Antimalarial Drug Combination Predictions Using the Machine Learning Synergy Predictor (MLSyPred©) tool.

PURPOSE: Antimalarial drug resistance is a global public health problem that leads to treatment failure. Synergistic drug combinations can improve treatment outcomes and delay the development of drug resistance. Here, we describe the implementation of a freely available computational tool, Machine Learning Synergy Predictor (MLSyPred©), to predict potential synergy in antimalarial drug combinations. METHODS: The MLSyPred© synergy prediction method extracts molecular fingerprints from the drugs' biochemical structures to use as features and also cleans and prepares the raw data. Five machine learning algorithms (Logistic Regression, Random Forest, Support vector machine, Ada Boost, and Gradient Boost) were implemented to build prediction models. Implementation and application of the MLSyPred© tool were tested using datasets from 1540 combinations of 79 drugs and compounds biologically evaluated in pairs for three strains of Plasmodium falciparum (3D7, HB3, and Dd2). RESULTS: The best prediction models were obtained using Logistic Regression for antimalarials with the strains Dd2 and HB3 (0.81 and 0.70 AUC, respectively) and Random Forest for antimalarials with 3D7 (0.69 AUC). The MLSyPred© tool yielded 45% precision for synergistically predicted antimalarial drug combinations that were annotated and biologically validated, thus confirming the functionality and applicability of the tool. CONCLUSION:  The MLSyPred© tool is freely available and represents a promising strategy for discovering potential synergistic drug combinations for further development as novel antimalarial therapies.

B cells as modulators of HPV+ oropharyngeal cancer in a preclinical model.

Among the different immune cells present within tumors, B cells also infiltrate human papillomavirus-positive (HPV+) oropharyngeal tumors. However, the role of B cells during programmed death-1 (PD-1) blockade in HPV+ oropharyngeal cancer needs to be better defined. By using the preclinical mouse model for HPV+ oropharyngeal cancer (named mEER), we characterized B cells within tumors and determined their functional role in vivo during PD-1 blockade. We determined that treatment naïve tongue-implanted tumors, which we have previously demonstrated to be sensitive to PD-1 blockade, contained high infiltration of CD8+ T cells and low infiltration of B cells whereas flank-implanted tumors, which are resistant to PD-1 blockade, contain a higher frequency of B cells compared to T cells. Moreover, B cell-deficient mice (µMt) and B cell-depleted mice showed a slower tumor growth rate compared to wild-type (WT) mice, and B cell deficiency increased CD8+ T cell infiltration in tumors. When we compared tongue tumor-bearing mice treated with anti-PD-1, we observed that tumors that responded to the therapy contained more T cells and B cells than the ones that did not respond. However, µMt mice treated with PD-1 blockade showed similar tumor growth rates to WT mice. Our data suggest that in untreated mice, B cells have a more pro-tumorigenic phenotype potentially affecting T cell infiltration in the tumors. In contrast, B cells are dispensable for PD-1 blockade efficacy. Mechanistic studies are needed to identify novel targets to promote the anti-tumorigenic function and/or suppress the immunosuppressive function of B cells in HPV+ oropharyngeal cancer.

Poly(vinyl alcohol)/Silk Fibroin/Ag-NPs Composite Nanofibers as a Substrate for MG-63 Cells' Growth.

Nanofiber scaffolds of polyvinyl alcohol, silk fibroin from Bombyx mori cocoons, and silver nanoparticles were developed as a substrate for MG-63 growth. The fiber morphology, mechanical properties, thermal degradation, chemical composition, and water contact angle were investigated. In vitro tests were performed by the cell viability MTS test of MG-63 cells on electrospun PVA scaffolds, mineralization was analyzed by alizarin red, and the alkaline phosphatase (ALP) assay was evaluated. At higher PVA concentrations, Young's modulus (E) increased. The addition of fibroin and silver nanoparticles improved the thermal stability of PVA scaffolds. FTIR spectra indicated characteristic absorption peaks related to the chemical structures of PVA, fibroin, and Ag-NPs, demonstrating good interactions between them. The contact angle of the PVA scaffolds decreased with the incorporation of fibroin and showed hydrophilic characteristics. In all concentrations, MG-63 cells on PVA/fibroin/Ag-NPs scaffolds had higher cell viability than PVA pristine. On day ten of culture, PVA18/SF/Ag-NPs showed the highest mineralization, observed by the alizarin red test. PVA10/SF/Ag-NPs presented the highest alkaline phosphatase activity after an incubation time of 37 h. The achievements indicate the potential of the nanofibers of PVA18/SF/Ag-NPs as a possible substitute for bone tissue engineering (BTE).

Electromyographic Examination of Hip and Knee Extension Hex Bar Exercises Varied by Starting Knee and Torso Angles.

Variations of the deadlift can be executed using the hexagonal (hex) bar by altering, for instance, the knee and torso angles while maintaining a constant hip angle at the start position. PURPOSE: To examine muscle activation patterns of the biceps femoris, rectus femoris, and erector spinae during three deadlift variations using the hex bar. METHODS: Twenty resistance-trained male and female subjects performed hex bar deadlift variations in three different starting knee flexion positions: 128.4 ± 8.5°, 111.9 ± 8.7°, and 98.3 ± 6.5°. Subjects performed three repetitions at 75% of their three-repetition maximum. Electromyography sensors were placed on the dominant biceps femoris, rectus femoris, and lumbar erector spinae. A one-way repeated measures ANOVA was used to detect differences in mean and peak EMG values normalized to maximum voluntary isometric contraction (MVIC) (p < 0.05). RESULTS: As knee flexion increased at the starting position, mean activation of the rectus femoris increased (24.7 ± 21.5 → 35.5 ± 25.4 → 62.1 ± 31.3% MVIC, p < 0.001), while biceps femoris (40.6 ± 17.9 → 34.0 ± 16.4 → 28.1 ± 14.5% MVIC, p = 0.003) and erector spinae (73.0 ± 27.6 → 65.9 ± 34.4 → 54.9 ± 32.5% MVIC, p = 0.009) activation decreased. Peak activation of the rectus femoris increased (46.9 ± 33.0 → 60.9 ± 38.7 → 99.3 ± 41.6% MVIC, p < 0.001) while decreasing in the erector spinae (118.6 ± 47.1 → 105.9 ± 49.4 → 89.1 ± 40.1% MVIC, p = 0.008). The rectus femoris experienced the greatest mean differences of the three muscles. CONCLUSIONS: Practitioners should consider the muscular goals when adjusting the starting position of a hex bar deadlift as posterior chain recruitment diminished and quadriceps activation increased as knee flexion increased.

An Update of Peer Support/Peer Provided Services Underlying Processes, Benefits, and Critical Ingredients.

The purpose of this article is to delineate the current state-of-the-knowledge of peer support following the framework employed in the 2004 article (Solomon, Psychiatr Rehabil J. 2004;27(4):392-401 1). A scoping literature was conducted and included articles from 1980 to present. Since 2004, major growth and advancements in peer support have occurred from the development of new specializations to training, certification, reimbursement mechanisms, competency standards and fidelity assessment. Peer support is now a service offered across the world and considered an indispensable mental health service. As the field continues to evolve and develop, peer support is emerging as a standard of practice throughout various, diverse settings and shows potential to impact clinical outcomes for service users throughout the globe. While these efforts have enhanced the professionalism of the peer workforce, hopefully this has enhanced the positive elements of these services and not diluted them.

Creation of Formalin-Fixed, Paraffin-Embedded 3D Lung Cancer Cellular Spheroids for the Optimization of Immunohistochemistry Staining Procedures.

In an era of precision medicine important treatment decisions are dictated by expression of clinically informative tumor protein biomarkers. These biomarkers can be detected by immunohistochemistry (IHC) performed in tumor tissue sections obtained from biopsies or resections. Like all experimental procedures, IHC needs optimization for several of its steps. However, the investigator must avoid optimizing the IHC procedure using valuable human biopsy samples which may be difficult to obtain. Ideally, valuable biopsy samples should only be subjected to IHC once the IHC protocol has been optimized. In this chapter, we describe a procedure for IHC optimization using tri-dimensional (3D) cellular spheroids created from cultured cells. In this approach, cultured cells are pelleted into 3D spheroids, which are then processed just like a tissue sample, namely, fixed, embedded, sectioned, mounted on slides, and stained with IHC just like a human tissue sample. These 3D cellular spheroids have a tissue-like architecture and cellularity resembling a tumor section, and both cellular and antigen structure are preserved. This method is therefore acceptable for IHC optimization before proceeding to the IHC staining of human tumor samples.

Immunoblot Validation of Phospho-Specific Antibodies Using Lung Cancer Cell Lines.

The cancer phenotype is usually characterized by deregulated activity of a variety of cellular kinases, with consequent abnormal hyper-phosphorylation of their target proteins. Therefore, antibodies that allow the detection of phosphorylated versions of proteins have become important tools both preclinically in molecular cancer research, and at the clinical level by serving as tools in pathological analyses of tumors. In order to ensure reliable results, validation of the phospho-specificity of these antibodies is extremely important, since this ensures that they are indeed able to discriminate between the phosphorylated and unphosphorylated versions of the protein of interest, specifically recognizing the phosphorylated variant. A recommended validation approach consists in dephosphorylating the target protein and assessing if such dephosphorylation abrogates antigen immunoreactivity when using the phospho-specific antibody. In this chapter, we describe a protocol to validate the specificity of a phospho-specific antibody that recognizes a phosphorylated variant of the Retinoblastoma (Rb) protein in lung cancer cell lines. The protocol consists in the dephosphorylation of the Rb-containing protein lysates by treating them with bovine intestinal phosphatase, followed by assessment of the dephosphorylation by immunoblot.

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy.

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer's disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562.

Peer and Non-Peer Academic Scientists and Peer Support Specialist Community of Practice: Stakeholder Engagement to Advance the Science of Peer Support.

Community of Practice, a community-engagement method that encourages a group of people to interact regularly towards a common goal, may promote satisfying experiences in patient-outcomes research among marginalized populations. Peer support specialists are increasingly being involved in peer-informed mental health research due to their lived experiences of mental illness and are an asset in co-designing healthcare programs along with researchers. In 2015, ten scientists and ten mental health service users joined as a Community of Practice that trained to engage in patient-centered outcomes research. The group has so far has presented at 20 conferences, published three book chapters and 30 peer-reviewed publications, and developed two smartphone applications. Of note are the co-production of a smartphone application, a digital peer support certification program, an app decision support tool, and an instrument to assess the value of patient-research partnerships. Future research will assess the feasibility of incorporating more stakeholders to enhance research outcomes.

Venom characterization of the bark scorpion Centruroides edwardsii (Gervais 1843): Composition, biochemical activities and in vivo toxicity for potential prey.

In this study, we characterize the venom of Centruroides edwardsii, one of the most abundant scorpions in urban and rural areas of Costa Rica, in terms of its biochemical constituents and their biological activities. C. edwardsii venom is rich in peptides but also contains some higher molecular weight protein components. No phospholipase A2, hemolytic or fibrinogenolytic activities were found, but the presence of proteolytic and hyaluronidase enzymes was evidenced by zymography. Venom proteomic analysis indicates the presence of a hyaluronidase, several cysteine-rich secretory proteins, metalloproteinases and a peptidylglycine α-hydroxylating monooxygenase like-enzyme. It also includes peptides similar to the K+-channel blocker margatoxin, a dominant toxin in the venom of the related scorpion C. margaritatus. MS and N-terminal sequencing analysis also reveals the presence of Na+-channel-modulating peptides with sequence similarity to orthologs present in other scorpion species of the genera Centruroides and Tityus. We purified the hyaluronidase (which co-eluted with an allergen 5-like CRiSP) and sequenced ~60% of this enzyme. We also sequenced some venom gland transcripts that include other cysteine-containing peptides and a Non-Disulfide Bridged Peptide (NDBP). Our in vivo experiments characterizing the effects on potential predators and prey show that C. edwardsii venom induces paralysis in several species of arthropods and geckos; crickets being the most sensitive and cockroaches and scorpions the most resistant organisms tested. Envenomation signs were also observed in mice, but no lethality was reached by intraperitoneal administration of this venom up to 120 µg/g body weight.

Prediabetes, diabetes, and other CVD-related conditions among Asian populations in Los Angeles County, 2014.

Objective: To assess the prevalence of four common health conditions related to cardiovascular disease risk among Asians in Los Angeles County. Methods: A survey of Asians in Los Angeles County was conducted utilizing purposive sampling to recruit from the region's Service Planning Areas 3 and 4; these underserved areas contain high density of Asian populations. Descriptive and multivariable regression analyses were performed to explore and describe potential associations between self-reported diagnoses of prediabetes, diabetes, hypertension, and high cholesterol and body mass index (measured with non-Asian versus Asian cut points) by race/ethnicity (Chinese/Filipino/Korean/Taiwanese/Thai/Vietnamese). Results: The survey response rate was nearly 60%. The analysis included 1,377 Asians, self-identified as either Chinese (n = 700), Filipino (n = 69), Korean (n = 339), Taiwanese (n = 48), Thai (n = 115), or Vietnamese (n = 106). Results showed that, in comparison to other Asians, Filipinos had the highest risks for two of the four conditions described. Other results by subgroup affirmed a similar heterogeneous pattern of Asian health locally. Conclusions: These and other results from the survey point to potential gaps in healthcare needs of Asians, and to opportunities where local public health efforts could help increase these populations' access to cardiovascular disease-related health and social services.

Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

Renal Denervation Reduces Monocyte Activation and Monocyte-Platelet Aggregate Formation: An Anti-Inflammatory Effect Relevant for Cardiovascular Risk.

Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte-platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1ß (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of beneficial cardiovascular effects of RDN.

Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism.

PURPOSE: Early and accurate detection of deep vein thrombosis (DVT) is an important clinical need. Based on the hypothesis that urinary peptides may hold information on DVT in conjunction with pulmonary embolism (PE), the study was aimed at identifying such peptide biomarkers using capillary electrophoresis coupled mass spectrometry. EXPERIMENTAL DESIGN: Patients with symptoms of unprovoked/idiopathic DVT and/or PE were examined by doppler-sonography or angio-computed tomography. Urinary proteome analysis allowed for identification of respective peptide biomarkers. To confirm their biological relevance, we induced PE in mice and assessed human ex vivo thrombi. RESULTS: We identified 62 urinary peptides as DVT-specific biomarkers, i.e. fragments of collagen type I and a fragment of fibrinogen ß-chain. The presence of fibrinogen α/ß in the acute thrombus, and collagen type I and osteopontin in the older, organized thrombus was demonstrated. The classifier DVT62 established through support vector machine (SVM) modeling based on the 62 identified peptides was validated in an independent cohort of 47 subjects (six cases and 41 controls) with a sensitivity of 100% and specificity of 83%. CONCLUSIONS AND CLINICAL RELEVANCE: Urine proteome analysis enabled the detection of DVT-specific peptides, which were validated in human and mouse tissue. Furthermore, it allowed for the establishment of an urinary-proteome based classifier that is relatively specific for DVT. The data provide the basis for assessment of these biomarkers in a prospective clinical study.

PreImplantation factor prevents atherosclerosis via its immunomodulatory effects without affecting serum lipids.

PreImplantation factor (PIF) is a 15-amino acid peptide endogenously secreted by viable embryos, regulating/enabling maternal (host) acceptance/tolerance to the "invading" embryo (allograft) all-while preserving maternal immunity to fight infections. Such attributes make PIF a potential therapeutic agent for chronic inflammatory diseases. We investigated whether PIF's immunomodulatory properties prevent progression of atherosclerosis in the hyper-cholesterolaemic ApoE-deficient murine model. Male, high-fat diet fed, ApoE-deficient (ApoE-/-) mice were administered either PBS, scrambled PIF (0.3-3 mg/kg) or PIF (0.3-3 mg/kg) for seven weeks. After treatment, PIF (3 mg/kg)-treated ApoE-/- mice displayed significantly reduced atherosclerosis lesion burden in the aortic sinus and aortic arch, without any effect on lipid profile. PIF also caused a significant reduction in infiltration of macrophages, decreased expression of pro-inflammatory adhesion molecules, cytokines and chemokines in the plaque, and reduced circulating IFN-γ levels. PIF preferentially binds to monocytes/neutrophils. In vitro, PIF attenuated monocyte migration (MCP-1-induced chemotaxis assay) and in vivo in LPS peritonitis model. Also PIF prevented leukocyte extravasation (peritonitis thioglycollate-induced model), demonstrating that PIF exerts its effect in part by modulation of monocyte function. Inhibition of the potassium channel KCNAB3 (Kv1.3) and of the insulin degrading enzyme (IDE) was demonstrated as potential mechanism of PIF's immunomodulatory effects. In conclusion, PIF regulates/lowers inflammation and prevents atherosclerosis development without affecting circulating lipids. Overall our findings establish PIF as a strong immunomodulatory drug candidate for atherosclerosis therapy.

Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis.

One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads to a decrease in RNA translation. The aberrant tau-ribosome association also impaired synthesis of the synaptic protein PSD-95, suggesting that this phenomenon contributes to synaptic dysfunction. These findings provide novel information about tau-protein interactions in human brains, and they describe, for the first time, a dysfunctional consequence of tau-ribosome associations that directly alters protein synthesis. Significance statement: Despite the identification of abnormal tau-ribosomal interactions in tauopathies >25 years ago, the consequences of this association remained elusive until now. Here, we show that pathological tau associates closely with ribosomes in AD brains, and that this interaction impairs protein synthesis. The overall result is a stark reduction of nascent proteins, including those that participate in synaptic plasticity, which is crucial for learning and memory. These data mechanistically link a common pathologic sign, such as the appearance of pathological tau inside brain cells, with cognitive impairments evident in virtually all tauopathies.

Percepciones de las gestantes en torno al cuidado humanizado por enfermería / Perceptions of pregnant women regarding the nursing human care / Percepções de mulheres gravidas em torno dos cuidados de enfermagem humanizada

Objetivo: determinar las percepciones de comportamiento del cuidado humanizado de enfermería en un grupo de gestantes del servicio de ginecobstetricia de un hospital de alta complejidad del sur-occidente de Colombia, mediante la aplicación de un instrumento, percepciones del cuidado humanizado en enfermería en su primera versión validada por la Universidad Nacional de Colombia. Materiales y Métodos: investigación cuantitativa descriptiva, de corte transversal. La muestra fue de 97 gestantes obtenidos por muestreo no probabilístico por conveniencia, mediante la fórmula para tamaño óptimo cuando la población es conocida. Se tuvo en cuenta las variables sociodemográficas y la percepción de los comportamientos de cuidado humanizado de enfermería. Resultados: el 59 % de las gestantes percibieron el comportamiento del cuidado humanizado como excelente; las categorías con mayor porcentaje fueron características de la enfermera, priorizar al ser de cuidado y proactividad, mientras que las categorías con menor valor fueron empatía, disponibilidad para la atención y dar apoyo emocional. Conclusión: el cuidado humanizado de enfermería, en todas las categorías, fue calificado como bueno y excelente, lo que demuestra una adecuada percepción por parte de las gestantes; sin embargo, es importante fortalecer aspectos relacionados con la empatía y la actitud.

Objective: determine perceptions of behavior of nursing human care in a group of pregnant women from the obstetrics and gynecology service of a high complexity hospital in the south-west of Colombia, through the application of an instrument, perceptions of nursing human care in its first version, validated by the Universidad Nacional de Colombia. Materials and Methods: cross-sectional descriptive quantitative research, the sample was of 97 pregnant women obtained from a non-probabilistic sample by convenience, through the formula for ideal sample size when the population size is known. Social-demographical variables and the perception of behavior of nursing human care were taken in account. Results: 59% of pregnant women perceived the behavior of nursing human care as excellent; the categories with higher percentage were characteristics of the nurse, prioritize the care of the person and proactivity, while the categories with lower percentage were: empathy, attention availability and emotional support. Conclusion: the nursing human care, in all of its categories, was qualified as good and excellent, which demonstrates an adequate perception by the pregnant women; however, it is important to strengthen aspects related to empathy and attitude.

Objetivo: determinar as percepções de comportamento do cuidado humanizado de enfermagem em um grupo de mulheres gravidas do serviço de ginecologia e obstetrícia de um hospital de alta complexidade do Colombia, através da aplicação de um instrumento, "Percepções do cuidado humanizado em enfermagem" em sua primeira versão e validado pela Universidad Nacional de Colombia. Materiais e Métodos: pesquisa quantitativa descritiva, de corte transversal. A amostra foi de 97 mulheres gravidas obtidas por amostragem não probabilística por conveniência, através da fórmula para tamanho óptimo quando a população é conhecida. Foram levadas em conta as variáveis sócio demográficas e a percepção dos comportamentos de cuidado de enfermagem humanizada. Resultados: o 59% das mulheres gravidas perceberam o comportamento do cuidado humanizado como excelente; as categorias com maior porcentagem foram características da enfermeira, priorizar ao ser de cuidado e proatividade, enquanto que as categorias com menor valor foram: empatia, disponibilidade para o atendimento e dar apoio emocional. Conclusão: o cuidado de enfermagem humanizada, em todas as categorias, foi qualificado como bom e excelente, o que demostra uma adequada percepção por parte das mulheres gravidas; no entanto, é importante fortalecer aspectos relacionados com a empatia e a atitude.

Tandem Stenosis to Induce Atherosclerotic Plaque Instability in the Mouse.

Despite the number of animal models of atherosclerosis, a major limitation in research on mechanisms of plaque rupture is the lack of appropriate atherosclerotic mouse models where lesions develop and progress to a vulnerable and thus rupture-prone phenotype that is typically observed in humans. Most animal models of atherosclerosis typically represent a few but not the full combination of the characteristics seen in human unstable/ruptured plaques. Such characteristics most importantly include a thin and ruptured fibrous cap, plaque inflammation, neovascularization within the plaque (vasa vasorum), plaque hemorrhage, and intravascular (often occlusive) thrombus formation. Ideally, an animal model of plaque instability/rupture would respond to current pharmacological interventions known to reduce the risk of plaque rupture, such as statins. Here we describe a mouse model of plaque instability/rupture that is based on the surgical introduction of a tandem stenosis in the carotid artery. This model results in the formation of unstable atherosclerotic plaques that reflect human plaque pathology. It will allow to further understanding of plaque instability/rupture, to identify the participating factors such as specific proteins, genes and microRNAs, and to develop imaging methods towards the detection of vulnerable, rupture-prone atherosclerotic plaques.