Calcineurin activity in Fonsecaea pedrosoi: tacrolimus and cyclosporine A inhibited conidia growth, filamentation and showed synergism with itraconazole.

Fonsecaea pedrosoi is a melanized fungus that causes chromoblastomycosis (CBM), a tropical neglected disease responsible for chronic and disability-related subcutaneous mycosis. Given the challenging nature of CBM treatment, the study of new targets and novel bioactive drugs capable of improving patient life quality is urgent. In the present work, we detected a calcineurin activity in F. pedrosoi conidial form, employing primarily colorimetric, immunoblotting and flow cytometry assays. Our findings reveal that the calcineurin activity of F. pedrosoi was stimulated by Ca2+/calmodulin, inhibited by EGTA and specific inhibitors, such as tacrolimus (FK506) and cyclosporine A (CsA), and proved to be insensitive to okadaic acid. In addition, FK506 and CsA were able to affect the cellular viability and the fungal proliferation. This effect was corroborated by transmission electron microscopy that showed both calcineurin inhibitors promoted profound changes in the ultrastructure of conidia, causing mainly cytoplasm condensation and intense vacuolization that are clear indication of cell death. Our data indicated that FK506 exhibited the highest effectiveness, with a minimum inhibitory concentration (MIC) of 3.12 mg/L, whereas CsA required 15.6 mg/L to inhibit 100% of conidial growth. Interestingly, when both were combined with itraconazole, they demonstrated anti-F. pedrosoi activity, exhibiting a synergistic effect. Moreover, the fungal filamentation was affected after treatment with both calcineurin inhibitors. These data corroborate with other calcineurin studies in fungal cells and open up further discussions aiming to establish the role of this enzyme as a potential target for antifungal therapy against CBM infections.

Effects of the natural antimicrobial peptide aureocin A53 on cells of Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis in the excised teat model.

Aureocin A53 is an N-formylated antimicrobial peptide (AMP) produced by Staphylococcus aureus. Aureocin A53 has a broad spectrum of antimicrobial activity against human and animal pathogens. In the present study, its antagonistic activity was investigated towards 30 strains of S. aureus and 30 strains of Streptococcus spp. isolated from bovine mastitis cases in Brazil. Bovine mastitis is a disease that causes a major economic impact worldwide. Aureocin A53 inhibited the growth of all 60 strains tested, including multidrug-resistant streptococcal isolates and strains of S. aureus belonging to different pulsotypes. This AMP proved to be bactericidal against the six target strains randomly selected among staphylococci and streptococci, also exhibiting a lytic mode of action against the staphylococcal cells. Furthermore, it was determined that 2,048 AU/mL of the AMP were required to inhibit 99.99% of the cell growth of the strain less sensitive to aureocin A53. Aureocin A53 was not toxic to bovine mammary gland epithelial cells after a 24-h exposure and maintained its antimicrobial activity when tested in the excised-teat model against strains of S. aureus and Streptococcus agalactiae, the species responsible for most intramammary infections, not only in Brazil but in other countries as well. Therefore, the use of aureocin A53 in the development of new pharmacological products for the prophylaxis and/or treatment of bovine mastitis was considered promising.

The flavonoid kaempferol protects the fruit fly Drosophila melanogaster against the motor impairment produced by exposure to the insecticide fipronil.

Exposure to pesticides across species has been associated with cognitive and motor impairments. As the problem impacts ecosystem stability, food production and public health, it is urgent to develop multifactorial solutions, from regulatory legislation to pharmacological alternatives that ameliorate the impairments. Fipronil, a commonly used insecticide, acts as a GABAA receptor (GABAAR) antagonist and induces motor impairments in vertebrates and invertebrates. Here, we hypothesized that kaempferol, a secondary metabolite derived from plants, acting as an allosteric modulator of GABAARs, would protect against the negative effects induced by the administration of fipronil in adults of the fruit fly Drosophila melanogaster. We further evaluated our hypothesis via co-administration of flumazenil, a competitive antagonist on the GABAAR, and through in silico analyses. We administered kaempferol prophylactically at three concentrations (10, 30 and 50 µmol l-1) and evaluated its protective effects against motor impairments induced by fipronil. We then used a single dose of kaempferol (50 µmol l-1) to evaluate its protective effect while administering flumazenil. We found that oral administration of fipronil impaired motor control and walking ability. In contrast, kaempferol was innocuous and protected flies from developing the motor-impaired phenotype, whereas the co-administration of flumazenil counteracted these protective effects. These results are supported by the binding of the ligands with the receptor. Together, our results suggest that kaempferol exerts a protective effect against fipronil via positive allosteric modulation of GABAARs, probably within brain areas such as the central complex and the mushroom bodies. These findings further support current attempts to use metabolites derived from plants as protectors against impairments produced by pesticides.

Suprahepatic Cava Thrombus Due to Wilms Tumor: Technique Without Cardiopulmonary Bypass.

Wilms tumor is a frequent malignant neoplasia in pediatric population. Extension to the inferior vena cava is a complication that occurs in approximately 4%-15% of cases. Surgical techniques derived from the field of adult transplant surgery allow the resection of the tumor with its thrombus extension. In the case of a 6-year-old male patient with a stage III Wilms tumor that originated from the left renal vein, thrombectomy and left radical nephroureterectomy were accomplished without extracorporeal circulation. Surgical technique applied in adult transplant surgery for removal of advanced renal tumors, could be a safe and feasible technique in pediatric population.

Plasma Rico em Plaquetas na Cicatrização de Úlcera Venosa: Relato de Caso / Platelet-rich Plasma in Venous Ulcer Healing: Case Report / Plasma Rico en Plaquetas en la Cicatrización de Úlceras Venosas: Informe de un Caso

Objetivo:Avaliar a evolução da reparação tecidual de úlcera venosa (UV) tratada com plasma rico em plaquetas (PRP). Métodos: Trata-se de relato de caso com aplicação de PRP para tratamento de UV em uma clínica especializada de uma cidade do sul de Minas Gerais. A cada sessão foram coletados 20 mL de sangue distribuídos em quatro tubos com citrato de sódio. O sangue passou por centrifugação para a extração do PRP. O plasma foi aplicado na ferida após a limpeza com água destilada e solução de polihexametileno biguanida. Posteriormente, a lesão foi coberta com gazes impregnada com petrolato e gazes estéreis como cobertura secundária, associado à terapia compressiva elástica. Resultados: Anteriormente à terapia, a úlcera apresentava 1,18 cm² de área. Após quatro semanas de tratamento com PRP, ocorreu a completa cicatrização. Conclusão: O tratamento mostrou-se eficaz e houve 100% de redução de área.

Objective:To evaluate the evolution of tissue repair in venous ulcers treated with platelet-rich plasma. Methods: This is a case report with the application of platelet-rich plasma for the treatment of venous ulcers in a specialized clinic in a city in the south of Minas Gerais. At each session, 20 mL of blood was collected and distributed into four tubes with sodium citrate. The blood was centrifuged to extract platelet-rich plasma. Plasma was applied to the wound after cleaning with distilled water and polyhexamethylene biguanide solution. Subsequently, the lesion was covered with gauze impregnated with petrolatum and sterile gauze as a secondary coverage, associated with elastic compression therapy. Results: Prior to therapy, the ulcer had an area of 1.18 cm². After five weeks of treatment with platelet-rich plasma, complete healing has occurred. Conclusion: Tissue repair occurred after five weeks of treatment without any complications.

Objetivo:Evaluar la evolución de la reparación tisular en úlceras venosas tratadas con plasma rico en plaquetas. Métodos: Este es un reporte de caso con la aplicación de plasma rico en plaquetas para el tratamiento de úlceras venosas en una clínica especializada en una ciudad del sur de Minas Gerais. En cada sesión se recogieron 20 ml de sangre y se distribuyeron en cuatro tubos con citrato de sodio. La sangre se centrifugó para extraer plasma rico en plaquetas. Se aplicó plasma a la herida después de limpiarla con agua destilada y solución de polihexametileno biguanida. Posteriormente se cubrió la lesión con gasa impregnada de vaselina y gasa estéril como cobertura secundaria, asociada a terapia compresiva elástica. Resultados: Inicialmente la terapia, la úlcera tenía un área de 1,18 cm². Después de cinco semanas de tratamiento con plasma rico en plaquetas, se produjo una curación completa. Conclusión: La reparación del tejido ocurrió después de cinco semanas de tratamiento sin ninguna complicación.

Oxytetracycline and Streptomycin Resistance Genes in Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot in Peach.

Xanthomonas arboricola pv. pruni (Xap) causes bacterial spot, a major worldwide disease of Prunus species. Very few chemical management options are available for this disease and frequent applications of oxytetracycline (OTC) in the United States peach orchards have raised concerns about resistance development. During 2017-2020, 430 Xap strains were collected from ten peach orchards in South Carolina. Seven OTC-resistant (OTC R ) Xap strains were found in 2017 and 2020 from four orchards about 20-270 km apart. Interestingly, the seven strains were also resistant to streptomycin (STR). Six strains grew on media amended with ≤100 µg/mL OTC, while one strain, R1, grew on ≤250 µg/mL OTC. Genome sequence analysis of four representative OTC R strains revealed a 14-20 kb plasmid carrying tetC, tetR, and strAB in each strain. These three genes were transferable to Xanthomonas perforans via conjugation, and they were PCR confirmed in all seven OTC R Xap strains. When tetC and tetR were cloned and expressed together in a sensitive strain, the transconjugants showed resistance to ≤100 µg/mL OTC. When tetC was cloned and expressed alone in a sensitive strain, the transconjugants showed resistance to ≤250 µg/mL OTC. TetC and tetR expression was inducible by OTC in all six wild-type strains resistant to ≤100 µg/mL OTC. However, in the R1 strain resistant to ≤250 µg/mL OTC, tetR was not expressed, possibly due to the presence of Tn3 in the tetR gene, and in this case tetC was constitutively expressed. These data suggest that tetC confers OTC resistance in Xap strains, and tetR regulates the level of OTC resistance conferred by tetC. To our knowledge, this is the first report of OTC resistance in plant pathogenic xanthomonads.

A Long-Amplicon Viability-qPCR Test for Quantifying Living Pathogens that Cause Bacterial Spot in Tomato Seed.

Bacterial spot is one of the most serious diseases of tomato. It is caused by four species of Xanthomonas: X. euvesicatoria, X. gardneri, X. perforans, and X. vesicatoria. Contaminated or infected seed can be a major source of inoculum for this disease. The use of certified pathogen-free seed is one of the primary management practices to reduce the inoculum load in commercial production. Current seed testing protocols rely mainly on plating the seed extract and conventional PCR; however, the plating method cannot detect viable but nonculturable cells, and the conventional PCR assay has limited capability to differentiate DNA extracted from viable or dead bacterial cells. To improve the sensitivity and specificity of the tomato seed testing method for bacterial spot pathogens, a long-amplicon quantitative PCR (qPCR) assay coupled with propidium monoazide (PMA-qPCR) was developed to quantify selectively the four pathogenic Xanthomonas species in tomato seed. The optimized PMA-qPCR procedure was evaluated on pure bacterial suspensions, bacteria-spiked seed extracts, and seed extracts of inoculated and naturally infected seed. A crude DNA extraction protocol also was developed, and PMA-qPCR with crude bacterial DNA extracts resulted in accurate quantification of 104 to 108 CFU/ml of viable bacteria when mixed with dead cells at concentrations as high as 107 CFU/ml in the seed extracts. With DNA purified from concentrated seed extracts, the PMA-qPCR assay was able to detect DNA of the target pathogens in seed samples spiked with ≥75 CFU/ml (about 0.5 CFU/seed) of the viable pathogens. Latent class analysis of the inoculated and naturally infected seed samples showed that the PMA-qPCR assay had greater sensitivity than plating the seed extracts on the semiselective modified Tween Medium B and CKTM media for all four target species. Being much faster and more sensitive than dilution plating, the PMA-qPCR assay has potential to be used as a standalone tool or in combination with the plating method to improve tomato seed testing and advance the production of clean seed.

Ecology and population dynamics of yeast starter cultures in cocoa beans fermentation.

This study aimed to investigate controlled fermentation of cocoa beans with selected yeasts as starter cultures via integrating microbiological, biochemical, and chromatographic analyses. The steps involved in the yeast starter culture test were of the following order: 1) counting, isolation, purification, and biochemical identification of yeasts, 2) selection of ethanol-producing yeasts, 3) selection of thermotolerant yeasts, and 4) evaluation of physicochemical parameters of the selected yeasts in controlled fermentation of cocoa (F1 - Saccharomyces ssp. and Hanseniaspora ssp. and F2 - spontaneous fermentation - control). A total of 32 yeasts were isolated from three sampling points (M1, M2, and M3), which comprised 50% Candida ssp., 9.4% Rhodotorula ssp., 18.8% Saccharomyces ssp., and 18.8% Hanseniaspora ssp. The yeasts identified as Saccharomyces ssp. (n = 6) were subjected to the ethanol production test. Saccharomyces spp. CLV09 showed the highest concentration of ethanol in the simulated cocoa medium (3.5% v/v). Hanseniaspora spp. CVL20 and CVL19 strains showed the highest thermotolerance at 42°C after 72 h of growth. The starter cultures with Saccharomyces ssp. and Hanseniaspora ssp. showed a similar growth rate of the mesophilic aerobic population in both F1 and F2. Fermentation of the starter culture showed a higher production of organic acids than spontaneous fermentation (F2). Thus, Saccharomyces ssp. and Hanseniaspora ssp. can be used as a starter culture in cocoa fermentation.

Effectiveness of methods for cleaning arch wire: an in vitro study

The aim of this study was to evaluate various methods of removing bacterial and fungus biofilm, to simulate orthodontic arch wires cleaning before reinsertion in the patients appliance. Rectangular Nickel Titanium (NiTi), Stainless Steel (SS) and Titanium Molybdenum (TMA) wires were divided into five groups, then contaminated with strains of Streptococcus mutans and Candida albicas. Four segments of each group served as control and were not contaminated. Six cleanings methods were used to remove the biofilm: cotton roll and a chemical agent (chlorhexidine, sodium hypochlorite, 70% alcohol), cotton roll and water, steel woll and immersion on enzymatic detergent. There was a control group not decontaminated Then wires were placed in broth separately, and after an incubation period the optical density (OD) was measured, observing whether there was microbial growth. A wire segment of each subgroup of SS 3M® was taken to the Scanning Electron Microscope (SEM) for visualization of the treatment response. The results were submitted to one-way ANOVA test and Tukey post-test. With the exception of 70% alcohol, the disinfection means behaved similarly regardless the type of wire. Two percent Chlorhexidine and 1% Sodium Hypochlorite totally removed the microorganisms while other agents left a high microbial concentration. Chemical cleaning is necessary to remove biofilm in orthodontic wires; 1% Sodium Hypochlorite and 2% Chlorhexidine are good disinfectants for this purpose.

Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens.

Due to the emergence of multidrug-resistant pathogens, it is necessary to develop options to fight infections caused by these agents. Lactoferrin (Lf) is a cationic nonheme multifunctional glycoprotein of the innate immune system of mammals that provides numerous benefits. Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects. Lactoferrin is present in colostrum and milk and is also produced by the secondary granules of polymorphonuclear leukocytes, which store this glycoprotein and release it at sites of infection. Lf is also present in many fluids and exocrine secretions, on the surfaces of the digestive, respiratory and reproductive systems that are commonly exposed to pathogens. Apo-Lf (an iron-free molecule) can be microbiostatic due to its ability to capture ferric iron, blocking the availability of host iron to pathogens. However, apo-Lf is mostly microbicidal via its interaction with the microbial surface, causing membrane damage and altering its permeability function. Lf can inhibit viral entry by binding to cell receptors or viral particles. Lf is also able to counter different important mechanisms evolved by microbial pathogens to infect and invade the host, such as adherence, colonization, invasion, production of biofilms and production of virulence factors such as proteases and toxins. Lf can also cause mitochondrial and caspase-dependent regulated cell death and apoptosis-like in pathogenic yeasts. All of these mechanisms are important targets for treatment with Lf. Holo-Lf (the iron-saturated molecule) can contain up to two ferric ions and can also be microbicidal against some pathogens. On the other hand, lactoferricins (Lfcins) are peptides derived from the N-terminus of Lf that are produced by proteolysis with pepsin under acidic conditions, and they cause similar effects on pathogens to those caused by the parental Lf. Synthetic analog peptides comprising the N-terminus Lf region similarly exhibit potent antimicrobial properties. Importantly, there are no reported pathogens that are resistant to Lf and Lfcins; in addition, Lf and Lfcins have shown a synergistic effect with antimicrobial and antiviral drugs. Due to the Lf properties being microbiostatic, microbicidal, anti-inflammatory and an immune modulator, it represents an excellent natural alternative either alone or as adjuvant in the combat to antibiotic multidrug-resistant bacteria and other pathogens. This review aimed to evaluate the data that appeared in the literature about the effects of Lf and its derived peptides on pathogenic bacteria, protozoa, fungi and viruses and how Lf and Lfcins inhibit the mechanisms developed by these pathogens to cause disease.

Calidad de vida relacionada con salud en personas mayores que participan activamente en agrupaciones sociales / Health-Related Quality of Life among elderly people who actively participate in social groups

OBJETIVOS: Analizar la asociación entre calidad de vida relacionada con la salud (CVRS) y variables sociodemográficas, enfermedades crónicas y síndromes geriátricos en una muestra de personas mayores chilenas. MATERIAL Y MÉTODOS: Estudio transversal de 310 personas mayores de 60 años. Se aplicó el SF-36 y se evaluó el diagnóstico de enfermedades crónicas y síndromes geriátricos. Se realizan análisis descriptivos para los diversos dominios de SF-36, y a través de modelos de regresión jerárquica se determinan las variables que se asocian a componente sumario físico, componente de sumario mental y la escala general de SF-36. RESULTADOS: Las variables predictivas son: sexo, artrosis, trastorno de desplazamiento, incontinencia urinaria y depresión. Específicamente, la depresión es la variable más significativa en los diversos modelos contrastados. CONCLUSIÓN: La participación social activa influye positivamente en la CVRS. Desde el ámbito de la atención primaria se debe seguir avanzando en protocolos de intervención en salud mental

OBJECTIVES: To analyze the association between health-related quality of life (HR-QoL) and sociodemographic variables, chronic diseases and geriatric syndromes in a sample of Chilean elderly people. MATERIAL AND METHODS: A cross-sectional study of 310 people over 60 years of age. The SF-36 was applied, the diagnosis of chronic diseases and geriatric syndromes was evaluated. Descriptive analyzes are carried out for the different domains of SF-36 and through hierarchical regression models the variables that are associated to physical summary component, mental summary component and the general scale of SF-36 are determined. RESULTS: The predictive variables are: sex, arthritis, displacement disorder, urinary incontinence and depression. Specifically, depression is the most significant variable in the different contrasted models. CONCLUSION: Active social participation positively influences HR-QoL. In the area of primary care, progress must continue in intervention protocols in mental health

Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects.

Aristolochia trilobata, popularly known as "mil-homens," is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1ß, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

Differential expression of MAGEA6 toggles autophagy to promote pancreatic cancer progression.

The melanoma-associated antigen family A (MAGEA) antigens are expressed in a wide variety of malignant tumors but not in adult somatic cells, rendering them attractive targets for cancer immunotherapy. Here we show that a number of cancer-associated MAGEA mutants that undergo proteasome-dependent degradation in vitro could negatively impact their utility as immunotherapeutic targets. Importantly, in pancreatic ductal adenocarcinoma cell models, MAGEA6 suppresses macroautophagy (autophagy). The inhibition of autophagy is released upon MAGEA6 degradation, which can be induced by nutrient deficiency or by acquisition of cancer-associated mutations. Using xenograft mouse models, we demonstrated that inhibition of autophagy is critical for tumor initiation whereas reinstitution of autophagy as a consequence of MAGEA6 degradation contributes to tumor progression. These findings could inform cancer immunotherapeutic strategies for targeting MAGEA antigens and provide mechanistic insight into the divergent roles of MAGEA6 during pancreatic cancer initiation and progression.

Inhibition of ß-amyloid Aggregation of Ugni molinae Extracts.

The ß-amyloid peptide (1-42) is a molecule capable of aggregating into neurotoxic structures that have been implicated as potential etiological factors of Alzheimer's Disease. The aim of this study was to evaluate the inhibition of ß-amyloid aggregation of ethyl acetate and ethanolic extracts obtained from Ugni molinae leaves on neurotoxic actions of ß-amyloid aggregates. Chemical analyses were carried out with the extracts in order to determine their phenolic profile and its quantification. Both extracts showed a tendency to reduce neuronal deaths caused by ß-amyloid. This tendency was inversely proportional to the evaluated concentrations. Moreover, the effect of EAE and ETE on ß-amyloid aggregation was studied by fluorimetric T Thioflavin assay and transmission electronic microscopy (TEM); the extracts showed a modulation in the aggregation process. Partly, it is believed that these effects can be attributed to the polyphenolic compounds present in the extracts.

Perceptions of and Barriers to Lung Cancer Screening Among Physicians in Puerto Rico: A Qualitative Study.

Low-dose computed tomography (LDCT), an accepted U.S. screening tool for early lung cancer detection, is not widely-used in Puerto Rico. We investigated knowledge and attitudes about LDCT in focus groups of primary care physicians (PCP) and individuals at high risk for lung cancer (HRI) in Puerto Rico. Transcribed/translated audio-recorded discussions were analyzed with the constant comparison method. Both groups had limited knowledge about LDCT and concerns regarding insurance coverage. Most HRIs had never had a provider recommend LDCT and believed that having symptoms was necessary to obtain LDCT screening. Perceived barriers included fears about results and the procedure; a perceived benefit was having early detection and possibly being cured. Few PCPs had ever recommended LDCT to a patient, with those who had basing their decision on symptoms/smoking history but having challenges with insurance. More education on LDCT is needed among HRIs, and U.S. Preventive Services Task Force guidelines should be widely distributed to encourage physician recommendations.

Manejo no farmacológico del dolor en la atención del parto: experiencia desde las prácticas formativas / Non-pharmacological pain management in childbirth care: an experience from educational internship / Manejo não farmacológico da dor no atendimento do parto: experiência baseada nas práticas formativas

Resumen Introducción Describir las percepciones del estudiante de enfermería de una universidad privada, sobre la experiencia en la aplicación de las medidas no farmacológicas para el manejo del dolor en la atención del parto en el componente teórico y práctico. Materiales y Métodos Investigación cualitativa, con técnica de grupo focal, se utilizó entrevista semiestructurada y se organizaron dos grupos focales en el que participación 16 estudiantes de los cursos de V a VIII semestre matriculados durante el primer periodo del 2018. Resultados De los participantes, el 62.5% fueron mujeres y el 37.5% fueron hombres, la edad promedio fue 24.4 años (6.6%). Del análisis de las narrativas del grupo focal emergieron 2 categorías y 10 subcategorías definitivas: dentro de las categorías se destaca que los participantes identifican medidas no farmacológicas que se presentan en el componente teórico, pero no todas se logran realizar en los escenarios de práctica formativa, también surge inquietudes respecto a los mínimos insumos requeridos para conformar un kit para la realización de las medidas no farmacológicas para el manejo del dolor. Discusión A partir de los artículos investigados y el análisis realizado varios autores definen diferentes medidas no farmacológicas que son aplicables a la materna siendo estas efectivas y las cuales los estudiantes de enfermería aplican en su mayoría teniendo como resultado aspectos positivos y a mejorar. Conclusiones En general todos los participantes reconocen la importancia del uso de las medidas no farmacológicas para el manejo del dolor en la gestante durante la atención del parto, e identifican que estas medidas disminuyen la intensidad del dolor, ayudan disminuir el tiempo del trabajo de parto, y facilita la comunicación entre el personal de enfermería y la gestante.

Abstract Introduction To describe the perceptions of private-university nursing students on the experience from the implementation of non-pharmacological methods to manage pain in childbirth care in the theoretical and practical components. Materials and Methods Qualitative research with focus group technique; a semi-structured interview was used, and two focus groups were created with 16 students from 5-to-7-semester courses enrolled during the first term of 2018. Results 62.5% of the participants were women and 37.5% were men; the average age was 24.4 (6.6%). 2 categories and 10 subcategories emerged upon analyzing the narratives of the focus group. It is worth mentioning about the categories that the participants identify non-pharmacological methods present in the theoretical component, but not all methods can be implemented in educational internship scenarios; concerns also arose about the minimum inputs required to develop a kit for the implementation of non-pharmacological methods to manage pain. Discussion Based on the researched articles and the analysis performed, several authors established different non-pharmacological methods that are effective and applicable to mothers; nursing students apply such methods and generally obtain positive outcomes and lessons for improvement. Conclusions In general, all participants recognize the importance of using non-pharmacological methods to manage pain in pregnant women during childbirth care, and they also identify that these methods reduce pain intensity, help reducing the length of labor, and facilitate communication between nursing staff and pregnant women.

Resumo Introdução Descrever as percepções do estudante de enfermagem de uma universidade privada, sobre a experiência na aplicação das medidas não farmacológicas para o manejo da dor no atendimento do parto no componente teórico e prático. Materiais e Métodos Pesquisa qualitativa, com técnica de grupo focal, foi utilizado o método de entrevista semiestructurada e organizaram-se dois grupos focais onde participaram 16 estudantes dos cursos de V a VIII semestre matriculados durante o primeiro período de 2018. Resultados Dos participantes, 62,5% foram mulheres e 37,5% foram homens, a idade média foi de 24,4 anos (6,6%). A partir da análise das narrativas do grupo focal surgiram duas categorias e 10 subcategorias definitivas: dentro das categorias destaca-se que os participantes identificam medidas não farmacológicas que se apresentam no componente teórico, mas não todas são realizáveis no âmbito da prática formativa, também surgem inquietudes a respeito dos insumos mínimos requeridos para conformar um kit para a aplicação das medidas não farmacológicas para o manejo da dor. Discussão Com base nos artigos pesquisados e conforme a análise realizada, vários autores definem diferentes medidas não farmacológicas que são aplicáveis à materna sendo elas medidas efetivas que os estudantes de enfermagem aplicam predominantemente produzindo como resultado aspectos positivos e de melhora. Conclusões Em geral, todos os participantes reconhecem a importância do uso das medidas não farmacológicas para o manejo da dor na gestante durante o atendimento do parto e identificam que estas medidas diminuem a intensidade da dor, ajudam a diminuir o tempo do trabalho de parto, e facilita a comunicação entre o pessoal de enfermagem e a gestante.

Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer.

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional "omic" data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era.

The Ethyl Acetate Extract of Leaves of Ugni molinae Turcz. Improves Neuropathological Hallmarks of Alzheimer's Disease in Female APPswe/PS1dE9 Mice Fed with a High Fat Diet.

The most common type of dementia is Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by impairment in cognitive performance in aged individuals. Currently, there is no effective pharmacological treatment that cures the disease due to the lack of knowledge on the actual mechanisms involved in its pathogenesis. In the last decades, the amyloidogenic hypothesis has been the most studied theory trying to explain the origin of AD, yet it does not address all the concerns relating to its development. In the present study, a possible new preclinical treatment of AD was evaluated using the ethyl acetate extract (EAE) of leaves of Ugni molinae Turcz. (synonym Myrtus ugni Molina Family Myrtacea). The effects were assessed on female transgenic mice from a preclinical model of familial AD (APPswe/PS1dE9) combined with a high fat diet. This preclinical model was selected due to the already available experimental and observational data proving the relationship between obesity, gender, metabolic stress, and cognitive dysfunction; related to characteristics of sporadic AD. According to chemical analyses, EAE would contain polyphenols such as tannins, flavonoid derivatives, and phenolic acids, as well as pentacyclic triterpenoids that exhibit neuroprotective, anti-inflammatory, and antioxidant effects. In addition, the treatment evidenced its capacity to prevent deterioration of memory capacity and reduction of progression speed of AD neuropathology.