Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of gap junctional coupling in astrocytic networks in the determination of global ischaemia‐induced oxidative stress and hippocampal damage

While there is evidence that gap junctions play important roles in the determination of cell injuries, there is not much known about mechanisms by which gap junctional communication may exert these functions. Using a global model of transient ischaemia in rats, we found that pretreatment with the gap junctional blockers carbenoxolone, 18α‐glycyrrhetinic acid and endothelin, applied via cannulae implanted into the hippocampus in one hemisphere, resulted in decreased numbers of TUNEL‐positive neurons, as compared with the contralateral hippocampus that received saline injection. Post‐treatment with carbenoxolone for up to 30 min after the stroke injury still resulted in decreased cell death, but post‐treatment at 90 min after the ischaemic insult did not result in differences in cell death. However, quinine, an inhibitor of Cx36‐mediated gap junctional coupling, did not result in appreciable neuroprotection. Searching for a possible mechanism for the observed protective effects, possible actions of the gap junctional blockers in the electrical activity of the hippocampus during the ischaemic insult were assessed using intracerebral recordings, with no differences observed between the saline‐injected and the contralateral drug‐injected hippocampus. However, a significant reduction in lipid peroxides, a measure of free radical formation, in the hippocampus treated with carbenoxolone, revealed that the actions of gap junctional coupling during injuries may be causally related to oxidative stress. These observations suggest that coupling in glial networks may be functionally important in determining neuronal vulnerability to oxidative injuries.
MRI diffusion tensor tracking of a new amygdalo‐fusiform and hippocampo‐fusiform pathway system in humans

To use MRI diffusion‐tensor tracking (DTT) to test for the presence of unknown neuronal fiber pathways interconnecting the mid‐fusiform cortex and anteromedial temporal lobe in humans. Such pathways are hypothesized to exist because these regions coactivate in functional MRI (fMRI) studies of emotion‐valued faces and words, suggesting a functional link that could be mediated by neuronal connections.
Teenage mothers' anger over twelve years: partner conflict, partner transitions and children's anger.

BACKGROUND This study examined the effects of maternal anger, partner transitions and partner conflict on later oppositional and angry behavior of the children of teenage mothers. METHODS One hundred and twenty-one teenage women were interviewed prior to the birth of the baby and at 3 points subsequently, when children were newborn, 7 years old and 12 years old. Child and teacher reports of children's oppositional behavior were obtained. RESULTS Women who showed higher levels of anger at Time 1 experienced more conflict with partners and more partner transitions over the next 12 years than women with lower levels of anger. Partner conflict was a stronger predictor of children's oppositional and angry behavior than partner transitions. Maternal anger at Time 1 was associated with maternal anger at Time 4 but neither predicted children's oppositional behavior at Time 4. CONCLUSION There was support for the theoretical model that suggested that the personality characteristics of teenaged mothers confer some of their risk to children through children's exposure to the mothers' problematic partner relationships.
Unique Structural and Functional Properties of the ATP-binding Domain of Atypical Protein Kinase C-ι*

Atypical protein kinase C-ι (aPKCι) plays an important role in mitogenic signaling, actin cytoskeleton organization, and cell survival. Apart from the differences in the regulatory domain, the catalytic domain of aPKCι differs considerably from other known kinases, because it contains a modification within the glycine-rich loop motif (GXGXXG) that is found in the nucleotide-binding fold of virtually all nucleotide-binding proteins including PKCs, Ras, adenylate kinase, and the mitochondrial F1-ATPase. We have used site-directed mutagenesis and kinetic analysis to investigate whether these sequence differences affect the nucleotide binding properties and catalytic activity of aPKCι. When lysine 274, a residue essential for ATP binding and activity conserved in most protein kinases, was replaced by arginine (K274R mutant), aPKCι retained its normal kinase activity. This is in sharp contrast to results published for any other PKC or even distantly related kinases like phosphoinositide 3-kinase γ, where the same mutation completely abrogated the kinase activity. Furthermore, the sensitivity of aPKCι for inhibition by GF109203X, a substance acting on the ATP-binding site, was not altered in the K274R mutant. In contrast, replacement of Lys-274 by tryptophan (K274W) completely abolished the kinase activity of PKCι. In accordance with results obtained with other kinase-defective PKC mutants, in cultured cells aPKCι-K274W acted in a dominant negative fashion on signal transduction pathways involving endogenous aPKCι, whereas the effect of the catalytically active K274R mutant was identical to the wild type enzyme. In summary, aPKCι differs from classical and novel PKCs also in the catalytic domain. This information could be of significant value for the development of specific inhibitors of aPKCι as a key factor in central signaling pathways.
Commissioning and Clinical Implementation of a Sliding Gantry CT Scanner Installed in an Existing Treatment Room and Early Clinical Experience for Precise Tumor Localization

The primary objective of the present study is to demonstrate that a unique computed tomography (CT)-linear accelerator combination can be used to reduce uncertainties caused by organ motion and setup inaccuracy. The acceptance, commissioning, and clinical implementation of a sliding gantry CT scanner installed in an existing linear accelerator room are reported in this paper. A Siemens CT scanner was installed directly opposite to an existing accelerator. The scanner is movable on a pair of horizontal rails mounted parallel to the longitudinal axis of the treatment couch replaced with a carbon fiber tabletop. Acceptance and commissioning of the CT scanner were verified with phantom studies. For clinical implementation, quality assurance (QA) procedures have been instituted to ensure the integrity of the CT gantry axis alignment and the accuracy of its movement using a phantom designed in house. A clinical example employing the CT-Linac combination to correct the isocenter positioning caused by organ motion and setup inaccuracy was presented for a prostate irradiation. Dose calculations were performed to study the effects on tumor coverage without the adjustments of the isocenter. A summary of the isocenter adjustments for the first 30 patients is also presented. The geometric accuracy of the CT scanner is ≤1 mm. An isocenter deviation of ≥2 mm from the original plan can be detected. For the clinical example of a prostate patient, the average movement of the prostate gland was found to be ∼3mm in the anterior-posterior (AP/PA) direction and 5 mm in the cephalic-caudal direction. Variations in the isocenter position may result in underdosage of the PTV if correction is not made for the change in the isocenter position. Our experience with the first 30 patients indicates that while the left-right adjustment of the isocenter is minimal, in the AP/PA direction, about 33% of treatments required an adjustment of 3–5 mm, and about 18% required a 5.1-mm to 10-mm adjustment. In the caudal-cephalic direction, about 26% required an adjustment of 3–5 mm, and 8% required a 5.1-mm to 10-mm adjustment. Retrofitting a CT scanner in an existing linear accelerator room requires careful planning and well-coordinated efforts from all personnel involved. Special QA procedures are needed to ensure the mechanical integrity and imaging accuracy of the CT scanner. A CT scan of the patient prior to irradiation provides valuable information on organ motion. Any deviations from treatment plan can be corrected before dose delivery. Significant deviation from the planning isocenter may occur due to daily variations in the rectal filling. The CT-Linac combination has significant implications for the treatment of prostate cancer.
Acupuncture for benign prostatic hyperplasia: a systematic review protocol

Introduction Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate commonly encountered in older men. BPH has been treated with acupuncture inside and outside China, but its effects are uncertain. This review aims to assess the efficacy and safety of acupuncture therapy for BPH. Methods and analysis Seven databases will be searched from their inception: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Chinese Biomedical Database, the China National Knowledge Infrastructure, the VIP Database and Wanfang Database. Randomised controlled clinical trials using acupuncture to treat BPH will be included. Outcome measures included urological symptom scores, urodynamic measures and quality-of-life scales. Adverse events will be assessed and reported for safety evaluation. Study selection and data extraction will be performed by two independent reviewers. Quality assessment (assessment of risk of bias) and data synthesis will be implemented using Review Manager (RevMan) software (V.5.2.3). Ethics and dissemination Ethical approval is not necessary because this systematic review will not include specific patient data. Updates will be conducted if there is enough new evidence that may cause any change in review conclusions. Trial registration number PROSPERO CRD42014013645.
Burn-out bij Belgische arts-specialisten in opleiding : exploratie van het relatieve belang van werkorganisatorische risicofactoren

Burn-out is een vaak voorkomend syndroom bij professionele hulpverleners en met name arts-specialisten in opleiding zijn een kwetsbare groep. Preventieve maatregelen worden tot heden voornamelijk toegespitst op het individu, terwijl werk-organisatorische maatregelen nog vaak achterwege blijven. Deze studie bevroeg arts-specialisten in opleiding welke spanningsbronnen (met zowel een positieve als negatieve invloed) zij ervaren gedurende hun assistentenperiode. Dertien thema’s werden ontleed waarvan de hoge werkdruk, het belang van professionele ontwikkeling en het belang van gedegen feedback proportioneel de belangrijkste bleken te zijn. Bevordering van het welzijn van arts-specialisten in opleiding gaat verder dan het optimaliseren van de arbeidsduur. Onze resultaten suggereren om middelen vrij te maken voor het verder versterken van de coaching-vaardigheden van supervisors (feedback training, versterken van sociale steun, erkenning geven). Het vinden en monitoren van de juiste balans tussen autonomie en begeleiding is cruciaal om het aantal succeservaringen te maximaliseren. Bovendien zou een betere afstemming tussen de stage en de studies het welzijn positief bevorderen.
Expression and Characterization of Cynomolgus Monkey Cytochrome CYP3A4 in a Novel Human Embryonic Kidney Cell–Based Mammalian System

Cynomolgus monkeys are a commonly used species in preclinical drug discovery, and have high genetic similarity to humans, especially for the drug-metabolizing cytochrome P450s. However, species differences are frequently observed in the metabolism of drugs between cynomolgus monkeys and humans, and delineating these differences requires expressed CYPs. Toward this end, cynomolgus monkey CYP3A4 (c3A4) was cloned and expressed in a novel human embryonic kidney 293-6E cell suspension system. Following the preparation of microsomes, the kinetic profiles of five known human CYP3A4 (h3A4) substrates (midazolam, testosterone, terfenadine, nifedipine, and triazolam) were determined. All five substrates were found to be good substrates of c3A4, although some differences were observed in the Km values. Overall, the data suggest a strong substrate similarity between c3A4 and h3A4. Additionally, c3A4 exhibited no activity against non-h3A4 probe substrates, except for a known human CYP2D6 substrate (bufuralol), which suggests potential metabolism of human cytochrome CYP2D6-substrates by c3A4. Ketoconazole and troleandomycin showed similar inhibitory potencies toward c3A4 and h3A4, whereas non-h3A4 inhibitors did not inhibit c3A4 activity. The availability of a c3A4 preparation, in conjunction with commercially available monkey liver microsomes, will support further characterization of the cynomolgus monkey as a model to assess CYP3A-dependent clearance and drug-drug interactions.
Mycobacteria exploit nitric oxide‐induced transformation of macrophages into permissive giant cells

Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so‐called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double‐edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO‐induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria‐infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state.
In Vivo Efficacy of a Novel Oxazolidinone Compound in Two Mouse Models of Infection

ABSTRACT A novel oxazolidinone, AM 7359, was evaluated in two mouse models of Staphylococcus aureus infection. AM 7359 and linezolid were equally efficacious in a methicillin-susceptible S. aureus organ burden model and a methicillin-resistant S. aureus localized infection model. However, AM 7359 was eightfold more efficacious than linezolid against a linezolid- and methicillin-resistant S. aureus strain in this localized (thigh) infection model.
General Analysis and Design Guideline for a Battery Buffer System With DC/DC Converter and EDLC for Electric Vehicles and its Influence on Efficiency

In this paper, the general design of a battery buffer system (BBS) consisting of a dc/dc converter and electric double layer capacitors for an electric vehicle is presented. This is intended to save the regenerative braking energy and to support the battery during acceleration. The design of a multiphase converter in interleaved operation with nonideal coupled inductors is stated to minimize volume and power losses while maintaining given current ripple limitations. A reduced sensor current-sharing control method is developed and its correct choice of the sensor position is explained. The peak efficiency of the designed and built converter can be measured to nearly 99%. The corresponding BBS is implemented in a lead-acid battery powered electric lift truck propulsion system. The system operation with and without the BBS is compared to examine the behavior and the overall efficiency. It can be shown that the traction battery stress can be strictly reduced as well as the temperature rise in the battery. Furthermore, the efficiency can be increased in the range of 5-6%. The battery's lifetime improvement is estimated by means of the difference in the temperature rise to approximately 20%.
A framework for identification and classification of outsourcing related organizational risks in a pharmaceutical supply chain

Outsourcing supply chain activities is not simple. Yet, it allows organizations to strategically use outside vendors to perform activities that traditionally have been internal functions such as information systems, value buying and logistics in order to achieve efficiently, a higher level of product availability. The outsourcing strategy is considered, however, as a major change that may impact heavily the business competitiveness and future. In this context, organizations that are considering strategic outsourcing of supply chain activities must manage and control carefully the related risk factors in order to meet the sourcing objectives. This paper introduces a framework inspired from the Enterprise Risk Management (ERM) approach and aims to identify and classify outsourcing related organizational risks. This framework was operationalized for the case of the pharmaceutical supply chain in the public sector in Morocco.
[Relationship between pathological alterations of spermatogenic impairment and serum inhibin B concentration in patients with azoospermia].

OBJECTIVE To investigate the relationship between pathological alterations of spermatogenic impairment in seminiferous tubules and serum inhibin B concentration in patients with azoospermia and to verify the significance of INH B in evaluating spermatogenesis. METHODS Eighty-three cases of azoospermia underwent testicular biopsy for the purpose of diagnosis. In accordance with the pathological alterations of spermatogenesis in seminiferous tubules, the samples were divided into four groups: Sertoli cell-only syndrome (n = 21); hypospermatogenesis (n = 20); maturation arrest (n = 24) and almost normal spermatogenesis (n = 18). Serum INHB and FSH, LH, T concentrations were tested before testicular biopsy for each patient respectively. RESULTS The INHB levels were (20. 85 +/- 18.78) pg/ml, (67.25 +/- 40.98) pg/ml, (73.63 +/- 25.54) pg/ml and (149.48 +/- 27.92) pg/ml in the above four groups, respectively. There was no significant statistical difference in the level of serum INH B between maturation arrest and hypospermatogenesis groups (P > 0.05), and there was a very significant difference in almost normal spermatogenesis group and the other three groups, respectively (P < 0.001). There was no significant difference in the concentration of serum FSH when maturation arrest group compared with spermatogenesis group (P > 0.05), whereas between the other two groups and between each of them and maturation arrest or almost normal spermatogenesis there was a very significant difference in the level of serum FSH (P < 0.05); The concentrations of LH and T were not significantly different among the four groups (P > 0.05). CONCLUSION Serum INHB concentration was decreased when spermatogenesis got impaired. It dropped the most markedly in Sertoli cell-only syndrome group. INH B reflects directly the spermatogenic function in seminiferous tubules of the testis. Therefore, it could be considered valuable for spermatogenesis and potential fertility in patients with azoospermia.
N‐acetyltransferase polymorphisms are associated with risk of lymphoma subtypes

Genes encoding for arylamine N‐acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non‐Hodgkin lymphoma (NHL). We tested functional haplotype‐based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B‐NHL, DLBCL, FL, CLL, and other B‐NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8‐fold excess risk (95% CI 1.5–5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd.
Genetic variation between and within Triodontophorus brevicauda and Triodontophorus nipponicus revealed by analyses of mtDNA and rDNA gene sequences

Abstract Triodontophorus spp. parasitizes the large intestine of equine, causing strongylid diseases. The present study assessed genetic variation in five gene regions within and between Triodontophorus brevicauda and Triodontophorus nipponicus from Heilongjiang Province and the Inner Mongolia Autonomous region. The five gene markers were three mitochondrial (mt) genes, cytochrome c oxidase subunit I (cox1), NADH dehydrogenase subunit 5 (nad5), cytochrome b (cytb); and two ribosomal RNA genes, the internal transcribed spacer 1 (ITS1) and the internal transcribed spacer 2 (ITS2). Partial (p) sequences of cox1, nad5, cytb and the complete ITS rDNA region were PCR amplified from individual nematodes, and the amplicons were subjected to sequencing in both directions. The size of the three mt genes is identical in both species: 761 bp (p cox1), 505 bp (pnad5) and 562 bp (pcytb); the length of the two ribosomal genes is different: 376 bp and 370 bp (ITS1), and 333 bp and 322 bp (ITS2), respectively. Intraspecific variation between T. brevicauda and T. nipponicus was 0–1.5% and 0–1.1% for pcox1, 0–2.0% and 0–2.0% for pnad5, 0–1.4% and 0–2.2% for pcytb, 0–0.8% and 0–1.1% for ITS1 and 0–0.9% and 0–2.2% for ITS2. Interspecific variation within the nematodes was 13.5–14.3% for pcox1, 15.5–18.7% for pnad5, 16.7–18.6% for pcytb, 11.5–13.1% for ITS1 and 16.0–18.4% for ITS2. Phylogenetic analyses based on the combined mt gene sequences, as well as with the ITS sequences, show each species forming a monophyletic group of individuals. However, samples of different species from the same geographical origin did not always cluster together. These results provide valuable information for further studies of systematics and population genetics of the genus Triodontophorus.
Social support, social conflict, and adjustment among adolescents with cancer.

OBJECTIVE Evaluate support and conflict in close relationships of adolescents in active medical treatment for cancer. Family and friend perceptions of supportive and conflictual behaviors were examined in relation to psychological distress, taking into account the impact of functional impairment induced by the illness. METHODS Using self-report questionnaires, 50 adolescents between the ages of 12 and 20 years rated the frequency of supportive and conflictual interactions with parents, siblings and best friends. RESULTS Results indicated that perceived maternal conflict was associated with psychological distress. Conflict with fathers, siblings, and best friends was not associated with distress. Supportive aspects of close relationships did not predict psychological distress. The amount of physical impairment accounted for the most variance in distress, contributing between 35% and 38% of the variance. CONCLUSION Results suggest that mother-adolescent conflict would be an appropriate target for psychosocial interventions.