Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Neuronal Degenerin/Epithelial Na+ Channels by the Multiple Sclerosis Drug 4-Aminopyridine*

Background: 4-AP treats the symptoms of MS because it inhibits Kv channels. Deg/ENaC channels contribute to the progression of MS. Results: 4-AP also inhibits Deg/ENaC channels. Conclusion: Effects on both Kv and Deg/ENaC channels should be considered when evaluating the actions of 4-AP. Significance: 4-AP may influence the symptoms and progression of MS because of inhibitory actions on Kv and Deg/ENaC channels, respectively. The voltage-gated K+ (Kv) channel blocker 4-aminopyridine (4-AP) is used to target symptoms of the neuroinflammatory disease multiple sclerosis (MS). By blocking Kv channels, 4-AP facilitates action potential conduction and neurotransmitter release in presynaptic neurons, lessening the effects of demyelination. Because they conduct inward Na+ and Ca2+ currents that contribute to axonal degeneration in response to inflammatory conditions, acid-sensing ion channels (ASICs) contribute to the pathology of MS. Consequently, ASICs are emerging as disease-modifying targets in MS. Surprisingly, as first demonstrated here, 4-AP inhibits neuronal degenerin/epithelial Na+ (Deg/ENaC) channels, including ASIC and BLINaC. This effect is specific for 4-AP compared with its heterocyclic base, pyridine, and the related derivative, 4-methylpyridine; and akin to the actions of 4-AP on the structurally unrelated Kv channels, dose- and voltage-dependent. 4-AP has differential actions on distinct ASICs, strongly inhibiting ASIC1a channels expressed in central neurons but being without effect on ASIC3, which is enriched in peripheral sensory neurons. The voltage dependence of the 4-AP block and the single binding site for this inhibitor are consistent with 4-AP binding in the pore of Deg/ENaC channels as it does Kv channels, suggesting a similar mechanism of inhibition in these two classes of channels. These findings argue that effects on both Kv and Deg/ENaC channels should be considered when evaluating the actions of 4-AP. Importantly, the current results are consistent with 4-AP influencing the symptoms of MS as well as the course of the disease because of inhibitory actions on Kv and ASIC channels, respectively.
Reciprocation and interchange of grooming, agonistic support, feeding tolerance, and aggression in semi‐free‐ranging Barbary macaques

Evidence from a range of primate species indicates that grooming can be exchanged either for itself or for other rank‐related “commodities,” such as agonistic support, feeding tolerance, or reduced aggression. Patterns of exchange behavior have been found to vary considerably between species, and understanding the causes of this variation is central to the study of the evolution of primate social systems. It is, therefore, essential that exchange behavior is examined in a wide range of species and settings. This article is the first to explore the reciprocation and interchange of grooming in the Barbary macaque (Macaca sylvanus). We collected focal data on semi‐free‐ranging adult female Barbary macaques at Trentham Monkey Forest, England, and analyzed dyadic data using Generalized Linear Mixed Models. We found evidence for the reciprocal exchange of grooming and for the interchange of grooming for agonistic support and tolerance while feeding. There was no evidence that grooming was traded for a reduction in aggression; indeed, we found a positive relationship between aggression given and grooming received. This may reflect the “extortion” of grooming from subordinates by dominant animals. These results will facilitate comparative analyses of exchange behavior by adding to the current database a new species, characterized by a different social style from those macaque species previously investigated. Am. J. Primatol. 73:1127–1133, 2011. © 2011 Wiley Periodicals, Inc.
Pressure ulcers: knowledge and attitude of nurses and nursing assistants in Belgian nursing homes.

AIMS To gain insight into the knowledge and attitudes of nurses and nursing assistants and to study the correlation between knowledge, attitudes and the compliance with the pressure ulcer prevention guidelines provided to residents at risk of pressure ulcers in nursing homes. BACKGROUND There is a lack of evidence on knowledge and attitudes of nurses and nursing assistants towards pressure ulcer prevention in nursing homes. DESIGN A cross-sectional multi-centre study. METHODS A convenience sample of nine Belgian nursing homes, representing 18 wards was chosen in the study. In total, 145 nurses and nursing assistants were included. The compliance with the guidelines was evaluated in 615 residents, and data were collected using validated instruments. RESULTS Fully compliant prevention was found in only 6·9% of the residents at risk. The mean knowledge score of the nurses was 29·3 vs. 28·7% for the nursing assistants. The overall attitude score was 74·5%, and attitude scores were significantly different between nurses and nursing assistants. Nurses showed to have a more positive attitude towards pressure ulcer prevention than nursing assistants, respectively 78·3 and 72·3%. A more positive attitude was a significant predictor of pressure ulcer prevention compliance with the guidelines provided to residents at risk of pressure ulcers in nursing homes. CONCLUSIONS Knowledge about pressure ulcer prevention of both nurses and nursing assistants in nursing homes was low. Attitudes were a significant predictor of the application of fully compliant prevention in residents at risk. RELEVANCE TO CLINICAL PRACTICE Pressure ulcer prevention is an important aspect in daily care for residents at risk in nursing homes. These insights will contribute to evidence-based practice in this area of care and will form the basis for the development of an education strategy for pressure ulcer prevention and management in nursing homes.
Acute and Per-Acute Gangrenous Mastitis in Goats and its Management

A total of six clinical cases of gangrenous mastitis in goats were studied. Acute and per-acute mastitic quarters were associated with either E.coli alone or mixed infection of Staph. aureus and E. coli. The organisms were sensitive to amoxicillin, cloxacilin, gentamicin and cholor-tetracycline but resistant to penicillin and streptomycin. The acute mastitic quarters were treated by intramammary infusion of inj. Gentamicin mixed with inj. dexamethasone and 1.5 ml water for injection per affected quarter twice daily for 4 days; in addition to these, supportive therapy including parentral administration of Inj. DNS (5%) and Inj. Melonex plusa for per-acute cases were also provided. Besides, one acute case was also treated with amoxicillin and cloxacilin (parentral and intramammarily). Per-acute gangrenous mastitic quarter which was refractory to the treatment required partial removal of it surgically.
Suffering and smiling: West African immigrant women's experience of intimate partner violence.

AIMS AND OBJECTIVES This study reports the intimate partner violence experiences of West African women living in Australia. BACKGROUND Increasing diversity in Australia's population presents new and complex challenges to nurses and other health care providers, particularly in relation to the health needs of immigrant women. DESIGN A qualitative naturalistic inquiry design was used. METHOD A convenience sample of 21 West African immigrant women in Australia who were 18 years and over were engaged in face-to-face, in-depth interviews and asked to talk about their health experiences. The interviews were transcribed verbatim and analysed thematically. Intimate partner violence was revealed as a major theme in this analysis. RESULTS Data revealed that eighteen of the women had experienced intimate partner violence. The women's accounts of intimate partner violence were dominated by two subthemes 'suffering in silence' and 'reluctance to seek help. ' CONCLUSION Findings revealed intimate partner violence as a significant issue for the newly migrated African women who participated in this study. RELEVANCE TO CLINICAL PRACTICE Intimate partner violence is associated with significant adverse physical and psychological health outcomes. It is important that nurses understand the cultural barriers that can impede immigrant women's ability to seek out and receive appropriate support and intervention and provide opportunities for women to disclose experiences of intimate partner violence.
Empathy building in undergraduate medical students through an interaction with Persons with Disabilities in their natural home environment A Descriptive Qualitative study

Background: Empathetic communication is regarded as the best approach to meet the needs of a person with disabilities (PWDs) and is critical to the development of professionalism in the undergraduate medical students. The purpose of the study is to enhance empathy in the undergraduate medical students by exposing them to PWDs in their natural home environment. Methods: Through home visiting technique a group of 15 medical students (3 batches of 5 each) were taken in the community for interaction with PWDs. 5 in-depth interviews & 3 focus group discussions were done in order to explore students’ emotions. Households with PWDs were identified with the help of local NGO “Disabled People Development Organization”. Twenty five households with PWDs were visited, 05 on daily basis. Students attended few sessions on communication skills & a motivating talk was given by the president of organization, who himself was physically disabled. Data regarding the total number of households with PWDs visited, stating the nature of their disability was recorded on the daily basis. Their disabilities were diverse and ranged in severity from mild mobility limitations to total dependence for care. Results: Students’ shared their emotions and experience of interaction with PWDs in a very positive manner and expressed how this interaction served to inculcate compassion and empathy among them. It was a real display of student’s emotions and feelings, truly reflective of their concern and empathy for the suffering community. Conclusion: Real life community exposure is critical to enhancement of empathy in the undergraduate medical students. Household community surveys should be incorporated into undergraduate medical curriculum which will help students to adopt the holistic health approach.
The identification of multiple symptom clusters and their effects on functional performance in cancer patients.

AIMS AND OBJECTIVES To identify cancer-related symptom clusters, to explore their inter-relationships and to examine the effects of single symptoms and the synergistic effects of symptom clusters on functional performance using path analysis by structural equation modelling in patients with various types of cancer. BACKGROUND Recent studies suggest that cancer patients frequently experience three or more concurrent related symptoms and that this clustering of symptoms is likely to have negative synergistic impacts on outcomes, because of the complicated dynamics of clusters. DESIGN A cross-sectional design. METHODS One hundred and ten patients with various types of cancer were recruited as in- and out-patients at a University Hospital in Incheon, South Korea. Data collection was performed using a questionnaire and by direct interview. Pain, insomnia, fatigue, depression and functional performance were measured. RESULTS The developed model was composed of antecedents, symptom clusters and outcomes. Of the symptoms often encountered as clusters in cancer patients, insomnia, depression and fatigue were found to have significant single (direct) effects on functional performance. Seven symptom clusters were identified between pain and functional performance, three between insomnia and functional performance and one between depression and functional performance. These single symptoms and symptom clusters were found to have significant synergistic effects on functional performance and to explain 24% of functional performance variance. CONCLUSIONS Multiple cancer-related symptom clusters may occur and the dynamics within symptom clusters is complicated. Our findings provide sound evidence regarding the importance of assessing and managing clusters of symptoms simultaneously rather than focusing on single symptoms. RELEVANCE TO CLINICAL PRACTICE A comprehensive understanding of symptom clusters in cancer patients would help establish valid diagnostic symptom cluster entities and aid the development of subjective/objective phenotypic criteria for symptom cluster based diagnoses and of nursing care protocols for managing symptom clusters.
Intrinsic Selectivity of Notch 1 for Delta-like 4 Over Delta-like 1*

Background: Notch signaling controls cell fate decisions in all metazoan organisms. Results: The Notch1 receptor exhibits a binding affinity for the ligand Delta-like 4 at least an order of magnitude stronger than for its close homologue, Delta-like 1. Conclusion: Intrinsic binding preferences exist for specific Notch receptor-ligand pairs. Significance: Binding selectivity among different potential receptor-ligand complexes may influence receptor-mediated responses of developmental signaling pathways. Notch signaling makes critical contributions to cell fate determination in all metazoan organisms, yet remarkably little is known about the binding affinity of the four mammalian Notch receptors for their three Delta-like and two Jagged family ligands. Here, we utilized signaling assays and biochemical studies of purified recombinant ligand and receptor molecules to investigate the differences in signaling behavior and intrinsic affinity between Notch1-Dll1 and Notch1-Dll4 complexes. Systematic deletion mutagenesis of the human Notch1 ectodomain revealed that epidermal growth factor (EGF) repeats 6–15 are sufficient to maintain signaling in a reporter assay at levels comparable with the full-length receptor, and identified important contributions from EGF repeats 8–10 in conveying an activating signal in response to either Dll1 or Dll4. Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. Plate-based and cell binding assays revealed a specific, calcium-dependent interaction between cell-surface and recombinant Notch receptors and ligand molecules. Finally, direct measurement of the binding affinity of Notch1 EGF repeats 6–15 for Dll1 and Dll4 revealed that Dll4 binds with at least an order of magnitude higher affinity than Dll1. Together, these studies give new insights into the features of ligand recognition by Notch1, and highlight how intrinsic differences in the biochemical behavior of receptor-ligand complexes can influence receptor-mediated responses of developmental signaling pathways.
Interleukin-4 Induces Up-regulation of Endothelial Cell Claudin-5 through Activation of FoxO1

Background: IL-4 protects vascular endothelial cells (ECs) from complement-mediated junctional injury and cytotoxicity. Results: IL-4 induces up-regulated expression of junctional claudin-5 through STAT6 and FoxO1. Claudin-5 up-regulation contributes to, but is not sufficient, for protection. Conclusion: IL-4-induced claudin-5 is an important component in protection of ECs from complement. Significance: Regulation of claudin-5 expression may play a role controlling EC inflammatory injury. Injury to endothelial cells (ECs) often results in cell retraction and gap formation. When caused by antigen aggregation or complement, this injury can be prevented by pretreatment of the ECs with IL-4, suggesting that IL-4 modifies the intercellular junction. Therefore, we investigated the effects of IL-4 on expression of intercellular junction proteins and whether such effects are required for IL-4-induced resistance of ECs against complement-mediated injury. We found that IL-4 induces up-regulation of the junction protein claudin-5 in porcine ECs through activation of Jak/STAT6 and phosphorylation and translocation of FoxO1 from the nucleus to the cytoplasm. Increased claudin-5 expression resulted in increased transmembrane electrical resistance of the endothelial monolayer and participated in IL-4-induced protection of the ECs from complement injury. Down-regulation of FoxO1 using siRNA by itself caused up-regulation of claudin-5 expression and partial protection from cytotoxicity. This protection was enhanced by stimulation with IL-4. We previously reported that increased phospholipid synthesis and mitochondrial protection were required for IL-4-induced resistance of ECs against complement injury and now we demonstrate a contribution of claudin-5 expression in IL-4-induced protection.
Joint Protection and Rehabilitation in Chronic Rheumatic Disorders

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Regulation of the Activity of Lactate Dehydrogenases from Four Lactic Acid Bacteria*

Background: Lactate dehydrogenases (LDHs) are key metabolic enzymes in lactic acid bacteria (LAB). Results: The effects of fructose 1,6-bisphosphate, phosphate, pH, and ionic strength on enzyme activity differ for six LDHs from four LAB. Conclusion: The regulation of LDH activity differs among LAB. Significance: These results have implications for understanding enzyme evolutionary adaptation, for quantitative comparative modeling, and for biotechnological application of LAB. Despite high similarity in sequence and catalytic properties, the l-lactate dehydrogenases (LDHs) in lactic acid bacteria (LAB) display differences in their regulation that may arise from their adaptation to different habitats. We combined experimental and computational approaches to investigate the effects of fructose 1,6-bisphosphate (FBP), phosphate (Pi), and ionic strength (NaCl concentration) on six LDHs from four LABs studied at pH 6 and pH 7. We found that 1) the extent of activation by FBP (Kact) differs. Lactobacillus plantarum LDH is not regulated by FBP, but the other LDHs are activated with increasing sensitivity in the following order: Enterococcus faecalis LDH2 ≤ Lactococcus lactis LDH2 < E. faecalis LDH1 < L. lactis LDH1 ≤ Streptococcus pyogenes LDH. This trend reflects the electrostatic properties in the allosteric binding site of the LDH enzymes. 2) For L. plantarum, S. pyogenes, and E. faecalis, the effects of Pi are distinguishable from the effect of changing ionic strength by adding NaCl. 3) Addition of Pi inhibits E. faecalis LDH2, whereas in the absence of FBP, Pi is an activator of S. pyogenes LDH, E. faecalis LDH1, and L. lactis LDH1 and LDH2 at pH 6. These effects can be interpreted by considering the computed binding affinities of Pi to the catalytic and allosteric binding sites of the enzymes modeled in protonation states corresponding to pH 6 and pH 7. Overall, the results show a subtle interplay among the effects of Pi, FBP, and pH that results in different regulatory effects on the LDHs of different LABs.
Tracking the route to sustainability: a service evaluation tool for an advance care planning model developed for community palliative care services.

AIMS AND OBJECTIVES The study aim was to develop a service evaluation tool for an advance care planning model implemented in community palliative care. BACKGROUND Internationally, advance care planning programmes usually measure success by completion rate of advance directives or plans. This outcome measure provides little information to assist nurse managers to embed advance care planning into usual care and measure their performance and quality over time. An evaluation tool was developed to address this need in Australian community palliative care services. DESIGN Multisite action research approach. METHODS Three community palliative care services located in Victoria, Australia, participated. Qualitative and quantitative data collection strategies were used to develop the Advance Care Planning-Service Evaluation Tool. RESULTS The Advance Care Planning-Service Evaluation Tool identified advance care planning progress over time across three stages of Establishment, Consolidation and Sustainability within previously established Model domains of governance, documentation, practice, education, quality improvement and community engagement. The tool was used by nurses either as a peer-assessment or self-assessment tool that assisted services to track their implementation progress as well as plan further change strategies. CONCLUSION The Advance Care Planning-Service Evaluation Tool was useful to nurse managers in community palliative care. It provided a clear outline of service progress, level of achievement and provided clear direction for planning future changes. RELEVANCE TO CLINICAL PRACTICE The Advance Care Planning-Service Evaluation Tool enables nurses in community palliative care to monitor, evaluate and plan quality improvement of their advance care planning model to improve end-of-life care. As the tool describes generic healthcare processes, there is potential transferability of the tool to other types of services.
Autescala de Zung para depresión como predictor de la respuesta sensorial y autonómica al dolor.

Evidencia clinica y experimental apoyan una relacion entre la susceptibilidad al dolor cronico y la depresion subyacente. Sin embargo, no esta claro si los instrumentos de evaluacion clinica para depresion que existen permiten vincular ambos trastornos. Asi, se evaluo la autoescala para depresion de Zung y sus diferentes categorias: afectiva, fisiologica, motora y psicologica como posible predictor de alteraciones sensoriales y autonomicas, asi como su vulnerabilidad a dolores clinicos cronicos. A 32 controles sanos y 11 sujetos con depresion menor sin tratamiento, se les indujo isquemia mediante un torniquete sobre el brazo dominante, y luego seguido de parestesias durante la reperfusion del brazo al ser liberado el torniquete. El dolor muscular isquemico, las parestesias post-isquemicas y la respuesta cardiovascular fueron monitoreadas durante el procedimiento. El puntaje de la categoria afectiva se correlaciono linealmente en forma individual con el mayor numero de variables y se ajusto a un modelo de regresion multiple que explicaba casi un 100% la varianza, con una contribucion de las variables sensoriales y autonomicas de un 70% y 30%, respectivamente. Ademas, la categoria afectiva fue un 50% mayor en los sujetos con dolor clinico persistente. El indice total de Zung y las otras categorias tuvieron un menor numero de correlaciones lineales individuales y modelos de correlacion multiple que solo explicaban entre 30-70% de la varianza, con una contribucion mas predominante de las variables autonomicas (20-50%), especialmente en la categoria psicologica. Esto sugiere que la categoria afectiva puede predecir alteraciones sensoriales cutaneo-musculares con mayor eficacia que el indice total de Zung.