Miracle-dz/UniFAR-FTUs huggingface dataset:
Prótese vascular derivada do látex

BACKGROUND: The development of vascular grafts has been crucial for advances and achievements in reconstructive vascular surgery over the past 5 decades. OBJECTIVES: To develop a new model of microperforated vascular graft using fabric covered with a natural latex-derived polymer taken from Hevea brasiliensis and assess its patency, thrombogenicity, biocompatibility and healing process, besides some mechanical properties (adaptability, elasticity, impermeability and possibility of suture), using expanded polytetrafluoroethylene graft as control. METHODS: Fifteen dogs were divided into three groups of five animals. The microperforated latex graft was implanted in all dogs and the expanded polytetrafluoroethylene graft was implanted in the contralateral pelvic limb. Postoperative follow-up was 4, 8 and 12 weeks. Analysis of results was performed according to clinical evaluation of pulses, complications (fluid collection, dehiscence, granuloma and infection), arteriography, macroscopic analysis and scanning electron micrography. RESULTS: Statistical tests revealed no significant differences (p > 0.05) concerning post-operative complications and graft patency. Both grafts were properly integrated to surrounding tissues, with connective tissue formed by collagen fibers. A neointimal layer covering all extension of the luminal surface was observed in the microperforated latex graft. Conversely, the endothelial development over the neointimal surface was limited to regions adjacent to the anastomoses in the expanded polytetrafluoroethylene graft. CONCLUSIONS: The microperforated latex graft showed satisfactory structural qualities (adaptability, elasticity, impermeability and possibility of suture) as a vascular substitute. It stimulated endothelial growth beyond contact regions with the artery in anastomoses and was biocompatible in the dog's arterial system, presenting adequate tissue integration.
Polo‐like kinase 2 is a mediator of hedgehog survival signaling in cholangiocarcinoma

Cholangiocarcinoma (CCA) cells paradoxically express the death ligand tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and thus rely on potent survival signals to circumvent cell death by TRAIL. Hedgehog (Hh) signaling is an important survival pathway in CCA. Herein, we further examine the mechanisms whereby Hh signaling mediates apoptosis resistance in CCA, revealing a pivotal role for the cell division regulating serine/threonine kinase polo‐like kinase 2 (PLK2). We employed 50 human CCA samples (25 intrahepatic and 25 extrahepatic CCA) as well as human KMCH‐1, Mz‐CHA‐1, and HUCCT‐1 CCA cells for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. In human samples, polo‐like kinase (PLK)1/2/3‐immunoreactive cancer cells were present in the preponderance of intra‐ and extrahepatic CCA specimens. Inhibition of Hh signaling by cyclopamine reduced PLK2, but not PLK1 or PLK3, messenger RNA and protein expression in vehicle‐treated and sonic Hh–treated CCA cells, confirming our previous microarray study. PLK2 regulation by Hh signaling appears to be direct, because the Hh transcription factors, glioma‐associated oncogene 1 and 2, bind to the PLK2 promotor. Moreover, inhibition of PLK2 by the PLK inhibitor, BI 6727 (volasertib), or PLK2 knockdown was proapoptotic in CCA cells. BI 6727 administration or PLK2 knockdown decreased cellular protein levels of antiapoptotic myeloid cell leukemia 1 (Mcl‐1), an effect reversed by the proteasome inhibitor, MG‐132. Finally, BI 6727 administration reduced Mcl‐1 protein expression in CCA cells, resulting in CCA cell apoptosis and tumor suppression in vivo. Conclusion: PLK2 appears to be an important mediator of Hh survival signaling. These results suggest PLK inhibitors to be of therapeutic value for treatment of human CCA. (Hepatology 2013;58:1362–1374)
Prevalence, Characteristics and Outcomes of People Aged 65 Years and Over with an Incidental Rise in Cardiac Troponin I

Background: Cardiac troponin I (cTnI) is a sensitive and specific marker of acute cardiac damage. We examined the prevalence, characteristics and outcome of incidental cTnI rises in older patients. Methods: One hundred and eighty-seven consecutive patients aged 65 years or over with a raised cTnI on admission at least 8 h after symptom onset were categorised into: (1) ST-elevation myocardial infarction, (2) other acute coronary syndromes (ACS), (3) other recognised non-ACS causes of cTnI rise and (4) non-ACS with no other identifiable cause (an incidental finding). The number of readmissions and deaths for each group was measured at 30 and 90 days. Results: Age range = 65–98 years. Male = 55.6%. Fifty-four percent had a raised cTnI due to non-ACS illnesses, whilst in 18% it was an incidental finding. The latter group was relatively older and had a significantly lower degree of cTnI rise (U = 1718.5, p = 0.002), but a higher readmission and mortality rate compared to the other groups (categories 1–3) for both follow-up periods. Conclusions: Incidental cTnI rise is common in older patients and is associated with a poorer prognosis compared to ACS or a recognised non-ACS condition. Future research should attempt to evaluate the significance of such incidental rises in elderly patients.
Epigenetic regulation of MicroRNA‐122 by peroxisome proliferator activated receptor‐gamma and hepatitis b virus X protein in hepatocellular carcinoma cells

MicroRNA‐122 (miR‐122), a pivotal liver‐specific miRNA, has been implicated in several liver diseases including hepatocellular carcinoma (HCC) and hepatitis C and B viral infection. This study aimed to explore epigenetic regulation of miR‐122 in human HCC cells and to examine the effect of hepatitis C virus (HCV) and hepatitis B virus (HBV). We performed microRNA microarray analysis and identified miR‐122 as the most up‐regulated miRNA (6‐fold) in human HCC cells treated with 5′aza‐2′deoxycytidine (5‐Aza‐CdR, DNA methylation inhibitor) and 4‐phenylbutyric acid (PBA, histone deacetylation inhibitor). Real‐time polymerase chain reaction (PCR) analysis verified significant up‐regulation of miR‐122 by 5′aza and PBA in HCC cells, and to a lesser extent in primary hepatocytes. Peroxisome proliferator activated receptor‐gamma (PPARγ) and retinoid X receptor alpha (RXRα) complex was found to be associated with the DR1 and DR2 consensus site in the miR‐122 gene promoter which enhanced miR‐122 gene transcription. 5‐Aza‐CdR and PBA treatment increased the association of PPARγ/RXRα, but decreased the association of its corepressors (N‐CoR and SMRT), with the miR‐122 DR1 and DR2 motifs. The aforementioned DNA‐protein complex also contains SUV39H1, an H3K9 histone methyl transferase, which down‐regulates miR‐122 expression. Conclusions: These findings establish a novel role of the PPARγ binding complex for epigenetic regulation of miR‐122 in human HCC cells. Moreover, we show that hepatitis B virus X protein binds PPARγ and inhibits the transcription of miR‐122, whereas hepatitis C viral particles exhibited no significant effect; these findings provide mechanistic insight into reduction of miR‐122 in patients with HBV but not with HCV infection. (Hepatology 2013;58:1681–1692)
Tdap: a new option for pertussis booster vaccination of seniors

Pertussis or whooping cough, caused by Bordetella pertussis, remains a global concern. Following the availability of vaccines against pertussis from the mid-1940s, the reported pertussis incidence rate fell dramatically in countries with high vaccine coverage. However, countries with long-standing high pertussis vaccine coverage have, since the 1980s, increasingly identified pertussis in adolescents and adults. In adults ≥65 years of age, there is less data on morbidity but outbreaks in settings such as residential facilities have been associated with severe morbidity including death. The US FDA approved two different tetanus, diphtheria and pertussis vaccines in 2005 for booster vaccination of adolescents and adults, extending usage to adults 18–64 years of age in 2008. Following data demonstrating satisfactory immunogenicity, the FDA approved a single dose of tetanus, diphtheria and pertussis vaccine for use in adults 65 years or older in July 2011. This review will discuss the available data on the dis.
Are Nursing Faculty Ready to Integrate Genomic Content Into Curricula?

Genomics is an emerging field with newly developed expectations for all healthcare professionals. Nursing faculty are critical to preparing the future nursing workforce in genomics but faculty knowledge, receptivity, and interest in learning more about this subject were unknown. The authors discuss the process used to assess nursing faculty’s readiness to change as a way to substantiate the need for faculty training.
Beyond Google Docs

With this article, Dr Diane Wink’s long-running authorship of this department comes to an end. Diane made a significant contribution to the journal; her articles were always interesting and informative, helping to advance our thinking. Thank you, Diane! Your department articles will be missed. Suzanne P. Smith, EdD, RN, FAAN, Editor-in-Chief Many course management systems lack the social atmosphere and interactivity of face-to-face classrooms that are essential for developing communication and collaborative skills in nursing students. Creating a sense of community online not only facilitates collaboration but also increases student satisfaction and perceived learning. In this article, the authors describe free Google tools that faculty can use to foster communication and collaboration among students in online, blended, and face-to-face learning environments.
Growth and development of a new subspecialty: Pediatric hepatology

Several major forces converged to catalyze the formal emergence of a body of knowledge and an organized focus on disorders of the liver in early life. Attendant to the development of a focused clinical subspecialty the pace of patient‐ and laboratory‐based research in the field quickened in parallel to decipher the consequences of genetic or metabolic aberrations on immature liver structure and function. The key research observations that catalyzed the emergence and subsequent rapid growth of Pediatric Hepatology include: (1) an understanding of the dynamic events occurring during hepatobiliary development and the importance of these physiologic variables that occur during liver maturation; (2) the recognition of the unique nature of inherited and acquired liver diseases that affect infants and children—such as biliary atresia and Reye's syndrome; and (3) redefinition of the once obscure inherited intrahepatic cholestatic diseases of the liver, which, in turn, provided insight into normal and abnormal hepatobiliary physiology. The clinical advances were highlighted by the development of specific approaches to the diagnosis and management of liver disease in infants and children, including both liver transplantation and nontransplant treatment options. These seminal events led to the expansion of the workforce, creating a critical mass consisting of individuals with focused, specialized skills and techniques. In‐depth expertise allowed more accurate diagnosis and highly effective treatment strategies for advanced hepatobiliary disease in children. The demand for pediatric clinicians with experience in advanced hepatology allowed sub‐sub‐specialization to flourish. Continued maturation of the field led to definition of hepatology‐focused curricular elements and educational content for Pediatric Gastroenterology training programs, and subsequently the development of program requirements for those who wished to acquire additional training in Pediatric Hepatology. A significant rite of passage was marked by the election of pediatric hepatologists to leadership positions in the American Association for the Study of Liver Diseases (AASLD). Further validation of the field occurred with approval of the petition for establishing a Certificate of Added Qualification in Transplant Hepatology by the American Board of Pediatrics. Here I relate my perspective on the history of the advances in our field and the contributions of many of the clinicians and scientists whose efforts led to the development of focused clinical, research, and training programs that improved the care of children with diseases of the liver. (Hepatology 2013;58:458‐476)
ranscranial direct current stimulation over the supplementary motor rea modulates the preparatory activation level in the human motor ystem nthony

Transcranial direct current stimulation (tDCS) is a non-invasive stimulation method that can induce transient polarity-specific neuroplastic changes in cortical excitability lasting up to 1 h post-stimulation. While excitability changes with stimulation over the primary motor cortex have been well documented, the functional effects of stimulation over premotor regions are less well understood. In the present experiment, we tested how cathodal and anodal tDCS applied over the region of the supplementary motor area (SMA) affected preparation and initiation of a voluntary movement. Participants performed a simple reaction time (RT) task requiring a targeted wrist-extension in response to a go-signal. In 20% of RT trials a startling acoustic stimulus (SAS) was presented 500 ms prior to the “go” signal in order to probe the state of motor preparation. Following the application of cathodal, anodal, or sham tDCS (separate days) over SMA for 10 min, participants performed blocks of RT trials at 10 min intervals. While sham stimulation did not affect RT or incidence of early release by the SAS, cathodal tDCS led to a significant slowing of RT eural activation that peaked 10 min after the end of stimulation and was associated with a marked decrease in the incidence of movement release by the SAS. In contrast, anodal tDCS resulted in faster RTs, but the incidence of release was unchanged. These results are consistent with the SMA playing a role in the pre-planning of movements and that modulating its activity with tDCS can lead to polarity-specific changes in motor behavior.
The Age-Related Performance Decline in Ultraendurance Mountain Biking

The age-related changes in ultraendurance performance have been previously examined for running and triathlon but not mountain biking. The aims of this study were (i) to describe the performance trends and (ii) to analyze the age-related performance decline in ultraendurance mountain biking in a 120-km ultraendurance mountain bike race the “Swiss Bike Masters” from 1995 to 2009 in 9,325 male athletes. The mean (±SD) race time decreased from 590 ± 80 min to 529 ± 88 min for overall finishers and from 415 ± 8 min to 359 ± 16 min for the top 10 finishers, respectively. The mean (±SD) age of all finishers significantly (P < 0.001) increased from 31.6 ± 6.5 years to 37.9 ± 8.9 years, while the age of the top 10 remained stable at 30.0 ± 1.6 years. The race time of mountain bikers aged between 25 and 34 years was significantly (P < 0.01) faster compared with the race time of older age groups. The age-related decline in performance in endurance mountain bikers in the “Swiss Bike Masters” appears to start earlier compared with other ultraendurance sports.
Cyber-Bullying and Incivility in an Online Learning Environment, Part 2: Promoting Student Success in the Virtual Classroom

The appeal of online learning has increased dramatically among nurses who are pursuing higher-education opportunities. However, online learning has created potential avenues for uncivil behaviors that can affect student satisfaction, performance, and retention. This is the second of 2 articles detailing a study to empirically measure nursing faculty and student perceptions of an online learning environment (OLE). Part 1, in the July/August 2012 issue, described the quantitative results including the types and frequency of uncivil behaviors and the extent to which they are perceived to be a problem in online courses. In this portion of the study, the authors discuss the qualitative findings, including the challenges and advantages of the OLE, specific ways to foster civility, and strategies to promote student success and retention.
Surface Electromyographic Activities of Upper Body Muscles during High-intensity Cycle Ergometry

The aim of this study was to investigate upper body muscle activity during a 30 s Wingate test. Eighteen physically active participants performed a Wingate test while muscle activity was recorded from the brachioradialis (BR), biceps brachii (BB), triceps brachii (TB) and upper trapezius (UT). Measurements were obtained at rest, during a function maximal contraction (FMC) and during the 30 s Wingate test, whilst participants were positioned in a seated position on the cycle ergometer. All muscles were significantly active for the duration of the test. When normalized as a %FMC no differences in activity were found between muscles. Across the 30 s, power output was found to significantly decrease, whereas no changes were found in upper body muscle activity. All muscles investigated were active during the Wingate test and therefore confirmed previous findings that the upper body significantly contributes to power profiles obtained during high intensity cycle ergometry in addition to its role in stabilizing the body.
Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice

Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration. Survivin, a member of the family of inhibitor of apoptosis proteins (IAPs), plays key roles in the proliferation and apoptosis of various cell types. Here, we characterized the in vivo function of Survivin in regulating postnatal liver development and homeostasis using mice carrying conditional Survivin alleles. Hepatic perinatal loss of Survivin causes impaired mitosis, increased genome ploidy, and enlarged cell size in postnatal livers, which eventually leads to hepatocyte apoptosis and triggers tissue damage and inflammation. Subsequently, HPCs that retain genomic Survivin alleles are activated, which finally differentiate into hepatocytes and reconstitute the whole liver. By contrast, inducible ablation of Survivin in adult hepatocytes does not affect HPC activation and liver homeostasis during a long‐life period. Conclusion: Perinatal Survivin deletion impairs hepatic mitosis in postnatal liver development, which induces HPC activation and reconstitution in the liver, therefore providing a novel HPC induction model. (Hepatology 2013; 58:2109–2121)
MicroRNA/gene profiling unveils early molecular changes and nuclear factor erythroid related factor 2 (NRF2) activation in a rat model recapitulating human hepatocellular carcinoma (HCC)

Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then used to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the resistant‐hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin‐19, indicating that several HCC‐associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene‐target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the nuclear factor erythroid related factor 2 (NRF2) pathway and up‐regulation of the miR‐200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR‐200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3‐induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin‐19‐positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated with human HCC as well underlines the translational value of our results. Conclusion: This study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target. (Hepatology 2014;58:228–241)
Expression of Metallothionein in Node‐Negative Breast Cancer Correlates with Poor Prognosis

Abstract: Metallothionein (MT) is a cysteine‐rich protein that binds metals and is present in a number of normal cells, mainly during fetal life. It has been suggested that the developmental profile of metallothionein is similar to oncofetal gene products, and therefore, it could be potentially used as a prognostic tumor marker. We explored this concept by performing immuno‐histochemical stain for metallothionein in 155 axillary lymph node‐negative breast carcinomas. Traditional tumor prognosticators of breast cancer including histologic type, nuclear grade, and estrogen receptor content were also analyzed to determine whether or not metallothionein is an independent marker of behavior. Moderate to strong metallothionein immunoreactivity of tumor cells correlated with decreased disease free (p < 0.02), and overall survivals (p < 0.03). No correlation was found between MT and histologic type and nuclear grade of tumors. Similarly, there was no statistically significant relationship between MT and estrogen receptor contents. It is concluded that overexpression of metallothionein is an independent indicator of poor prognosis in node‐negative breast carcinomas.
Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor

The new standard of care for treatment‐naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients. Treatment‐naïve, noncirrhosis patients infected with genotype‐1 HCV and a low viral load at baseline were considered for inclusion (n = 233). After 4 weeks of lead‐in therapy with peginterferon α‐2b and ribavirin, 101 patients (48%) had a rapid virologic response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and were eligible to participate. Patients were randomized 1:1 to 20 weeks of additional therapy with peginterferon α‐2b and ribavirin (double therapy) or to 24 weeks of peginterferon α‐2b, ribavirin, and boceprevir (triple therapy). There was no significant difference in rates of SVR‐12 in patients treated with double versus triple therapy. This similarity persisted regardless of viral subtype (genotype 1a or 1b), interleukin (IL)−28b genotype (CC or non‐CC), or ethnicity (African American versus non‐Hispanic white). Conclusion: Protease inhibitor therapy could be obviated in genotype 1‐infected treatment‐naïve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin. (Hepatology 2014;58:71–77)