Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti‐phospholipid antibodies following vaccination with recombinant hepatitis B vaccine

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti‐cardiolipin antibodies (aCL), antibodies against β2GPI (anti‐β2GPI), lupus anti‐coagulant (LA), anti‐nuclear antibodies and antibodies against extractable nuclear antigens (anti‐ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20·8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti‐β2GPI or LA activity (P < 0·001). Among subjects in whom changes of IgG anti‐β2GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P < 0·01). Analyses of paired data showed that differences in aCL or anti‐β2GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti‐β2GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti‐β2GPI and the levels were increasing after vaccination. Two participants became positive for anti‐nuclear antibodies during 6 months’ follow‐up. There were no sex‐dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti‐HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.
[Dose-dependent side effects of acetylsalicylic acid therapy. Results of a prospective randomized clinical study in patients with peripheral arterial occlusive disease].

BACKGROUND AND METHODS In 359 patients with peripheral arterial occlusive disease who had undergone percutaneous transluminal angioplasty (PTA), a randomized double-blind, controlled clinical study was done to investigate the tolerability of acetyl salicylic acid (ASA) given for reocclusion prophylaxis. A comparison was made between a conventional daily dose of 900 mg ASA and a dose of 50 mg ASA. RESULTS Within an observation period of one year following PTA, 35 patients (20%) in the 900 mg group, and 32 patients (17%) in the 50 mg group left the trial because of side effects (p = NS). Under the higher dose, however, severe gastrointestinal side effects (ulcer, haemorrhagic gastritis requiring transfusion) were significantly more common (nine patients delta 5.1% vs two patients delta 1.1%, respectively; p = 0.03). Overall, 107 patients (30%) reported subjective side effects such as upper abdominal pain, a sensation of fullness or nausea during the course of the trial. 62 of these patients were from the 900 mg group (35%) as compared with 45 patients (24%) in the 50 mg group (p = 0.02). Self-scoring of epigastric pain on the basis of a visual analogue scale revealed a score of 1.3 (95% confidence interval 0.9 to 1.6) in the 900 mg group and 0.8 (95% confidence interval 0.6 to 1.0) in the 50 mg group. The subjective pain intensity showed a uniform time course for all three types of symptom, with a maximum after three months. CONCLUSION Our results confirm the superior tolerability of the lower dose, in particular in elderly patients. For long-term treatment, the smallest possible effective dose should be chosen.
Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

ABSTRACT In livers of susceptible but self-curing C57BL/6 mice, intracellular Leishmania donovani infection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4−/− mice showed reduced gamma interferon (IFN-γ), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-γ to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2−/− mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy's efficacy enhanced. In livers of infected TLR2−/− mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-γ/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy's effect. Thus, in experimental L. donovani infection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).
Do we still need the surgeon to close the persistently patent arterial duct?

Summary The data from the reports we have reviewed showsthat transcatheter closure of the persistently patentarterial duct causes minimal pain, and has a very lowrate of complications. Embolization is becoming veryrare. The procedural and fluoroscopic times are accept-able. If all the devices available for clinical use areaccessible, with rare exceptions, almost every sizeand type of patent duct can be closed successfullyusing the interventional transcatheter approach. Mostdevices produce a very high rate of complete occlusion.The patients can be sent home less than 24 hoursafter intervention. Regular follow-up is still neededto assess long-term safety and efficacy of the devices. Place in clinical management andfuture outlook Studies dealing with the patent arterial duct arerarely prospective, and almost never randomized.With such a malformation, a lower level of evidencethan randomized studies is accepted to alter man-agement. Hence, it is acceptable to rely on consensusmeetings, clinical recommendations of scientificsocieties, and national registries. Recommendationsfor management made by respected societies, how-ever, rarely take economic factors into considera-tions.
Antiapoptotic but Not Antiviral Function of Humanbcl-2 Assists Establishment of Japanese Encephalitis Virus Persistence in Cultured Cells

ABSTRACT Upon infection of Japanese encephalitis virus (JEV), baby hamster kidney (BHK-21) and Chinese hamster ovary (CHO) cells were killed by a mechanism involved in apoptosis. While readily established in a variety of cell lines, JEV persistence has never been successfully instituted in BHK-21 and CHO cells. Since stable expression of humanbcl-2 in BHK-21 cells has been shown to delay JEV-induced apoptosis, in this study we investigated whether JEV persistence could be established in such cells. When constitutively expressing bcl-2, but not its closest homolog,bcl-XL , following a primary lytic infection, approximately 5 to 10% of BHK-21 and CHO cells became persistently JEV infected during a long-term culture. From the persistent bulks, several independent clones were selected and expanded to form stable cell lines that continuously produced infectious virus without marked cytopathic effects (CPE). Among these stable cell lines, the truncated nonstructural protein 1 (NS1) was also detected and was indistinguishable from the NS1 truncations previously observed in JEV-persistent murine neuroblastoma N18 cells. However, the stable expression of NS1 alone, regardless of whether it was truncated or full length, failed to render the engineered cells persistently infected by JEV, implying that aberrant NS1 proteins were likely a consequence of, rather than a cause for, the viral persistence. Enforcedbcl-2 expression, which did not affect virus replication and spread during the early phase of cytolytic infection, appeared to attain JEV persistence by restriction of virus-induced CPE. Our results suggest that it is the antiapoptotic, rather than the antiviral, effect of cellularbcl-2 which plays a role in the establishment of JEV persistence.
Studies on Some 3(2H)‐Pyridazinone Derivatives with Antinociceptive Activity

Nineteen new [6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]‐acetamide (1—10) and 3‐[6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]propanamide (11—19) derivatives have been synthesized in this study. The structures of the compounds have been elucidated by their IR and NMR spectral data and elemental analysis. Antinociceptive activity of the compounds has been investigated by modified Koster's Test in mice, using aspirin as a reference. All the compounds (at 100 mg/kg dose) except >1 and 9 have been found more potent than aspirin. Compound 6 in the group of acetamide derivatives and compound 15 in the group of propanamides exhibited the highest antinociceptive activity. In addition, the propanamides have generally been found more potent than acetamides. In addition to these studies, the quantitative relation‐ships between some structural parameters (such as log P, parachor, molar refractivity, and molecular connectivity indices) and antinociceptive activity of the compounds have been investigated. Statistical regression analysis has shown a close relationship to exist between the first‐order molecular connectivity index (1 χ) and the antinociceptive activity.
Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients.

PURPOSE Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma. METHODS Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital (Copenhagen, Denmark) for detection of RNA binding protein with multiple splicing (RBPMS) and melanopsin by immunohistochemistry. The density of RBPMS-expressing RGCs and mRGCs in each retina was estimated as the total cell count in the total retinal area analyzed (cell counts/mm2). RESULTS No significant difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts/mm2, with 75% of all retained mRGCs occurring in the inner nuclear layer. CONCLUSIONS This is the first report illustrating histologic evidence for reduced mRGC density in the ganglion cell layer of retinas with severely staged glaucoma compared with age-matched controls. This result proposes evaluation of mRGCs integrity as a basis for assessing the pathophysiologic disease progression of glaucoma.
Thoracic geometry changes during equine locomotion

Classic descriptions of rib motion during ventilation include three-dimensional movements that are tied to the locomotor pattern. It is still not clear how chest wall and diaphragmatic movements contribute to ventilation. The purpose of this paper was to evaluate how gait affects local thoracic geometry in horses. Hemispherical markers were placed on the skin over the ribs and spine to calculate thoracic hemi-diameter. Ventilatory airflows were recorded using an ultrasonic flowmeter system. Airflow and kinematic data were collected synchronously at walk (1.8 m s -1 ), trot (4 m s -1 ), canter and gallop (6, 8 and 10 m s -1 ) on the treadmill. At walk and trot, the changes in right and left hemi-diameter were approximately symmetric. At walk, mean hemi-diameter changes were 40 mm (rib 10) and 47 mm (rib 16). At trot, they were 33 mm (rib 10) and 34 mm (rib 16). Across the three canter and gallop speeds, leading (right) side hemi-diameter change increased from 25 to 30 to 35 mm (rib 10) and from 23 to 37 to 46 mm (rib 16). The trailing (left) side hemi-diameter increased from 50 to 67 to 70 mm (rib 10) and from 36 to 48 to 54 mm (rib 16) ( P ≪0.01). At canter and gallop, the non-lead side of the thorax is subjected to larger amplitude changes in hemi-diameter than the lead side, which tends to be more compressed overall and demonstrates smaller amplitudes of change in diameter.
Alterations of DNA Copy Number and Expression in Genes Involved in Cell Cycle Regulation and Apoptosis Signal Pathways in γ-Radiation-Sensitive SX9 Cells and -Resistant SR-1 Cells

Abstract Koshikawa, T. , Uematsu, N. , Iijima, A. , Katagiri, T. and Uchida, K. Alterations of DNA Copy Number and Expression in Genes Involved in Cell Cycle Regulation and Apoptosis Signal Pathways in γ-Radiation-Sensitive SX9 Cells and -Resistant SR-1 Cells. Radiat. Res. 163, 374–383 (2005). In the present study, genomic differences related to sensitivity to radiation were examined by comparative genomic hybridization and GeneChip 45K microarray in SX9 cells (radiation-sensitive) and their parental line, SR-1 (radiation-resistant). SX9 cells have defective DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity. DNA-PKcs is a DNA double-strand break repair protein that maintains chromosomal stability through nonhomologous end joining. However, the molecular basis of the radiation sensitivity of SX9 cells is unclear. Flow cytometry analysis showed that SR-1 and SX9 cells had a larger G2/M-phase population at 12 h after 4 Gy γ irradiation, while only SR-1 cells progressed to G1/S at 24–36 h. SX9 and SR-1 cells had similar patterns of DNA copy number alteration, but the gains were observed on chromosome 9 (cent-E2), 11 (cent-A3), and 12 (C1-E) only in SX9 cells. Expression of genes located on those regions is higher in SX-9 cells than in SR1 cells, and the regions include genes associated with apoptosis and cell cycle regulation. Time-course data for gene expression at 0, 1, 3, 6 and 12 h after 4 Gy γ irradiation revealed that the genes whose expression was altered in SX9 cells but not in SR-1 cells are in 16 clusters. Three of these clusters included genes for cell cycle regulation: JNK, PKC (PRKC) and ceramide cascade protein. These results suggest that amplification and altered expression of genes associated with cell cycle and apoptosis regulators in DNA-PK-deficient SX9 cells affect the differences in response to γ radiation between SX9 and SR-1 cells.
Atypical Face Perception in Autism: A Point of View?

Face perception is the most commonly used visual metric of social perception in autism. However, when found to be atypical, the origin of face perception differences in autism is contentious. One hypothesis proposes that a locally oriented visual analysis, characteristic of individuals with autism, ultimately affects performance on face tasks where a global analysis is optimal. The objective of this study was to evaluate this hypothesis by assessing face identity discrimination with synthetic faces presented with and without changes in viewpoint, with the former condition minimizing access to local face attributes used for identity discrimination. Twenty‐eight individuals with autism and 30 neurotypical participants performed a face identity discrimination task. Stimuli were synthetic faces extracted from traditional face photographs in both front and 20° side viewpoints, digitized from 37 points to provide a continuous measure of facial geometry. Face identity discrimination thresholds were obtained using a two‐alternative, temporal forced choice match‐to‐sample paradigm. Analyses revealed an interaction between group and condition, with group differences found only for the viewpoint change condition, where performance in the autism group was decreased compared to that of neurotypical participants. The selective decrease in performance for the viewpoint change condition suggests that face identity discrimination in autism is more difficult when access to local cues is minimized, and/or when dependence on integrative analysis is increased. These results lend support to a perceptual contribution of atypical face perception in autism. Autism Res 2015, 8: 497–506. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Squeezing the antibiotic balloon: the impact of antimicrobial classes on emerging resistance

ABSTRACT The ongoing problem of emerging antimicrobial resistance has been likened to a balloon where settling one specific issue results in a ‘bulge’ of even worse problems. However, much has been learned about how to best use our critical antibacterial agents in ways to avoid or even repair some of the resistance damage that has been done. A compilation of current literature strongly suggests that to slow the development of resistance to antimicrobial agents it is optimal to use drugs with more than one mechanism of action or target, to prescribe those with demonstrated ability to minimise or reverse resistance problems, and to avoid underdosing of potent antibiotics. The most recent information also indicates that it is best to limit empirical use of β-lactam plus fluoroquinolone combination therapy, since these two classes activate some common resistance responses, and using them together can facilitate multidrug resistance in important pathogens, particularly Pseudomonas aeruginosa and Acinetobacter species. This review discusses the role of each major antimicrobial class on resistance development and presents specific strategies for combating the growing problem of multidrug-resistant bacteria. We now have the knowledge to better manage our antimicrobial agent prescribing practices, but finding the will and resources to apply our understanding remains a formidable challenge.
Factors Associated With Human Papillomavirus Infection Detected by Polymerase Chain Reaction Among Urban Canadian Aboriginal and Non‐Aboriginal Women

Objectives: To determine the prevalence and correlates of human papillomavirus (HPV) infection among women attending an ethnically mixed, predominantly low‐income, inner‐city primary care clinic. Study Design: Cross‐sectional survey (N = 1,477). Demographic, behavioral, and reproductive history data were collected by questionnaire. Cervical swabs were analyzed for gonorrhea and chlamydial infections, abnormal cytology, and HPV infection assessed by PCR followed by hybridization for types 6, 11, 16, 18, 31, 33, and 35. Results: Human papillomavirus was detected in 33% of specimens, with no significant difference between Aboriginal (AB) and non‐Aboriginal women. Adjusting for AB status, HPV infection was associated with marital status, condom use, number of sexual partners (last year and lifetime), age at first sexual intercourse, a history of sexual abuse, and current abnormal Papanicolaou (Pap) smear. In multivariate analyses excluding abnormal Pap smear as an independent variable, marital status and the number of lifetime sexual partners were found to be significant independent predictors of HPV infection. Comparing individuals with 20+ lifetime sexual partners and those with 1 or fewer partners, the odds ratio (OR) for HPV infection was 1.90 (95% confidence interval [CI] 1.66–2.17) among AB women and 1.54 among non‐AB women (95% CI 1.36–1.73). The OR for infection with HPV types 6 and 11 was 1.39 (95% CI 1.22–1.58), whereas for the high oncogenic risk types of 16, 18, 31, 33, and 35, the OR was 1.82 (95% CI 1.65–2.01). Conclusions: No differences were found between AB and non‐AB women in the detection of HPV DNA, despite the higher risk for cervical cancer and the prevalence of recognized behavioral and reproductive risk factors among AB women. This study also indicates that the association of sexual activity with HPV infection holds true for both high‐ and low‐oncogenic HPV types.
Needed, new paradigms in antibiotic development

While antibiotic resistance has grabbed the headlines and the attention of the pharmaceutical industry, the lack of susceptibility of biofilms formed both on animate and inanimate surfaces deserve greater attention from the industry, medical practitioners and regulators. The current literature tells us that the inherent tolerance to antibiotics demonstrated by antibiotic-sensitive organisms when grown as a biofilm clearly identifies a major disconnect between our current practices in antimicrobial development, diagnostics and efficacy in patient treatment. A paradigm shift is required in the way we utilize conventional antimicrobials and in the way we screen for next-generation antibiotics with efficacy to treat biofilms associated with chronic, recurrent and device related infections. This paradigm shift must not only take place in industry but also in how drugs are brought to the marketplace for acceptance.
Niemann–Pick disease type C

Niemann‐Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage with a wide spectrum of clinical phenotypes. At the cellular level, the disorder is characterized by accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system. Approximatively 95% of patients have mutations in the NPC1 gene (mapped at 18q11) which encodes a large membrane glycoprotein primarily located to late endosomes. The remainder have mutations in the NPC2 gene (mapped at 14q24.3) which encodes a small soluble lysosomal protein with cholesterol‐binding properties. The identical biochemical patterns observed in NPC1 and NPC2 mutants suggest that the two proteins function in a coordinate fashion. Identification of mutations revealed a complex picture of molecular heterogeneity, allowing genotype ‐ phenotype correlations for both genes and providing insights into structure ‐ function relationships for the NPC1 protein. Although a whole body of evidence suggests that the NPC1 and NPC2 proteins are involved in the cellular postlysosomal/late endosomal transport of cholesterol, glycolipids and other cargo, their precise functions and relationship remain unclear and are currently the subject of intense investigation. These studies, conducted in various models, should ultimately lead to a better understanding of the pathophysiology of NPC and new therapeutic approaches.
Phytoextraction Potential of Wild Type and 35S-GSHI Transgenic Poplar Trees (Populus × Canescens) for Environmental Pollutants Herbicide Paraquat, Salt Sodium, Zinc Sulfate and Nitric Oxide In Vitro

Phytoextraction potentials of two transgenic (TR) poplar (Populus × canescens) clones TRggs11 and TRlgl6 were compared with that of wild-type (WT) following exposure to paraquat, zinc sulfate, common salt and nitric oxide (NO), using a leaf-disc system incubated for 21 days on EDTA-containing nutritive WPM media in vitro. Glutathione (GSH) contents of leaf discs of TRlgl6 and TRggs11 showed increments to 296% and 190%, respectively, compared with WT. NO exposure led to a twofold GSH content in TRlgl6, which was coupled with a significantly increased sulfate uptake when exposed to 10−3 M ZnSO4. The highest mineral contents of Na, Zn, Mn, Cu, and Mo was observed in the TRggs11 clone. Salt-induced activity of catalase enzyme increased in both TR clones significantly compared with WT under NaCl (0.75% and 1.5%) exposure. The in silico sequence analyses of gsh1 genes revealed that P. × canadensis and Salix sachalinensis show the closest sequence similarity to that of P. × canescens, which predicted an active GSH production with high phytoextraction potentials of these species with indication for their use where P. × canescens can not be grown.