Miracle-dz/UniFAR-FTUs huggingface dataset:
Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9–39)

Abstract Glicentin and glucagon‐like peptide‐1 (7–36) amide (GLP‐1) are gut hormones released during digestion. Glicentin and GLP‐1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP‐1, and if their motility is dependent upon these digestive hormones. Methods: Twenty‐two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed. Results: Glicentin caused a dose‐related contraction of SMC, when GLP‐1 determined a contraction of weak amplitude. Exendin‐(9–39), described as a GLP‐1 receptor antagonist, inhibited contraction due to glicentin or GLP‐1. In contrast, on antral SMC from rabbit, GLP‐1 exerts neither relaxation nor contraction; however, exendin‐(9–39) dose dependently reduced the contractile activity of glicentin [glicentin EC50 = 5 pM, exendin‐(9–39) pA2 = −9.36]. Conclusions: The circular muscle from the human colon is a target tissue for glicentin and GLP‐1. Whereas glicentin is a long‐life digestive hormone which would contribute to segmental contraction, the biological activity of GLP‐1 remains unknown on this tissue. On the digestive smooth muscle, exendin‐(9–39) behaved as an antagonist for two members of the glucagon‐receptor family, GLP‐1 and glicentin.
Adaptive response of human skeletal muscle to simulated hypergravity condition.

The mechanical behaviour of leg extensor muscles of five international-level athletes was evaluated during 13 months training period. Drop jumps, average mechanical power during 15 S continuous jump, and vertical jumps performed with and without extra weights were used to measure explosive power characteristics. The data recorded in vertical jumps was utilized for construction of force-velocity relationship (F-V curve). The athletes did not show improvement in any of the variables studied after 12 months of intensive systematic training programme. It was assumed that the subjects already had reached their upper limit of performance. However, after that the athletes underwent a simulated 3 weeks high-gravity period. The hypergravitational condition was created by wearing a special vest filled with extra loads (11% of BW). The vest was used from morning to evening. No changes in the ordinary training programme were allowed. After the simulated high-gravity conditioning period significant improvement in almost all the variables studied was observed (P less than 0.05-0.001). Vertical jump performance was enhanced from 44.3 to 54.9 cm. The F-V curve remained stable all year but after hypergravity period shifted markedly to the right. The drastic improvement was attributed to be caused by a fast adaptation to the new functional requirements (I.I g). Therefore, once the biological adaptation occurred the mechanical behaviour of the athlete's leg extensor muscle was similar to that which could be experienced in a field at low gravity condition (0.9 g). Adaptive response to the hypergravity conditioning was speculated to occur mainly at neurogenic level and less in myogenic component.
Assessing the Acceptability and Usability of an Interactive Serious Game in Aiding Treatment Decisions for Patients with Localized Prostate Cancer

Background Men diagnosed with localized prostate cancer face a potentially life-altering treatment decision that can be overwhelming. Enhancing patient knowledge through education can significantly reduce feelings of uncertainty while simultaneously increasing confidence in decision making. Serious games have been shown in other populations to increase health knowledge and assist with the health decision-making process. We developed an interactive serious game, Time After Time, which translates evidence-based treatment outcome data into an accessible and understandable format that men can utilize in their prostate cancer treatment decision-making process. The game specifically aims to raise men’s awareness and understanding of the impact of health-related quality of life issues associated with the major treatment options and to enrich their conversations with their health care providers. Objective This study determined the acceptability and usability of the alpha version of Time After Time, an interactive decision aid for men diagnosed with localized prostate cancer, in order to inform future iterations of the serious game. Methods The study employed a mixed methods approach to assess the acceptability and usability of the Time After Time serious game using qualitative focus groups and a quantitative Likert scale survey. Results A total of 13 men who had already completed treatment for localized prostate cancer completed the survey and participated in focus group meetings. The majority of the study participants rated Time After Time as an appropriate decision tool for localized prostate cancer and verified that it meets its goals of increasing focus on side effects and generating questions for the patient’s health care team. However, participants also expressed concerns about game usability and the diversity of information covered regarding treatment options and potential treatment outcomes. Conclusions Serious games are a promising approach to health education and decision support for older men. Participants were receptive to the idea of a serious game as a decision aid in localized prostate cancer. However, usability issues are a major concern for this demographic, as is clarity and transparency of data sources.
Structure‐Activity Relationships of Conformationally Constrained Peptide Analogues of Loop 2 of Brain‐Derived Neurotrophic Factor

Abstract: Brain‐derived neurotrophic factor (BDNF) promotes the survival of various neuronal populations and thus shows potential in the treatment of neurodegenerative disease. However, BDNF is not pharmacokinetically optimal for use as a therapeutic agent. As a step toward the development of low‐molecular‐weight BDNF‐like drugs, we have designed a series of small, conformationally constrained peptides of various sizes using the three‐dimensional structure of BDNF derived by homology modeling as a template. When tested in cultures of embryonic chick sensory neurons the peptides produced concentration‐dependent inhibition of BDNF‐mediated neuronal survival and caused both a rightward shift and depression of the maximum of the BDNF concentration‐response curve. The compounds had no effect on the survival response to nerve growth factor and were without intrinsic trophic or toxic effects when added to cultures alone. With the aid of pharmacodynamic simulations we demonstrated that the inhibitory activity of the active peptides is consistent with them acting as competitive antagonists of BDNF for its high‐affinity receptor, trkB. An alanine scan of the largest peptide identified several residues important in mediating the inhibitory action of the peptides. We intend to use the data from these studies to develop small peptidic BDNF‐like agonists.
Institutional perspectives on post-socialist transformation with particular reference to township and village enterprises in China.

The orthodox transition literature, that has dominated the debate on Eastern Europe, argues that well-defined property rights are a precondition for successful transition in post-socialist countries. As a result, most of this literature has treated the success of China's economic reforms as an enigma. The dilemma for "transition economists" is that the driving force behind China's high rate of economic growth has been the outstanding performance of its township and village enterprises (T.V.Es). Yet, in most cases, it is not clear who owns the T.V. E - the local residents or the township and village government. This thesis puts forward two main arguments. The first is that the success which T.V. Es have had can be explained through drawing on different notions of the division of labour. The second is that T.V. Es are a specific example of a broader literature on regionalism and that their success suggests some wider lessons. These form the basis of an alternative vision for post-socialist transformation based on collective learning. The thesis suggests that there is a legitimate cognitive function for less than arms-length relationships in post-socialist economies as part of a more general pattern of institutionalised diversification.
Neurogenin2-d4Venus and Gadd45g-d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain

To achieve highly sensitive and comprehensive assessment of the morphology and dynamics of cells committed to the neuronal lineage in mammalian brain primordia, we generated two transgenic mouse lines expressing a destabilized (d4) Venus controlled by regulatory elements of the Neurogenin2 (Neurog2) or Gadd45g gene. In mid‐embryonic neocortical walls, expression of Neurog2‐d4Venus mostly overlapped with that of Neurog2 protein, with a slightly (1 h) delayed onset. Although Neurog2‐d4Venus and Gadd45g‐d4Venus mice exhibited very similar labeling patterns in the ventricular zone (VZ), in Gadd45g‐d4Venus mice cells could be visualized in more basal areas containing fully differentiated neurons, where Neurog2‐d4Venus fluorescence was absent. Time‐lapse monitoring revealed that most d4Venus+ cells in the VZ had processes extending to the apical surface; many of these cells eventually retracted their apical process and migrated basally to the subventricular zone, where neurons, as well as the intermediate neurogenic progenitors that undergo terminal neuron‐producing division, could be live‐monitored by d4Venus fluorescence. Some d4Venus+ VZ cells instead underwent nuclear migration to the apical surface, where they divided to generate two d4Venus+ daughter cells, suggesting that the symmetric terminal division that gives rise to neuron pairs at the apical surface can be reliably live‐monitored. Similar lineage‐committed cells were observed in other developing neural regions including retina, spinal cord, and cerebellum, as well as in regions of the peripheral nervous system such as dorsal root ganglia. These mouse lines will be useful for elucidating the cellular and molecular mechanisms underlying development of the mammalian nervous system.
Experimental exposure to methyl tertiary-butyl ether. I. Toxicokinetics in humans.

Methyl tertiary-butyl ether (MTBE) is widely used in gasoline as an oxygenate and octane enhancer. The aim of this study was to evaluate the uptake, distribution, metabolism, and elimination of MTBE in humans. Ten healthy male volunteers were exposed to MTBE vapor (5, 25, and 50 ppm) on three different occasions during 2 h of light physical exercise (50 W). MTBE and the metabolite tertiary-butyl alcohol (TBA) were monitored in exhaled air, blood, and urine. Blood and urine were collected at selected time intervals, during and up to 3 days after the exposure, and analyzed by head space gas chromatography. MTBE in exhaled air was collected with sorbent sample tubes and subsequently analyzed by gas chromatography. The respiratory uptake of MTBE was rather low (42-49%), and the respiratory exhalation was high (32-47%). A relatively low metabolic blood clearance (0.34-0.52 L/h/kg) was seen compared to many other solvents. The kinetic profile of MTBE in blood could be described by four phases, and the average half-lives were 1 min, 10 min, 1.5 h, and 19 h. The post-exposure decay curve of MTBE in urine was separated into two linear phases, with average half-lives of 20 min and 3 h. The average post-exposure half-lives of TBA in blood and urine were 10 and 8.2 h, respectively. The urinary excretion of MTBE and TBA was less than 1% of the absorbed dose, indicating further metabolism of TBA, other routes of metabolism, or excretion. The kinetics of MTBE and TBA were linear up to the highest exposure level of 50 ppm. We suggest that TBA in blood or urine is a more appropriate biological exposure marker for MTBE than the parent ether itself.
Ischemic Stroke and Its Risk Factors in a Registry-Based Large Cross-Sectional Diabetic Cohort in a Country Facing a Diabetes Epidemic

The main aim of this study is to determine the prevalence and risk factors of ischemic stroke among diabetic patients registered in the Saudi National Diabetes Registry (SNDR) database. A cross-sectional sample of 62,681 diabetic patients aged ≥25 years was used to calculate ischemic stroke prevalence and its risk factors. Univariate and multivariate logistic regression analyses were used to assess the roles of different risk factors. The prevalence of ischemic stroke was 4.42% and was higher in the older age group with longer diabetes duration. Poor glycemic control and the presence of chronic diabetes complications were associated with a high risk of ischemic stroke. History of smoking and type 2 diabetes were more frequent among stroke patients. Obesity significantly decreased the risk for ischemic stroke. Regression analysis for ischemic stroke risk factors proved that age ≥45 years, male gender, hypertension, coronary artery disease (CAD), diabetes duration ≥10 years, insulin use, and hyperlipidemia were significant independent risk factors for ischemic stroke. We conclude that ischemic stroke is prevalent among diabetic individuals, particularly among those with type 2 diabetes. Good glycemic, hypertension, and hyperlipidemia control, in addition to smoking cessation, are the cornerstones to achieve a significant reduction in ischemic stroke risk.
Effects of divided attention and word concreteness on correct recall and false memory reports

Lists of thematically related words were presented to participants with or without a concurrent task. In Experiments 1 and 2, respectively, English or Spanish word lists were either low or high in concreteness (concrete vs abstract words) and were presented, respectively, auditorily or visually for study. The addition of a concurrent visual or auditory task, respectively, substantially reduced correct recall and doubled the frequency of false memory reports (nonstudied critical or theme words). Divided attention was interpreted as having reduced the opportunity for participants to monitor successfully their elicitations of critical associates. Comparisons of concrete and abstract lists revealed significantly more recalls of false memories for abstract than concrete word lists. Comparisons between two levels of attention, two levels of word concreteness, and two presentation modalities failed to support the "more is less" effect by which enhanced correct recall is accompanied by increased frequencies of false memories.
Changes of islet size and islet size distribution resulting from protein-malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Bodyweight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (< or = 100 microns2) and a decrease in the population of large islets (> 20,000 microns2). In lean and obese rats fed low protein, beta-cell weight was significantly lower, beta cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancrease in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.
Long-Lasting Expression of HO-1 Delays Progression of Type I Diabetes in NOD Mice

Heme oxygenase-1 (HO-1) is crucial in regulating oxidative injury. The present study was designed to assess whether HO-1 upregulation by cobalt protoporphyrin IX (CoPP) moderates or prevents the diabetic state in non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes (T1D). HO-1 expression and HO activity were upregulated in the pancreas by the intermittent administration of CoPP. This was associated with decreases in blood glucose and pancreatic O2-, but increased pAKT and BcL-XL and cell survival. A considerable number of beta cells were preserved in the islets of CoPP-treated NOD mice, while none were found in untreated diabetic mice. The number of CD11c+ dendritic cells was decreased in the pancreas of CoPP-treated NOD mice (p
Nucleolar organizer regions in lymphomas

Using a silver staining technique, nucleolar organizer region‐associated proteins (Ag‐NORs) have been studied in paraffin sections of 90 non‐Hodgkin's lymphomas, five palatine tonsils and five ‘reactive’ lymph nodes. The method was readily applicable to these preparations and the Ag‐NORs were enumerated with ease. A significant difference was found between the numbers of Ag‐NORs in the nuclei of low‐grade lymphomas (from a mean of 1 to 1·5 per nucleus) and those of high‐grade lymphomas (a mean of 4·4 to 6·8 per nucleus). The Ag‐NOR regions were often observed in nuclei in areas where nucleoli themselves were not visible. It is suggested that this method, previously largely the province of the cytogeneticist, should find widespread applications in the field of tumour histopathology.
Biofilm-infected wounds in a dog.

CASE DESCRIPTION A 4-year-old spayed female Mastiff was evaluated for treatment of chronic nonhealing pressure wounds over both elbow regions resulting from attempts at hypertrophic callus excision. CLINICAL FINDINGS The wound bed granulation tissue was mottled red and yellow with hyperemic, rolled epithelial edges. The right wound communicated with a large fluid pocket along the thoracic wall. The dog had an inflammatory leukogram with a left shift. TREATMENT AND OUTCOME The wounds were debrided, and tissue specimens were collected for histologic evaluation, microbial culture, and bacterial identification by means of molecular diagnostic techniques. The left wound was closed immediately. Calcium alginate rope with silver was packed into the right wound. Vacuum-assisted closure was applied for 6 days. Debridement was repeated, and a thoracodorsal axial pattern flap was used to cover the wound. Systemic treatment with antimicrobials was initiated, and pressure over the elbow regions was relieved. Bacterial biofilms were identified histologically in tissue specimens from both wounds. Staphylococcus intermedius, Staphylococcus epidermidis, and Streptococcus canis were cultured and identified by 16S rRNA fragment sequencing. Pyrosequencing identified multiple bacterial species and no fungal organisms. Both wounds healed successfully. CLINICAL RELEVANCE Biofilms are implicated in infected orthopedic implants in veterinary patients; however, this is the first report of a bacterial biofilm in chronic wounds in a dog. In human wound care, extensive debridement is performed to disrupt the biofilm; a multimodal treatment approach is recommended to delay reformation and help clear the infection. In this case, biofilm reformation was prevented by systemic treatment with antimicrobials, by reducing local pressure on the wounds, and by wound closure.
Restoration by IL-15 of MHC Class I Antigen-Processing Machinery in Human Dendritic Cells Inhibited by Tumor-Derived Gangliosides1

We have recently reported that MHC class I Ag-processing machinery (APM) component expression in dendritic cells (DC) might be down-regulated by tumor cells. However, the tumor-derived factors responsible for inhibition of the APM component expression in DC generated in the tumor microenvironment as well as potential protective mechanism have not yet been investigated. In this article, we demonstrate that expression of several MHC class I APM components, including MB1 (β5), LMP2, LMP7, LMP10, and ERp57, is significantly down-regulated in human DC generated in the presence of primary oral squamous cell carcinoma cell lines or coincubated with purified gangliosides. Suppression of MHC class I APM component expression in DC generated in the presence of tumor cells was significantly attenuated by the inhibition of glucosyl transferase in tumor cells, suggesting that tumor-induced MHC class I APM component down-regulation in DC was mediated in part by oral squamous cell carcinoma-derived gangliosides. Furthermore, rIL-15 restored both tumor cell-induced and ganglioside-induced MHC class I APM component expression in DC, as well as their ability to present Ags to autologous Ag-specific T cells. These results demonstrate that IL-15 restores MHC class I APM component expression in DC down-regulated by tumor-derived gangliosides.
Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age < 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; Very-Old: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions. Young-Old AD and Very-Old AD groups were comparable in education, gender, dementia severity, and disease duration. Results showed that both AD groups achieved comparable raw scores on all the neuropsychological measures. However, when scores were standardized on the basis of performance of their respective NC groups (i.e., age-corrected z scores), Very-Old AD patients significantly outperformed Young-Old AD patients on tests of executive functions, visuospatial skills, and delayed memory. Furthermore, the relationship between age and memory and executive function deficits in AD was modified by APOE genotype. These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old. (JINS, 2003, 9, 783–795.)