Medline and Cochrane was conducted using systematic techniques between May and July 2014. A repeat search was conducted in February 2015. We found a significant amount of valuable research concerned with gender differences in relation to dementia care published from 1990 to 2014; the majority of which lacks a feminist citizenship perspective. Moreover, a disproportionate number of studies focused solely on caregivers rather than citizens with dementia. As such, questions about gender equality are not being raised and the voices of men and women with dementia are silent. Thus we argue for increased gender-sensitivity in policy making and recommend that social scientists inject a feminist citizenship perspective into their work.
Constructing part-based models for groupwise registration

We address the problem of building detailed models of the shape and appearance of complex structures, given only a training set of representative images and some minimal manual intervention. We focus on objects with repeating structures (such as bones in the hands), which can cause normal deformable registration techniques to fall into local minima and fail. Using a sparse annotation of a single image we can construct a parts+geometry model capable of locating a small set of features on every training image. Iterative refinement leads to a model which can locate structures accurately and reliably. The resulting sparse annotations are sufficient to initialise a dense groupwise registration algorithm, which gives a detailed correspondence between all images in the set. We demonstrate the method on a large set of radiographs of the hand, achieving sub-millimeter accuracy.
Running head : Piromelatine ameliorates glucose impairment in IR rats

The melatonin receptor agonist piromelatine ameliorates impaired glucose metabolism in chronically stressed rats fed a high-fat diet Authors: Jun Zhou, Deng Wang, XiaoHong Luo, Xu Jia, MaoXing Li, Moshe Laudon, RuXue Zhang, and ZhengPing Jia Author affiliations: College of Pharmacy, Lanzhou University, Lanzhou 730000, PR China (J.Z, M.L, R.Z., Z.J.); Lanzhou General Hospital of PLA, Lanzhou 730050, PR China (J.Z, X.L., M.L, R.Z., Z.J.); Xi’an Daxing Hospital, Shaanxi 710016, PR China (D.W.); Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China (X.J.); Drug Discovery, Neurim Pharmaceuticals Ltd., Tel-Aviv, Israel (M.L.) This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on October 12, 2017 as DOI: 10.1124/jpet.117. 243998
Gliadin Antibodies in Adult Insulin-Dependent Diabetes - Autoimmune and Immunogenetic Correlates

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p=0.003, and 69 vs. 27%, p<0.001, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-1 patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRBl*03-DQBl*02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1 * 13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD
Percutaneous nerve field stimulation (PENS) of the occipital region as a possible predictor for occipital nerve stimulation (ONS) responsiveness in refractory headache disorders? A feasibility study

Background Occipital nerve stimulation (ONS) has been reported to diminish pain levels in intractable chronic headache syndromes of different origin. No reliable objective markers exist to predict ONS responsiveness. This study investigated the predictive value of occipital percutaneous nerve field stimulation (PENS) prior to ONS. Methods This trial included 12 patients (CCH, CM, PTH, CH) with chronic refractory headache syndromes eligible for ONS. Repetitive PENS (3 × /10 days) was performed and the headache severity/frequency monitored over four weeks before ONS implantation. Further assessment of PENS/ONS outcomes were stimulation-related complications, perception/tolerance stimulation threshold, the Migraine Disability Scale (MIDAS) and the Beck Depression Inventory (BDI). Results All PENS responders benefited from ONS. Of the seven PENS-nonresponders with VAS 6.1(±1.1), six experienced significant pain relief from ONS after three months and one patient failed the PENS/ONS trial (VAS 3.7 (±1.6)); (95% CI 3.6 to 5.7, p < 0.001). The VAS baseline was 8.4 (±0.5) and decreased significantly (50% reduction in severity/frequency) in five patients after PENS, while seven failed to improve (VAS 4.9 (±1.1); (95% CI 2.5 to 4.5, p < 0.001). BDI baseline (from 22.6 (±4.2) to 10.6 (±5.9) (95% CI 7.4 to 16.6, p < 0.001)) and MIDAS baseline (from 143.9 (±14.5) to 72.8 (±28.7) (95% CI 1.17 to 2.3, p < 0.001)) significantly declined after ONS. No PENS/ONS-related complications occurred. Conclusions Presurgical applied occipital PENS failed to identify ONS responders sufficiently according to our study protocol, thus requiring further specific investigations to determine its predictive usefulness.
Prolonged elevation of serum granulysin in drug‐induced hypersensitivity syndrome

and soluble CD40 ligand in serum and plasma. J Thromb Haemost 2004; 11:2067–9. 6 Kasperska-Zajac A, Sztylc J, Machura E, Jop G. Plasma IL-6 concentration correlates with clinical disease activity and serum C-reactive protein concentration in chronic urticaria patients. Clin Exp Allergy 2011; 41:1386–91. 7 Toubi E, Adir-Shani A, Kessel A et al. Immune aberrations in B and T lymphocytes derived from chronic urticaria patients. J Clin Immunol 2000; 20:371–8. 8 Hermes B, Worm M, Nowak F et al. Upregulation of CD40 and CD40 ligand expression in IgE-associated cutaneous diseases. Acta Derm Venereol 1997; 77:441–5. 9 Kasperska-Zajac A, Rogala B. Platelet activation during allergic inflammation. Inflammation 2007; 30:161–6. 10 Kasperska-Zając A, Rogala B, Nowakowski M. Assessment of platelet activity as expressed by plasma levels of platelet factor 4 and b-thromboglobulin in patients with chronic idiopathic urticaria. Exp Dermatol 2005; 14:515–18. 11 Kasperska-Zajac A, Brzoza Z, Rogala B. Platelet function in cutaneous diseases. Platelets 2008; 19:317–21. 12 Kasperska-Zajac A. Acute phase response in chronic urticaria. J Eur Acad Dermatol Venereol 2011; (in press). 13 Kasperska-Zając A, Grzanka A, Czecior E, Misiolek M, Rogala B, Machura E. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria ⁄angioedema and after aspirin challenge. J Eur Acad Dermatol Venereol 2012; 21 February. doi: 10.1111/j.1468-3083.2012. 04486.x.
Role of protein kinase C in nonsensitized and passively sensitized human isolated bronchial smooth muscle.

To examine the role of protein kinase C (PKC) activation in the control of the mechanical activity of human isolated bronchial smooth muscle obtained at thoracotomy, the effect of the phorbol ester phorbol 12,13-dibutyrate (PDB) was evaluated. PDB produced slowly developing and sustained contractions that were reduced 1) by the PKC inhibitor staurosporine and 2) after long-term (12 h) exposure to PDB, which downregulates PKC. Moreover, the inactive phorbol ester 4 alpha-phorbol 12,13 didecanoate had no contractile effect. Removal of external Ca2+ or addition of the Ca(2+)-channel antagonist verapamil reduced the PDB-induced contraction. Passive sensitization of human isolated bronchial rings, i.e., incubation overnight of tissues in serum from atopic asthmatic patients, decreased the maximal response to PDB to 28.9 +/- 8% of the maximal response to acetylcholine (ACh) when compared with that of paired nonsensitized rings, i.e., tissues incubated overnight in serum from normal subjects (46.7 +/- 9.4% of the maximal response to ACh, n = 5, P < 0.05). The decrease in the response to PDB induced by either long-term preexposure to PDB or passive sensitization was reversed when both types of tissues were allowed to recover unstimulated for 3 h before PDB application. These results show that 1) PKC activation induces maintained contractions in human isolated airway smooth muscle that are largely dependent on extracellular calcium; 2) passive sensitization alters the PKC-mediated response in a way similar to that induced by prolonged stimulation of PKC.
Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells.

The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus. This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES). Cells were treated with proinflammatory molecules and mimics of infection [lipopolysaccharide (LPS) and lipoteichoic acid (LTA)]. mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR. HBD1 mRNA was present at very low levels preventing conclusive study of its regulation. However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha. SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha. LPS had little effect on antimicrobial expression. However, there was a trend towards increased expression with LTA treatment for 4-8 h. Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment. These results suggest that in endometrium some natural antibiotics (e.g. SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g. HBD2) are inducible allowing maximal antimicrobial activity during infection. Natural antimicrobials will have an important role in endometrium in protecting against infection.
Current classifications of pyramidal cells are based on the cells ’ firing patterns as well as the shape of their action potentials (

Zaitsev AV, Povysheva NV, Gonzalez-Burgos G, Lewis DA. Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex. J Neurophysiol 108: 595–609, 2012. First published April 11, 2012; doi:10.1152/jn.00859. 2011. —The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron’s functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.
Promoting Academic Integrity in an Online RN‐BSN Program

Aim. The goal of this quasi‐experimental study was to investigate an academic integrity (AI) intervention in an online RN to BSN nursing program. Background. Academic integrity is an issue in academia, with problems in this area increased by the proliferation of online and alternative learning environments. Method. Students newly admitted to a RN to BSN nursing program were randomly assigned to a control group (n = 169), which received the usual honor code exposure, or a treatment group (n = 177), which received a faculty‐designed intervention. At the completion of the semester, students were asked to complete an academic integrity survey tool. Results. Overall self‐reported cheating was very low in both groups. Students in the treatment group reported higher levels of faculty and student support for AI policies and perceived these policies to be more effective (p < .05). Conclusions. While more research is needed in the area of AI, especially in post‐licensure nursing students, faculty‐initiated discussions appear to foster a culture of AI.
Normalized wall index specific and MRI-based stress analysis of atherosclerotic carotid plaques: a study comparing acutely symptomatic and asymptomatic patients.

BACKGROUND Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. METHODS AND RESULTS 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for nite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). CONCLUSIONS Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies.
Evaluation of a new website design for iwantthekit for chlamydia, gonorrhea, and trichomonas screening.

The www.iwantthekit. org provides Internet-based, at-home sexually transmitted infection screening. The Web site implemented an automated test result access system. To evaluate potential deleterious effects of the new system, we analyzed demographics, Web site usage, and treatment. The post-Web site design captured more participant information and no decrease in requests, kit return, or treatment adherence.
Optimizing Primary Care Telephone Access and Patient Satisfaction

Telephone medicine is often preferred by patients to meet primary care needs and may be associated with high patient satisfaction. This article presents findings about incoming patient calls to primary care for medically based reasons during office hours and reports factors independently associated with telephone encounter satisfaction, considering patient characteristics, call reasons, and staff responsiveness, for a national cohort of primary care users. Interviews were conducted with patients from 18 nationwide primary care clinics during the fall of 2009. Calling for an urgent medical issue was associated with dissatisfaction. Odds of call satisfaction were greater when patients thought staff was friendly (10x), call answer was timely (5x), and needed medical information was provided (7x). These findings can be used for interventions to optimize telephone access and patient satisfaction which is beneficial because satisfactory telephone encounters reduce primary care use and satisfied patients are more likely to be engaged in their health care.
FK506 AS THE SOLE IMMUNOSUPPRESSIVE AGENT FOR PROLONGATION OF ISLET ALLOGRAFT SURVIVAL IN THE RAT

The purpose of the present study was to determine immunosuppressive effects of a new immunosuppressive agent, FK506, on rat islet allografts and also whether FK is toxic to the islet grafts since the diabetogenic effects of FK is controversial. Hand-picked clean fresh islets (WKA/Qdj:RT1u) were transplanted either beneath the renal capsule or into the liver via the portal vein of the diabetic (STZ, 60 mg/kg) rats (Lewis: RT11). FK506 was administered s. c. for 7 days after transplantation. The mean survival times (MST)* of the renal subcapsular grafts receiving 0 (control), 0.32 or 1.0 mg/ kg FK were 7.2 ± 1.1 (mean ± SD, n = 5), 13.8 ± 4.8 (n = 4), and 20.2 ± 8.0 days (n = 5), respectively. The MST of the intrahepatic grafts receiving 0, 0.1, 0.32, or 1.0 mg/kg FK were 4.4 ± 1.1 (n = 5), 7.2 ± 0.8 (n = 5), > 45.3 ± 23.1 (n = 6) or > 54.4±8.8 days (n = 5), respectively. Histologically, islets were found easily in the liver of normoglycemic recipients for more than 60 days after transplantation and appeared intact, with well-granulated beta cells. Foci of mononuclear cells were occasionally seen adjacent to the islet cells. The plasma glucose of the recipients with 1.0 mg/kg FK fluctuated between 150 and 350 mg/dl without rejection. In the recipients treated with 3.2 mg/kg FK the plasma glucose of all the recipients (n = 3) returned to pretransplant levels by 21 days after transplantation. However, islet cells were present in the liver of all these recipients without mononuclear cell infiltration. Immunohisto-chemically islet grafts stained weakly for insulin, but to the same extent as the controls for glucagon and somatostatin. These findings clearly demonstrate the immunosuppressive effect of FK506 on islet allografts and the importance of the transplant site for prolongation of graft survival by FK, and also suggest that FK has toxic effects on the islet grafts (B cells) when used in high dosages.
Linear and nonlinear tails I: general results and perturbation theory

For nonlinear wave equations with a potential term, we prove pointwise space-time decay estimates and develop a perturbation theory for small initial data. We show that the perturbation series has a positive convergence radius by a method which reduces the wave equation to an algebraic one. We demonstrate that already first and second perturbation orders, satisfying linear equations, can provide precise information about the decay of the full solution to the nonlinear wave equation.