Miracle-dz/UniFAR-FTUs huggingface dataset:
Biophysical properties of Nav1.8/Nav1.2 chimeras and inhibition by µO‐conotoxin MrVIB

BACKGROUND AND PURPOSE Voltage‐gated sodium channels are expressed primarily in excitable cells and play a pivotal role in the initiation and propagation of action potentials. Nine subtypes of the pore‐forming α‐subunit have been identified, each with a distinct tissue distribution, biophysical properties and sensitivity to tetrodotoxin (TTX). Nav1.8, a TTX‐resistant (TTX‐R) subtype, is selectively expressed in sensory neurons and plays a pathophysiological role in neuropathic pain. In comparison with TTX‐sensitive (TTX‐S) Navα‐subtypes in neurons, Nav1.8 is most strongly inhibited by the µO‐conotoxin MrVIB from Conus marmoreus. To determine which domain confers Nav1.8 α‐subunit its biophysical properties and MrVIB binding, we constructed various chimeric channels incorporating sequence from Nav1.8 and the TTX‐S Nav1.2 using a domain exchange strategy.
Emotional Functioning and School Contentment in Adolescent Survivors of Acute Myeloid Leukemia, Infratentorial Astrocytoma, and Wilms Tumor.

Purpose: Cancer in childhood may disrupt normal developmental processes and cause psychosocial problems in adolescent survivors of childhood cancers (ACCSs). Previous studies report inconsistent findings. Study aims were to assess subjective well-being (SWB), psychological distress, and school contentment in survivors of three dissimilar childhood cancers. Patients and methods: Nordic patients treated for acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in childhood from 1985 to 2001, aged ≥1 year at diagnosis, and aged 13-18 years at the time of study were eligible for this questionnaire-based survey that included items on SWB, psychological distress, school contentment, self-esteem, and personality traits; 65% (151/231) responded. An age-equivalent group from a Norwegian health survey (n=7910) served as controls. Results: The median age of ACCSs was 16 years; 52% were males. ACCSs reported better SWB (p=0.004) and self-esteem (p<0.001). They had fewer social problems in school (p=0.004) and their school contentment tended to be higher than controls. SWB and school contentment were positively influenced by self-esteem. However, ACCSs reported higher levels of psychological distress (p=0.002), mostly attributable to general worrying. No significant differences in outcomes were found across diagnoses, and time since diagnosis did not significantly affect the results. Conclusion: The overall emotional functioning of ACCSs was good, possibly due to changes in their perception of well-being after having survived a life-threatening disease. However, they seemed more worried than their peers. This may cause an additional strain at a vulnerable period in life.
Neural Correlates of Sad Feelings in Schizophrenia with and without Blunted Affect

Objective: There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts. Methods: We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level–dependent functional magnetic resonance imaging. Results: A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA–patients at a 0.05 level (P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA–patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal pole in the BA–group; and hippocampus, cerebellum, anterior temporal pole, and midbrain in the BA+ group. Conclusions: We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect.
In vitro immunomodulatory activity, cytotoxicity and chemistry of some central European polypores

Abstract Context Some mushrooms of the order Polyporales are known for their immunomodulatory actions. Objective The objective of this study is to evaluate the in vitro phagocytic and cytotoxic effects of extracts from polyporales native to Central Europe. Materials and methods The effects of ethanol extracts from 27 polypore species on opsonized zymosan-induced phagocytosis of isolated human neutrophils were tested by a chemiluminescence method. Colon epithelial cell lines, Caco-2 and HT-29, were used for cytotoxicity assays, and extracts were chemically characterized in terms of total phenolic and β-glucan content. Results We observed phagocytosis or respiratory burst enhancing activity in 17 extracts, of which five species, namely Aurantiporus fissilis (Berk. & M.A. Curtis) H. Jahn ex Ryvarden, Trametes gibbosa (Pers.) Fr. , Piptoporus betulinus (Bull.) P. Karst, Neolentinus lepideus (Fr.) Redhead & Ginns, Polyporus squamosus (Huds.) Fr. , significantly increased phagocytosis in granulocytes by 205, 181, 158, 155 and 141%, respectively. The β-glucan content of the three most potent extracts was 58, 42 and 74 mg/g, respectively, and the polyphenol content was 155.6, 133.5 and 155.2 μmol of gallic acid equivalent/g, respectively. Some extracts showed cytotoxic activity, with higher cytotoxicity in Caco-2 than in HT-29 cells. Pycnoporus cinnabarinus (Jacq.) P. Karst. extract was cytotoxic to both cell lines, with IC50 values of 81 and 31 μg/mL, respectively. Discussion and conclusion The most promising extracts were from N. lepideus and Polyporus squamosus, which are edible species and may be considered safe. Our findings support their use as culinary preparations or food supplements for various immunological gut disorders.
Contact mechanics analysis of metal-on-metal hip resurfacing prostheses

Abstract Finite-element method was employed to study the contact mechanics in metal-on-metal hip resurfacing prostheses, with particular reference to the effects of bone quality, the fixation condition between the acetabular cup and bone, and the clearance between the femoral head and the acetabular cup. Simple finite-element bone models were developed to simulate the contact between the articulating surfaces of the femoral head and the acetabular cup. The stresses within the bone structure were also studied. It was shown that a decrease in the clearance between the acetabular cup and femoral head had the largest effect on reducing the predicted contact-pressure distribution among all the factors considered in this study. It was found that as the clearance was reduced, the influence of the underlying materials, such as bone and cement, became increasingly important. Stress shielding was determined to occur in the bone tissue surrounding the hip resurfacing prosthesis considered in this study. However, the stress-shielding effects predicted were less than those observed in conventional total hip replacements. Both the effects of bone quality (reduction in elastic modulus) and the fixation condition between the cup and the bone were found to have a negligible effect on the predicted contact mechanics at the bearing surface. The loading was found to have a relatively small effect on the predicted maximum contact pressure at the bearing surface; this was attributed to an increase in contact area as the load was increased.
Intra‐individual variations in acute and cumulative skin irritation responses

It is well‐known that humans show a wide range of variation in skin reactivity to irritant chemicals. This has been established through population studies, through the examination of inter‐subject variability, and (to a limited extent) through studies of skin site variation in response within subjects. However, simple response variability within individual test subjects has not been examined as carefully, and this has implications for our ability to predict irritant reactivity. Some key questions are: (i) how consistently do human beings respond, even within a given study, to different equally irritating chemicals, or to the same chemical when comparing different concentrations or durations of exposure, and, (ii) Do individual test subjects’ responses to one chemical (or exposure scenario) correlate with their responses to another? To examine these questions in some detail, we reexamined individual study subjects’ responses from earlier published studies involving both acute and cumulative irritation patch test protocols. Acute irritation responses were compared across chemicals with similar irritation profiles. Cumulative irritation responses were compared across different concentrations of the anionic surfactant, sodium dodecyl sulfate (SDS). Acute (high concentration) and cumulative (low concentration) patch test responses to SDS were also compared. The analysis showed that, as might be expected, response correlations were greatest within test types, either when comparing chemicals of similar overall irritancy, or when comparing similar concentrations of a single chemical. However, individually divergent responses were also frequent, reinforcing the conclusion that a given individual’s response to one chemical or exposure condition does not always predict their response to another. This has important ramifications for other questions related to population differences in skin reactivity.
Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNγ and TNFα were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.
Examining the Influence of Rapport between Players and Dealers on Customer Satisfaction, Revisit Intentions, and Word-of-Mouth in the Casino Industry: The Moderating Role of Gender

ABSTRACT This study explores the role of rapport between players and dealers in the casino industry. More specifically, based on a literature review, it was proposed that (1) rapport positively affects three outcome variables: customer satisfaction, revisit intentions, and word-of-mouth; (2) customer satisfaction has a positive influence on revisit intentions and word-of-mouth; and (3) gender plays a moderating role in this process. Based on the proposed hypotheses, a conceptual model was developed and tested using empirical data from 227 casino table players. Data analysis results showed that rapport is an important determinant of customer satisfaction, revisit intentions, and word-of-mouth. In addition, it was revealed that customer satisfaction bears a significant impact on revisit intentions and word-of-mouth. Lastly, gender has key moderating functions in the relationship between (1) rapport and customer satisfaction and (2) rapport and revisit intentions. The possible interpretations and managerial implications of these findings are provided in the last part of the article.
Fear of cancer recurrence and unmet needs among breast cancer survivors in the first five years. A cross-sectional study

Abstract Background: It is unclear to which degree the services available after end of treatment are sufficient to meet the needs of women treated for breast cancer. The aim of the present study was to identify patient-reported supportive care needs and the prevalence of fear of cancer recurrence (FCR) following end of treatment in women treated for breast cancer. Material and methods: Using a cross-sectional design, women treated for breast cancer (n = 155; mean age 63) completed questionnaires concerning supportive care needs and FCR. Inclusion criteria were: ≥18 years of age and treated for primary breast cancer at Aarhus University Hospital, Aarhus, Denmark and between three months and five years after diagnosis. Associations between demographic characteristics, clinical factors, side effects, late effects and the two dependent variables, unmet needs (examined with linear regression model), and FCR (examined with logistic regression model) were analyzed. Results: The response rate was 79.9%. Almost all (82.6%) women reported at least one unmet need (mean number 9.3; range 0–34). More than half (59.3%) of the unmet needs were rated as strong unmet needs. The most frequent unmet needs were concerned with doctors collaborate to coordinate care; the need for having ongoing dialog with healthcare providers to receive available local health care services, understandable and up-to-date information, to manage side effects and feeling reassured that the best medical care are given. Having unmet needs were associated with young age, short time since primary surgery, and having clinical FCR. FCR was reported by 54.8% of the women and was associated with short time since primary surgery, having chemotherapy, having unmet needs, and moderate to severe muscle and joint pain and fatigue. Conclusions: Breast cancer survivors experience substantial unmet needs years after end of treatment, particularly among younger women and women having clinical FCR. Furthermore, FCR is frequent among women, particularly when closer in time to primary surgery.
Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy

To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [<25% reduction on the Montgomery–Åsberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ⩽10. Rates were examined using analysis of covariance and Cochran–Mantel–Haenszel tests. Kaplan–Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (−10.3 vs. −6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.
A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end‐stage liver disease system

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end‐stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)‐Child‐Turcotte‐Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC‐MELD era, 138 patients, 29.7% with HCC). In the HCC‐MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS‐CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS‐CTP era for patients with HCC (P = 0.02). At the end of the HCC‐MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial‐final native MELD scores were 17.3‐23.1, 15.5‐15.6, and 12.8‐14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial‐final: 15.1‐15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC. Liver Transpl 13:857–866, 2007. © 2007 AASLD.
Characterization and purification of bile salt hydrolase from Lactobacillus sp. strain 100-100

We have characterized and purified the bile salt hydrolase from Lactobacillus sp. strain 100-100. Bile salt hydrolase from cells of the strain was purified with column and high-performance liquid chromatography. The activity was assayed in whole cells and cell-free extracts with either a radiochemical assay involving [14C]taurocholic acid or a nonradioactive assay involving trinitrobenzene sulfonate. The activity was detectable only in stationary-phase cells. Within 20 min after conjugated bile acids were added to stationary-phase cultures of strain 100-100, the activity in whole cells increased to levels three- to fivefold higher than in cells from cultures grown in medium free of bile salts. In cell-free extracts, however, the activity was about equal, 1.41 and 1.53 mumol/min per mg of protein, respectively, whether or not the cells have been grown with bile salts present. When supernatant solutions from cultures grown in medium containing taurocholic acid were used to suspend cells grown in medium free of the bile salt, the bile salt hydrolase activity detected in whole cells increased two- to threefold. Two forms of the hydrolase were purified from the cells and designated hydrolases A and B. They eluted from anion-exchange high-performance liquid chromatography in two sets of fractions, A at 0.15 M NaCl and B at 0.18 M NaCl. Their apparent molecular weights in nondenaturing polyacrylamide gel electrophoresis were 115,000 and 105,000, respectively. However, discrepancies existed in the apparent molecular weights and number of peptides detected in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the two forms. Both had similar substrate specificities, highest on taurodeoxycholic and glycocholic acid, and pH optima between 3.8 and 4.5. The kinetic properties were also similar, with Vmaxs of 17 and 53 micromoles/min per mg of protein and Kms of 0.76 and 0.95 mM taurocholic acid for A and B, respectively. Therefore, whether the enzyme exists in two forms in the cells remains to be determined.
Cocaine treatment increases extracellular cholecystokinin (CCK) in the nucleus accumbens shell of awake, freely moving rats, an effect that is enhanced in rats that are behaviorally sensitized to cocaine

Cholecystokinin (CCK) is co‐localized with dopamine, is known to modulate dopamine neurotransmission and is involved in behavioral sensitization to psychostimulants. To better understand its role, CCK was measured by microdialysis in the nucleus accumbens (NAC) shell in response to cocaine in drug‐naive rats and in rats that are behaviorally sensitized to cocaine. Basal extracellular levels of CCK in drug‐naive rats were 0.17 pg/20 min fraction, while in cocaine‐sensitized rats, they were significantly higher (0.56 pg). Treating drug‐naive rats with cocaine caused a significant increase in CCK to 0.58 pg. Cocaine treatment of cocaine‐sensitized rats increased CCK to 0.98. When analyzed as a function of time after cocaine treatment, these increases were sustained and were significantly different from CCK levels of saline‐treated rats. In cocaine‐sensitized rats, CCK levels following cocaine treatment were also significantly higher than levels in drug‐naive animals receiving a single injection of cocaine. These results provide evidence for an activation of the mesolimbic and/or cerebral cortical CCK system in response to repeated cocaine administration. These results provide a neurochemical basis for an important role of CCK (via modulation of dopamine neurotransmission) in expression of cocaine sensitization.