Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix

Summary Endothelial progenitor cells (EPCs) mobilize from the bone marrow in response to tissue injury and participate in vascular repair. However, there is limited data about the homing mechanisms of EPCs to vascular injury sites. Recently animal experiments indicated that platelets playa role in recruitment of EPCs to injury sites. However, data on the possible interaction between platelets and EPCs within the human system are limited. We, therefore, examined in-vitro human platelet-EPC interaction under static and flow conditions. Human EPCs were isolated from donated buffy coats by magnetic microbeads and flow cytometry cell sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed heterotypic aggregates with resting platelets under static conditions, an interaction that was greatly enhanced when platelets were activated by collagen, ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated platelets under shear stress of 2.5 dyn/cm2, EPCs tethered to platelayers and either adhered immediately or rolled a short distance before adhering. In addition, platelets promoted the colonization of adherent EPCs in culture conditions. Consistent with recent animal studies, these findings demonstrate that human EPCs interact in vitro with activated platelets under static and flow conditions, mediated through P-selectin–PSGL-1 interaction. This interaction may be a central mechanism for homing of EPCs to vascular injury sites.
Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord

Subunits of glutamate receptors participate in the regulation of sensory transmission at primary afferent synapses in the superficial laminae of dorsal horn (DH). We report here on the distribution of kainate receptors (GluR5/6/7) in these laminae by using light microscope (LM) and electron microscope (EM) immunocytochemistry. Standard (4%) paraformaldehyde fixation resulted in immunostaining for GluR5/6/7 in perikarya and fine processes in lamina II, especially its inner part (IIi). Preembedding EM revealed immunostaining of dendrites, perikarya, and occasional terminals, presumed to be from primary afferent fibers, at the center of glomerular arrangements. In rats perfused with 0.5% paraformaldehyde, LM showed a more punctate staining, mainly in the ventral part of lamina IIi and lamina III, than in material fixed with 4% paraformaldehyde. Approximately two‐thirds of GluR5/6/7 puncta were also immunostained with synaptophysin, suggesting that in material fixed with 0.5% paraformaldehyde, a large fraction of these are synaptic terminals. Double immunostained puncta disappear 4 days after dorsal rhizotomy, suggesting that most of GluR5/6/7‐immunopositive terminals are from primary afferent fibers. EM material fixed with 0.5% paraformaldehyde confirmed the expression of GluR5/6/7 in numerous synaptic endings with morphology of primary afferents. To determine the type of primary afferent terminals that express GluR5/6/7, two neuroanatomic tracers were injected in the sciatic nerves. The lectin from Bandeiraea simplicifolia (IB4) is selectively taken up by unmyelinated primary afferent fibers that terminate in the outer part of lamina II (IIo) and dorsal part of lamina IIi, whereas the B subunit of the cholera toxin (CTB) is selectively taken up by a broader class of primary afferents which, in superficial DH, terminate mainly in laminae I, ventral part of IIi, and III. Approximately 20% of GluR5/6/7‐immunoreactive puncta colocalized with IB4, whereas approximately 40% of GluR5/6/7‐immunoreactive puncta colocalized with CTB. The present study shows that (1) GluR5/6/7 does not have a clear and consistent spatial relation with postsynaptic sites, (2) a large number of primary afferents express GluR5/6/7, and (3) these are not limited to one functional class. Thus, modulation by glutamate of primary afferent terminals by means of kainate receptors in the superficial laminae of DH may predominantly involve presynaptic mechanisms. J. Comp. Neurol. 436:275–289, 2001. © 2001 Wiley‐Liss, Inc.
Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease

An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease.
Proximal Junctional Kyphosis in Adult Spinal Deformity Following Long Instrumented Posterior Spinal Fusion: Incidence, Outcomes, and Risk Factor Analysis

Study Design. To analyze patient outcomes and risk factors associated with proximal junctional kyphosis (PJK) in adults undergoing long posterior spinal fusion. Objectives. To determine the incidence of PJK and its effect on patient outcomes and to identify any risk factors associated with developing PJK. Summary of Background Data. The incidence of PJK and its affect on outcomes in adult deformity patients is unknown. No study has concentrated on outcomes of patients with PJK. Risk factors for developing PJK are unknown. Methods. Radiographic data on 81 consecutive adult deformity patients with minimum 2-year follow-up (average 5.3 years, range 2–16 years) treated with long instrumented segmental posterior spinal fusion was collected. Preoperative diagnosis was adult scoliosis, sagittal imbalance or both. Radiographic measurements analyzed included the sagittal Cobb angle at the proximal junction on preoperative, early postoperative, and final follow-up standing long cassette radiographs. Additional measurements used for analysis included the C7-Sacrum sagittal plumb and the T5–T12 sagittal Cobb. Postoperative SRS-24 scores were available on 73 patients. Results. Incidence of PJK as defined was 26%. Patients with PJK did not have lower outcomes scores. PJK did not produce a more positive sagittal C7 plumb. PJK was more common at T3 in the upper thoracic spine. Conclusions. Incidence of proximal junctional kyphosis was high, but SRS-24 scores were not significantly affected in patients with PJK. The sagittal C7 plumb was not significantly more positive in PJK patients. No patient, radiographic, or instrumentation variables were identified as risk factors for developing PJK.
Urinary proteomic analysis of chronic allograft nephropathy

The pathogenesis of progressive renal allograft injury, which is termed chronic allograft nephropathy (CAN), remains obscure and is currently defined by histology. Prospective protocol‐biopsy trials have demonstrated that clinical and standard laboratory tests are insufficiently sensitive indicators of the development and progression of CAN. The study aim was to determine if CAN could be characterized by urinary proteomic data and identify the proteins associated with disease. The urinary proteome of 75 renal transplant recipients and 20 healthy volunteers was analyzed using surface enhanced laser desorption and ionization MS. Patients could be classified into subgroups with normal histology and Banff CAN grades 2‐3 with a sensitivity of 86% and a specificity of 92% by applying the classification algorithm Adaboost to urinary proteomic data. Several urinary proteins associated with advanced CAN were identified including α1‐microglobulin, β2‐microglobulin, prealbumin, and endorepellin, the antiangiogenic C‐terminal fragment of perlecan. Increased urinary endorepellin was confirmed by ELISA and increased tissue expression of the endorepellin/perlecan ratio by immunofluoresence analysis of renal biopsies. In conclusion, analysis of urinary proteomic data has further characterized the more severe CAN grades and identified urinary endorepellin, as a potential biomarker of advanced CAN.
Using informative verbal exchanges to promote verb retrieval in nonfluent aphasia.

PURPOSE The goal of this study was to determine whether positive treatment effects of a modified constraint-induced language therapy focused on verb production would generalize to unpracticed items and tasks. METHOD Four individuals participated in a single-subject treatment design protocol. The treatment involved intensive practice producing verbs in sentences in an informative communicative exchange. Direct treatment outcome was examined by measuring the accuracy of producing practiced verbs in an action description task, a task similar to those used in treatment. Generalization was assessed by measuring production of unpracticed verbs and sentence grammaticality in the action description task and by measuring verb production and sentence grammaticality in 2 relatively unstructured (unpracticed) language tasks. RESULTS Two of the 4 participants showed a direct treatment effect, producing a greater number of practiced verbs in the action description task following treatment compared with before treatment. All participants improved sentence grammaticality following treatment, although grammaticality was not explicitly targeted in therapy. Generalization to unpracticed, less-structured tasks was variable across the participants. CONCLUSION Patterns of generalization may depend on participants' specific language deficits and production characteristics, on the language tasks used, and on the measures used to detect change and assess generalization.
Anticholinesterase and Antioxidant Activities of Fucoxanthin Purified from the Microalga Phaeodactylum Tricornutum

Hot extraction with acetone was the most efficient method for the extraction of fucoxanthin from Phaeodactylum tricornutum. The purified compound resulted in three main peaks consisted of the trans form along with two isomers. The structure of microalgal fucoxanthin was similar to that of brown seaweed, but the ratio of trans- to cis-form was different. The ratio of the cis-form increased as the extraction temperature increased. Fucoxanthin was unstable at high temperature, in acidic condition, and after long period of storage. Fucoxanthin exhibited strong activity against BChE, with an IC50 value of 1.97 mM and mixed inhibition type, whereas it had weak activity against AChE. The IC50 value on reducing power was 0.01 mM, which was much stronger than those of the positive controls. When the amount of cis-isomer increased by 2%, the scavenging activity against DPPH, hydrogen peroxide, superoxide anion, and reducing power decreased by 21.0, 10.3, 16.0, and 19.7%, respectively. Therefore, fucoxanthin could be a useful approach for Alzheimer's disease treatment.
American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

Objectives: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. ” Design: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006–2014). The PubMed/Medline/Embase literature (2006–14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. Measurements and Main Results: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. Conclusions: The major new recommendation in the 2014 update is consideration of institution—specific use of 1) a “recognition bundle” containing a trigger tool for rapid identification of patients with septic shock, 2) a “resuscitation and stabilization bundle” to help adherence to best practice principles, and 3) a “performance bundle” to identify and overcome perceived barriers to the pursuit of best practice principles.
Rocuronium exacerbates mechanical ventilation–induced diaphragm dysfunction in rats

Objective:Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin– proteasome pathway. Design:Randomized, controlled experiment. Setting:Basic animal science laboratory. Subjects:Male Wistar rats, 14 wks old. Interventions:Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium. Measurements and Main Results:In vitro diaphragm force was decreased more significantly after 24 hrs of mechanical ventilation combined with rocuronium infusion than after mechanical ventilation alone (e.g., tetanic force, −27%; p < .001 vs. mechanical ventilation). Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (−38% and −29%, respectively; p < .001 vs. control). Diaphragm hydroperoxide levels increased similarly in both mechanically ventilated groups. Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin–proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control). Significant correlations were found between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber dimensions. Conclusions:Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin–proteasome pathway. These findings could be important with regard to weaning failure in patients receiving this drug for prolonged periods in the intensive care unit setting.
Mitogen-Activated Protein Kinases with Distinct Requirements for Ste5 Scaffolding Influence Signaling Specificity in Saccharomyces cerevisiae

ABSTRACT Scaffold proteins are believed to enhance specificity in cell signaling when different pathways share common components. The prototype scaffold Ste5 binds to multiple components of the Saccharomyces cerevisiae mating pheromone response pathway, thereby conducting the mating signal to the Fus3 mitogen-activated protein kinase (MAPK). Some of the kinases that Ste5 binds to, however, are also shared with other pathways. Thus, it has been presumed that Ste5 prevents its bound kinases from transgressing into other pathways and protects them from intrusions from those pathways. Here we found that Fus3MAPK required Ste5 scaffolding to receive legitimate signals from the mating pathway as well as misdirected signals leaking from other pathways. Furthermore, increasing the cellular concentration of active Ste5 enhanced the channeling of inappropriate stimuli to Fus3. This aberrant signal crossover resulted in the erroneous induction of cell cycle arrest and mating. In contrast to Fus3, the Kss1 MAPK did not require Ste5 scaffolding to receive either authentic or leaking signals. Furthermore, the Ste11 kinase, once activated via Ste5, was able to signal to Kss1 independently of Ste5 scaffolding. These results argue that Ste5 does not act as a barrier that actively prevents signal crossover to Fus3 and that Ste5 may not effectively sequester its activated kinases away from other pathways. Rather, we suggest that specificity in this network is promoted by the selective activation of Ste5 and the distinct requirements of the MAPKs for Ste5 scaffolding.
PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium outer membrane

Significance The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) and glycerophospholipids (GPLs). Environmental regulation of LPS promotes bacterial resistance to host cationic antimicrobial peptides by altering surface charge and hydrophobicity. This work demonstrates that pathogenic Salmonella coordinately regulate GPL and LPS through the PhoPQ regulatory proteins and the OM palmitoyltransferase enzyme PagP. The broad conservation of PhoPQ and PagP in bacteria suggests that environmental regulation of OM GPL may be a conserved stress-response strategy for antimicrobial resistance. Improved understanding of OM GPL synthesis, transport, and modification could lead to new therapies that target the bacterial OM barrier. Gram-negative bacteria have two lipid membranes separated by a periplasmic space containing peptidoglycan. The surface bilayer, or outer membrane (OM), provides a barrier to toxic molecules, including host cationic antimicrobial peptides (CAMPs). The OM comprises an outer leaflet of lipid A, the bioactive component of lipopolysaccharide (LPS), and an inner leaflet of glycerophospholipids (GPLs). The structure of lipid A is environmentally regulated in a manner that can promote bacterial infection by increasing bacterial resistance to CAMP and reducing LPS recognition by the innate immune system. The gastrointestinal pathogen, Salmonella Typhimurium, responds to acidic pH and CAMP through the PhoPQ two-component regulatory system, which stimulates lipid A remodeling, CAMP resistance, and intracellular survival within acidified phagosomes. Work here demonstrates that, in addition to regulating lipid A structure, the S. Typhimurium PhoPQ virulence regulators also regulate acidic GPL by increasing the levels of cardiolipins and palmitoylated acylphosphatidylglycerols within the OM. Triacylated palmitoyl-PG species were diminished in strains deleted for the PhoPQ-regulated OM lipid A palmitoyltransferase enzyme, PagP. Purified PagP transferred palmitate to PG consistent with PagP acylation of both lipid A and PG within the OM. Therefore, PhoPQ coordinately regulates OM acidic GPL with lipid A structure, suggesting that GPLs cooperate with lipid A to form an OM barrier critical for CAMP resistance and intracellular survival of S. Typhimurium.
Generalized Joint Hypermobility and Risk of Lower Limb Joint Injury During Sport

Background: Generalized joint hypermobility is a highly prevalent condition commonly associated with joint injuries. The current literature has conflicting reports of the risk of joint injury in hypermobile sporting participants compared with their nonhypermobile peers. Systematic reviews have not been conclusive and no meta-analysis has been performed. Purpose: This review was undertaken to determine whether individuals with generalized joint hypermobility have an increased risk of lower limb joint injury when undertaking sporting activities. Study Design: Systematic review with meta-analysis. Methods: Studies were identified through a search without language restrictions of PubMed, CINAHL, Embase, and SportDiscus databases from the earliest date through February 2009 with subsequent handsearching of reference lists. Inclusion criteria for studies were determined before searching and all included studies underwent methodological quality assessment by 2 independent reviewers. Meta-analyses for joint injury of the lower limb, knee, and ankle were performed using a random effects model. The difference in injury proportions between hypermobility categories was tested with the z statistic. Results: Of 4841 identified studies, 18 met all inclusion criteria with methodological quality ranging from 1 of 6 to 5 of 6. A variety of tests of hypermobility and varied cutoff points to define the presence of generalized joint hypermobility were used, so the authors determined a standardized cutoff to indicate generalized joint hypermobility. Using this criterion, a significantly increased risk of knee joint injury for hypermobile and extremely hypermobile participants compared with their nonhypermobile peers was demonstrated (P < .001), whereas no increased risk was found for ankle joint injury. For knee joint injury, a combined odds ratio of 4.69 (95% confidence interval, 1.33-16.52; P = .02) was calculated, indicating a significantly increased risk for hypermobile participants playing contact sports. Conclusion: Sport participants with generalized joint hypermobility have an increased risk of knee joint injury during contact activities but have no altered risk of ankle joint injury.
Persistent Medication Affordability Problems Among Disabled Medicare Beneficiaries After Part D, 2006–2011

Background:Disabled Americans who qualify for Medicare coverage typically have multiple chronic conditions, are highly dependent on effective drug therapy, and have limited financial resources, putting them at risk for cost-related medication nonadherence (CRN). Since 2006, the Part D benefit has helped Medicare beneficiaries afford medications. Objective:To investigate recent national trends in medication affordability among this vulnerable population, stratified by morbidity burden. Design and Subjects:We estimated annual rates of medication affordability among nonelderly disabled participants in a nationally representative survey (2006–2011, n=14,091 person-years) using multivariate logistic regression analyses. Measure:Survey-reported CRN and spending less on other basic needs to afford medicines. Results:In the 6 years following Part D implementation, the proportion of disabled Medicare beneficiaries reporting CRN ranged from 31.6% to 35.6%, while the reported prevalence of spending less on other basic needs to afford medicines ranged from 17.7% to 21.8%. Across study years, those with multiple chronic conditions had consistently worse affordability problems. In 2011, the prevalence of CRN was 37.3% among disabled beneficiaries with ≥3 morbidities as compared with 28.1% among those with fewer morbidities; for spending less on basic needs, the prevalence was 25.4% versus 15.7%, respectively. There were no statistically detectable changes in either measure when comparing 2011 with 2007. Conclusions:Disabled Medicare beneficiaries continue to struggle to afford prescription medications. There is an urgent need for focused policy attention on this vulnerable population, which has inadequate financial access to drug treatments, despite having drug coverage under Medicare Part D.