Miracle-dz/UniFAR-FTUs huggingface dataset:
Myosin Regulatory Light Chain (RLC) Phosphorylation Change as a Modulator of Cardiac Muscle Contraction in Disease

Background: Cardiac myosin regulatory light chain (RLC) phosphorylation alters cardiac muscle function. Results: Phosphorylation affects mechanical parameters of cardiac muscle contraction during shortening. Conclusion: Phosphorylation impacts mechanical function of cardiac muscle and is altered during cardiac disease. Significance: Understanding RLC regulation by phosphorylation in cardiac muscle contraction is crucial for understanding changes in disease. Understanding how cardiac myosin regulatory light chain (RLC) phosphorylation alters cardiac muscle mechanics is important because it is often altered in cardiac disease. The effect this protein phosphorylation has on muscle mechanics during a physiological range of shortening velocities, during which the heart generates power and performs work, has not been addressed. We have expressed and phosphorylated recombinant Rattus norvegicus left ventricular RLC. In vitro we have phosphorylated these recombinant species with cardiac myosin light chain kinase and zipper-interacting protein kinase. We compare rat permeabilized cardiac trabeculae, which have undergone exchange with differently phosphorylated RLC species. We were able to enrich trabecular RLC phosphorylation by 40% compared with controls and, in a separate series, lower RLC phosphorylation to 60% of control values. Compared with the trabeculae with a low level of RLC phosphorylation, RLC phosphorylation enrichment increased isometric force by more than 3-fold and peak power output by more than 7-fold and approximately doubled both maximum shortening speed and the shortening velocity that generated peak power. We augmented these measurements by observing increased RLC phosphorylation of human and rat HF samples from endocardial left ventricular homogenate. These results demonstrate the importance of increased RLC phosphorylation in the up-regulation of myocardial performance and suggest that reduced RLC phosphorylation is a key aspect of impaired contractile function in the diseased myocardium.
Understanding acute care nurse practitioner communication and decision-making in healthcare teams.

AIMS AND OBJECTIVES This paper aims to describe communication and decision-making in healthcare teams following the introduction of an acute care nurse practitioner role. BACKGROUND Healthcare teams need to establish clear processes for communication and decision-making about patient care to be effective. Little is known about how acute care nurse practitioners affect these team processes. DESIGN Observational/descriptive study. METHODS Structured non-participant observations of acute care nurse practitioners and healthcare team members during routine patient care activities were completed to identify the verbal and non-verbal behaviours. Data were collected in two hospitals in one Canadian province from March-May 2009 for a total of 17 hours and 23 minutes. Descriptive statistics were generated. RESULTS Differences in communication and decision-making were noted between the cases. The acute care nurse practitioners in Case 1 spoke most frequently with physicians when making patient care decisions while the acute care nurse practitioners in Case 2 spoke most frequently with the nurses. The acute care nurse practitioners needed to validate all patient care decisions if prescriptive authority had not been transferred to them. DISCUSSION Much of the potential of acute care nurse practitioner roles rests on the ability to enact the full scope of their role. Acute care nurse practitioner scope of practice depends on the legislation, the transfer of decision-making authority in the organisation, and the messages received form the medical and nursing leadership group. CONCLUSIONS This appears to be the first in-depth description of communication and decision-making in healthcare teams following the introduction of acute care nurse practitioners and furthers our understanding of how system-level imperatives filter down to healthcare teams. RELEVANCE TO CLINICAL PRACTICE The transfer of prescriptive authority to acute care nurse practitioners affected communication and decision-making and changed the way routine activities were conducted.
Visual functioning in nursing home residents: information in client records.

AIM AND OBJECTIVES To improve (eye)care in nursing homes by reporting and assessing visual functioning to enhance professional caregivers' awareness of visual problems. BACKGROUND Older adults experience visual problems owing to biological ageing or eye disease. In the Netherlands, the prevalence of visual impairments is the highest in the subgroup of nursing home residents (41.3%). These impairments influence quality of life in terms of limiting daily activities and participation in social activities. Furthermore, 63% of visual problems are defined as 'avoidable blindness'. For this reason, screening of visual functioning in the nursing home is of major importance. Moreover, visual functioning should also be taken into account to prevent the incidence of falls. DESIGN A field study on recorded information of visual functioning and visual assessment in nursing homes. METHODS Assessment of visual functioning of 259 residents in nursing homes. Subsequently, recorded information in client files is related to the assessment outcome. RESULTS Only in 101 (39%) of the 259 client records was some information on visual functioning found in client files. Whether a prescription for new glasses was dispensed made no difference in reporting on visual functioning in the client record. In more than half of the cases assessed as 'low vision or blindness', no information about visual functioning was found. Furthermore, no information was found in 31% (80/259) cases of suspected visual problems (referrals). A significant proportion of client records (p < 0.05) showed no recorded information in cases of referral for further check-up. CONCLUSIONS In this study, one-third of nursing homes residents have visual problems, needing examination by an ophthalmologist. Problems with visual functioning should be assessed and captured in client records. Awareness of residents' visual functioning is a prerequisite for adapting basic daily care to the residents' needs.
The genetic population structure of wild western lowland gorillas (Gorilla gorilla gorilla) living in continuous rain forest

To understand the evolutionary histories and conservation potential of wild animal species it is useful to assess whether taxa are genetically structured into different populations and identify the underlying factors responsible for any clustering. Landscape features such as rivers may influence genetic population structure, and analysis of structure by sex can further reveal effects of sex‐specific dispersal. Using microsatellite genotypes obtained from noninvasively collected fecal samples we investigated the population structure of 261 western lowland gorillas (WLGs) (Gorilla gorilla gorilla) from seven locations spanning an approximately 37,000 km2 region of mainly continuous rain forest within Central African Republic (CAR), Republic of Congo and Cameroon. We found our sample to consist of two or three significantly differentiated clusters. The boundaries of the clusters coincided with courses of major rivers. Moreover, geographic distance detoured around rivers better‐explained variation in genetic distance than straight line distance. Together these results suggest that major rivers in our study area play an important role in directing WLG gene flow. The number of clusters did not change when males and females were analyzed separately, indicating a lack of greater philopatry in WLG females than males at this scale. Am. J. Primatol. 76:868–878, 2014. © 2014 Wiley Periodicals, Inc.
Comparison of nurse practitioners' perceptions of required competencies and self-evaluated competencies in Taiwan.

AIMS AND OBJECTIVES This paper is a report of a study conducted to investigate differences between nurse practitioners' perceptions of the importance of required competencies and their self-evaluated existing competencies, and the main factors influencing these differences. BACKGROUND The difference between nurse practitioners' perceptions of required competencies and their existing competencies has never been investigated. Therefore, it is still uncertain whether these two competencies differ. DESIGN A nationwide survey study was authorised by the Department of Health (DOH) in Taiwan. METHODS For this nationwide survey study, the Questionnaire of Competencies in the Nurse Practitioner's Role was mailed to all nurse practitioners who qualified for the first annual national NP licence exam in Taiwan. Of 582 questionnaires distributed, 374 valid questionnaires were returned for a response rate of 64.2%. RESULTS The scores for required competencies were all higher than existing competencies. The competencies with largest differences were (in increasing order) clinical research, direct care, and leadership and reform. The competencies with smallest differences were (in ascending order) medical assistance, communication and coordination, and ethical decision-making. Differences in the total score between required and existing competencies were significantly influenced by nurse practitioners' age, seniority as nurse practitioner, whether the nurse practitioners' institution had a nurse practitioner advancement system, and the number of patients under their care. CONCLUSIONS Nurse practitioners' perceptions of the importance of their expected role competencies were significantly greater in most cases than their actual competencies. RELEVANCE TO CLINICAL PRACTICE These findings could serve as a reference to improve cultivation of the NP system in Taiwan, to strengthen professional competencies in NP training programs.
Inhibition of Amyloid Precursor Protein Processing Enhances Gemcitabine-mediated Cytotoxicity in Pancreatic Cancer Cells*

Background: Amyloid precursor protein (APP) and ADAM10, main α-secretase involved in generation of secreted APP (sAPPα), are overexpressed in pancreatic cancer. Results: Inhibition of APP processing by ADAM10 prevents anchorage independent growth and survival of cancer cells. Conclusion: Inhibition of sAPPα generation enhances chemotherapeutic potential of gemcitabine. Significance: Supplementing established pancreatic cancer therapy regimen with sAPPα inhibition will significantly improve the efficacy of treatment. Pancreatic adenocarcinoma or pancreatic cancer is often diagnosed at a very late stage at which point treatment options are minimal. Current chemotherapeutic interventions prolong survival marginally, thereby emphasizing the acute need for better treatment options to effectively manage this disease. Studies from different laboratories have shown that the Alzheimer disease-associated amyloid precursor protein (APP) is overexpressed in various cancers but its significance is not known. Here we sought to determine the role of APP in pancreatic cancer cell survival and proliferation. Our results show that pancreatic cancer cells secrete high levels of sAPPα, the α-secretase cleaved ectodomain fragment of APP, as compared with normal non-cancerous cells. Treatment of cells with batimastat or GI254023X, inhibitors of the α-secretase ADAM10, prevented sAPPα generation and reduced cell survival. Additionally, inhibition of sAPPα significantly reduced anchorage independent growth of the cancer cells. The effect of batimastat on cell survival and colony formation was enhanced when sAPPα downregulation was combined with gemcitabine treatment. Moreover, treatment of batimastat-treated cells with recombinant sAPPα reversed the inhibitory effect of the drug thereby indicating that sAPPα can indeed induce proliferation of cancer cells. Down-regulation of APP and ADAM10 brought about similar results, as did batimastat treatment, thereby confirming that APP processing is important for growth and proliferation of these cells. These results suggest that inhibition of sAPPα generation might enhance the effectiveness of the existing chemotherapeutic regimen for a better outcome.
Single-molecule Investigation of Substrate Binding Kinetics and Protein Conformational Dynamics of a B-family Replicative DNA Polymerase*

Background: DNA polymerases use a multistep mechanism to faithfully replicate DNA. Results: Replicative DNA polymerase PolB1 binds DNA in multiple conformations that are affected by nucleotide or mismatched DNA binding. Conclusion: Modulation of conformational dynamics and DNA binding kinetics affects the replication fidelity of PolB1. Significance: Single-molecule techniques can reveal subtle differences in substrate binding properties and conformational dynamics of a DNA polymerase. Replicative DNA polymerases use a complex, multistep mechanism for efficient and accurate DNA replication as uncovered by intense kinetic and structural studies. Recently, single-molecule fluorescence spectroscopy has provided new insights into real time conformational dynamics utilized by DNA polymerases during substrate binding and nucleotide incorporation. We have used single-molecule Förster resonance energy transfer techniques to investigate the kinetics and conformational dynamics of Sulfolobus solfataricus DNA polymerase B1 (PolB1) during DNA and nucleotide binding. Our experiments demonstrate that this replicative polymerase can bind to DNA in at least three conformations, corresponding to an open and closed conformation of the finger domain as well as a conformation with the DNA substrate bound to the exonuclease active site of PolB1. Additionally, our results show that PolB1 can transition between these conformations without dissociating from a primer-template DNA substrate. Furthermore, we show that the closed conformation is promoted by a matched incoming dNTP but not by a mismatched dNTP and that mismatches at the primer-template terminus lead to an increase in the binding of the DNA to the exonuclease site. Our analysis has also revealed new details of the biphasic dissociation kinetics of the polymerase-DNA binary complex. Notably, comparison of the results obtained in this study with PolB1 with those from similar single-molecule studies with an A-family DNA polymerase suggests mechanistic differences between these polymerases. In summary, our findings provide novel mechanistic insights into protein conformational dynamics and substrate binding kinetics of a high fidelity B-family DNA polymerase.
An economic analysis of repositioning for the prevention of pressure ulcers.

AIMS AND OBJECTIVES To compare pressure ulcer incidence and costs associated with repositioning older individuals in long-term care using two different repositioning regimes. BACKGROUND Repositioning has not always been integrated into pressure ulcer preventative methods, with arguments that it is an expensive procedure in terms of personnel and time. DESIGN Participants were randomly allocated to the experimental group (n = 99; repositioned every 3 hours, using the 30° tilt) and the control group (n = 114 standard care, repositioned every 6 hours, using the 90° lateral rotation). The analysis explored the incidence of pressure ulcer development and the cost difference between the two repositioning schedules, over a 4-week period. RESULTS The mean daily nurse time for repositioning was 18·5 minutes (experimental) and 24·5 minutes (control). Nurse time cost per patient over the study period was €206·6 (experimental) and €253·1 (control), 96·6% of participants (experimental) remained free of pressure ulcers, compared with 88·1% (control). The cost per patient free of ulcer was €213·9 (experimental) and €287·3 (control). Projected annual costs were estimated for the 588 (53·5%) residents in the 12 study sites requiring repositioning. The cost would be €1·59 m (experimental) and €2·10 m (control), a cost difference of €510,000. This represents a difference of 58·8 hours of nurse time, equivalent to approximately 12 full time nurses across the 12 sites. CONCLUSION Repositioning every 3 hours, using 30° tilt, has been shown to be more effective in less costly in terms of nurse time compared with standard care. RELEVANCE TO CLINICAL PRACTICE Repositioning individuals at risk of pressure ulcer development makes both economic and clinical sense, thereby supporting the EPUAP/NPUAP 2009 guidelines.
“Snapshots” of Ispinesib-induced Conformational Changes in the Mitotic Kinesin Eg5*

Background: Ispinesib is a small molecule inhibitor of Eg5 and induces neck linker docking. Results: Ispinesib binding to Eg5 induces subsequent movement of switch II. Conclusion: Conformational changes in L5 can alter the orientation of the neck linker regardless of the state of the catalytic site. Significance: L5 is a key regulator of both the catalytic site and switch II. Kinesins comprise a superfamily of molecular motors that drive a wide variety of cellular physiologies, from cytoplasmic transport to formation of the bipolar spindle in mitosis. These differing roles are reflected in corresponding polymorphisms in key kinesin structural elements. One of these is a unique loop and stem motif found in all kinesins and referred to as loop 5 (L5). This loop is longest in the mitotic kinesin Eg5 and is the target for a number of small molecule inhibitors, including ispinesib, which is being used in clinical trials in patients with cancer. In this study, we have used x-ray crystallography to identify a new structure of an Eg5-ispinesib complex and have combined this with transient state kinetics to identify a plausible sequence of conformational changes that occur in response to ispinesib binding. Our results demonstrate that ispinesib-induced structural changes in L5 from Eg5 lead to subsequent changes in the conformation of the switch II loop and helix and in the neck linker. We conclude that L5 in Eg5 simultaneously regulates the structure of both the ATP binding site and the motor's mechanical elements that generate force.
Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D.

Reactive nitrogen species (RNS) generated after exposure to radiation have been implicated in lung injury. Surfactant protein D (SP-D) is a pulmonary collectin that suppresses inducible nitric oxide synthase (iNOS)-mediated RNS production. Herein, we analyzed the role of iNOS and SP-D in radiation-induced lung injury. Exposure of wild-type (WT) mice to γ-radiation (8 Gy) caused acute lung injury and inflammation, as measured by increases in bronchoalveolar lavage (BAL) protein and cell content at 24 h. Radiation also caused alterations in SP-D structure at 24 h and 4 weeks post exposure. These responses were blunted in iNOS(-/-) mice. Conversely, loss of iNOS had no effect on radiation-induced expression of phospho-H2A.X or tumor necrosis factor (TNF)-α. Additionally, at 24 h post radiation, cyclooxygenase expression and BAL lipocalin-2 levels were increased in iNOS(-/-) mice, and heme oxygenase (HO)-1(+) and Ym1(+) macrophages were evident. Loss of SP-D resulted in increased numbers of enlarged HO-1(+) macrophages in the lung following radiation, along with upregulation of TNF-α, CCL2, and CXCL2, whereas expression of phospho-H2A.X was diminished. To determine if RNS play a role in the altered sensitivity of SP-D(-/-) mice to radiation, iNOS(-/-)/SP-D(-/-) mice were used. Radiation-induced injury, oxidative stress, and tissue repair were generally similar in iNOS(-/-)/SP-D(-/-) and SP-D(-/-) mice. In contrast, TNF-α, CCL2, and CXCL2 expression was attenuated. These data indicate that although iNOS is involved in radiation-induced injury and altered SP-D structure, in the absence of SP-D, it functions to promote proinflammatory signaling. Thus, multiple inflammatory pathways contribute to the pathogenic response to radiation.
Persistence with hepatitis C therapy in the Department of Veterans Affairs

Background: Persistence with Hepatitis C therapy has been identified as a key variable for predicting treatment success. The primary purpose of this study was to assess the persistence with therapy for patients undergoing hepatitis C treatment in the VA healthcare system with two forms of combination therapies: peginterferon alfa‐2a with Ribavirin (peg‐IFN alpha‐2a/Rib) and peginterferon alpha‐2b with Ribavirin (peg‐IFN alpha‐2b/Rib).
Effect of the ostreolysin A/pleurotolysin B pore-forming complex on neuroblastoma cell morphology and intracellular Ca²⁺ activity.

Ostreolysin A (OlyA) and pleurotolysin B (PlyB), isolated from edible oyster mushrooms, form a cytolytic complex (OlyA/PlyB) in membrane cells that causes respiratory arrest. This study evaluated the mechanisms underlying cytotoxic OlyA/PlyB activity in neuroblastoma NG108-15 cells. Confocal microscopy with morphometric analysis revealed that OlyA/PlyB increased the 3-dimensional projected area of differentiated cells. Iso-osmotic replacement of NaCl by sucrose or Na-isethionate prevented the cellular swelling. This suggests that formation of cellular edema requires the presence of Na(+) and/or Cl(-) in the extracellular space and may be related to an influx of Na(+) and/or a shift in Cl(-), which induce a marked influx of water that is ultimately responsible for cellular swelling. In addition, extracellular Ca(2+) moderately contributed to the swelling because benzamil (10 µM), a 3Na(+)/Ca(2+) exchange (NCX) inhibitor, and Ca(2+)-free medium partially prevented this response. Fluorometric measurements revealed that OlyA/PlyB, at approximately 15-fold higher concentrations, increased the intracellular Ca(2+) activity [Ca(2+)]i. This increase was dependent on the presence of Na(+) and Ca(2+) in the external medium and was sensitive to benzamil. It is thus likely that a switch in the NCX mode, associated with the de novo formation of non-selective ion pores by OlyA/PlyB in cellular plasma membranes, plays an important role in this effect. Overall, OlyA/PlyB affects neuroblastoma cell morphology and Ca(2+) homeostasis to influence the toxin-induced respiratory arrest.
To Evaluate the Role of Gabapentin as Preemptive Analgesic in Patients Undergoing Total Abdominal Hysterectomy in Epidural Anaesthesia

Gabapentin, a structural analogue of gamma-amino butyric acid, has been used as an anticonvulsant and antinociceptive drug but its mode of action is not well understood. Gabapentin has been demonstrated in various clinical studies to be of value as preemptive analgesic, and has shown to reduce the postoperative requirement of opioids. This study was conducted to evaluate the role of gabapentin as preemptive analgesic in patients undergoing total abdominal hysterectomy. Fifty patients with ASA grade I and II were assigned to receive 300mg gabapentin or placebo 2hr before surgery. Surgeries were conducted under combined spinal epidural anaesthesia. Post operatively, pain was assessed by visual analogue score (VAS) at 2, 4,8,12 and 24hrs. Patients were given epidural boluses of bupivacaine (0.125%) on demand. Total numbers of epidural boluses during first 24 hrs postoperatively were noted. Patients in gabapentin group have significantly lower VAS score 2, 4,8,12 and 24hrs postoperatively as compared to the placebo (1.3 ± 1.3, 2.3±1.4, 3.2 ± 2.1, 1.8 ± 1.7, 1.2 ± 1.3 vs. 2.1 ± 1.7, 3.2±1.6, 4.4 ± 1.2, 3.3 ± 1.1, 2.1 ± 1.2 respectively; P <0.05). Total numbers of epidural boluses were significantly less in gabapentin group (3.4±1.6 vs. 5.6±2.1, P<0.05). We conclude that preemptive use of gabapentin 300mg orally significantly reduces the number of postoperative epidural bolus requirement and postoperative pain in patients undergoing total abdominal hysterectomy under combined spinal epidural anaesthesia.