Reciprocal Changes in miRNA Expression with Pigmentation and Decreased Proliferation Induced in Mouse B16F1 Melanoma Cells by L-Tyrosine and 5-Bromo-2'-Deoxyuridine.

Background: Many microRNAs have been identified as critical mediators in the progression of melanoma through its regulation of genes involved in different cellular processes such as melanogenesis, cell cycle control, and senescence. However, microRNAs' concurrent participation in syngeneic mouse B16F1 melanoma cells simultaneously induced decreased proliferation and differential pigmentation by exposure to 5-Brd-2'-dU (5'Bromo-2-deoxyuridine) and L-Tyr (L-Tyrosine) respectively, is poorly understood. Aim: To evaluate changes in the expression of microRNAs and identify which miRNAs in-network may contribute to the functional bases of phenotypes of differential pigmentation and reduction of proliferation in B16F1 melanoma cells exposed to 5-Brd-2'-dU and L-Tyr. Methods: Small RNAseq evaluation of the expression profiles of miRNAs in B16F1 melanoma cells exposed to 5-Brd-2'-dU (2.5 µg/mL) and L-Tyr (5 mM), as well as the expression by qRT-PCR of some molecular targets related to melanogenesis, cell cycle, and senescence. By bioinformatic analysis, we constructed network models of regulation and co-expression of microRNAs. Results: We confirmed that stimulation or repression of melanogenesis with L-Tyr or 5-Brd-2'-dU, respectively, generated changes in melanin concentration, reduction in proliferation, and changes in expression of microRNAs 470-3p, 470-5p, 30d-5p, 129-5p, 148b-3p, 27b-3p, and 211-5p, which presented patterns of coordinated and reciprocal co-expression, related to changes in melanogenesis through their putative targets Mitf, Tyr and Tyrp1, and control of cell cycle and senescence: Cyclin D1, Cdk2, Cdk4, p21, and p27. Conclusions: These findings provide insights into the molecular biology of melanoma of the way miRNAs are coordinated and reciprocal expression that may operate in a network as molecular bases for understanding changes in pigmentation and decreased proliferation induced in B16F1 melanoma cells exposed to L-Tyr and 5-Brd-2'-dU.

Systematic review indicates postnatal growth in term infants born small-for-gestational-age being associated with later neurocognitive and metabolic outcomes.

We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affect neurodevelopment and metabolic outcomes in term-born small-for-gestational-age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass and blood pressure (BP), but had no effect on early neurocognitive outcomes. Meanwhile, 31 observational studies reported consistent positive associations between postnatal weight gain and growth with neurocognitive outcomes, adiposity, insulin resistance and BP. CONCLUSION: Few intervention studies exist, despite consistent positive associations between early growth and neurocognition in term-born SGA infants.

Lack of Measles Transmission to Susceptible Contacts from a Health Care Worker with Probable Secondary Vaccine Failure - Maricopa County, Arizona, 2015.

On January 23, 2015, the Maricopa County Department of Public Health (MCDPH) was notified of a suspected measles case in a nurse, a woman aged 48 years. On January 11, the nurse had contact with a patient with laboratory-confirmed measles associated with the Disneyland theme park-related outbreak in California. On January 21, she developed a fever (103°F [39.4°C]), on January 23 she experienced cough and coryza, and on January 24, she developed a rash. The patient was instructed to isolate herself at home. On January 26, serum, a nasopharyngeal swab, and a urine specimen were collected. The following day, measles infection was diagnosed by real time reverse transcription polymerase chain reaction testing of the nasopharyngeal swab and urine specimen and by detection of measles-specific immunoglobulin (Ig)M and IgG in serum by enzyme-linked immunosorbent assay. Because of her symptoms and laboratory results, the patient was considered to be infectious.

Optimal Protein Intake in Healthy Children and Adolescents: Evaluating Current Evidence.

High protein intake might elicit beneficial or detrimental effects, depending on life stages and populations. While high protein intake in elder individuals can promote beneficial health effects, elevated protein intakes in infancy are discouraged, since they have been associated with obesity risks later in life. However, in children and adolescents (4-18 years), there is a scarcity of data assessing the effects of high protein intake later in life, despite protein intake being usually two- to three-fold higher than the recommendations in developed countries. This narrative review aimed to revise the available evidence on the long-term effects of protein intake in children and adolescents aged 4-18 years. Additionally, it discusses emerging techniques to assess protein metabolism in children, which suggest a need to reevaluate current recommendations. While the optimal range is yet to be firmly established, available evidence suggests a link between high protein intake and increased Body Mass Index (BMI), which might be driven by an increase in Fat-Free Mass Index (FFMI), as opposed to Fat Mass Index (FMI).

Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor.

Metacaspases are caspase family cysteine peptidases found in plants, fungi, and protozoa but not mammals. Trypanosoma brucei is unusual in having five metacaspases (MCA1-MCA5), of which MCA1 and MCA4 have active site substitutions, making them possible non-enzymatic homologues. Here we demonstrate that recombinant MCA4 lacks detectable peptidase activity despite maintaining a functional peptidase structure. MCA4 is expressed primarily in the bloodstream form of the parasite and associates with the flagellar membrane via dual myristoylation/palmitoylation. Loss of function phenotyping revealed critical roles for MCA4; rapid depletion by RNAi caused lethal disruption to the parasite's cell cycle, yet the generation of MCA4 null mutant parasites (Δmca4) was possible. Δmca4 had normal growth in axenic culture but markedly reduced virulence in mice. Further analysis revealed that MCA4 is released from the parasite and is specifically processed by MCA3, the only metacaspase that is both palmitoylated and enzymatically active. Accordingly, we have identified that the multiple metacaspases in T. brucei form a membrane-associated proteolytic cascade to generate a pseudopeptidase virulence factor.

Changes in cytoarchitecture and mobility in B16F1 melanoma cells induced by 5-Br-2'-dU coincide with Rock2, miRNAs 138-5p and 455-3p reciprocal expressions.

ROCK2 is a protein involved in the restructuring of the cytoskeleton in cell adhesion and contractibility processes. miR-138-5p and miR-455-3p regulate Rock2 expression, cell proliferation, migration, and invasion in different experimental cell models. However, their participation in the cytoarchitecture and mobility of B16F1 melanoma cells exposed to 5-Br-2'-dU is partially known. This work aimed to analyze ROCK2 and miRs 138-5p and 455-3p expression associated with morphological and mobility changes of B16F1 mouse melanoma cells exposed to the thymidine analog 5-Bromo-2'-deoxyuridine (5-Br-2'-dU). We observed an increase (2.2X n = 3, p < 0.05) in the cell area, coinciding with an increase in cell diameter (1.27X n = 3, p < 0.05), as well as greater cell granularity, capacity for circularization, adhesion, which was associated with more significant polymerization of F-actin, collapsed in the intermediate filaments of vimentin (VIM), and coinciding with a decrease in migration (87%). Changes coincided with a decrease in Rock2 mRNA expression (2.88X n = 3, p < 0.05), increased vimentin and a reciprocal decrease in miR-138-5p (1.8X), and an increase in miR-455-3p (2.39X). The Rock2 kinase inhibitor Y27632 partially rescued these changes. These results suggest ROCK2 and VIM regulate the morphological and mobility changes of B16 melanoma cells after exposure to 5-Br-2'-dU, and its expression may be reciprocally regulated, at least in part, by miR-138-5p and miR-455-3p.

Physiological Impact of Palm Olein or Palm Oil in Infant Formulas: A Review of Clinical Evidence.

Palm oil/olein (PO/POL) is used in infant formulas to imitate the fatty acid profile of human milk (HM) and achieve similar levels of palmitic acid (PA). However, the positions of fatty acids on the triacylglyceride differ between PO/POL and HM, which affect fat absorption and produce unintended physiological consequences. Recent papers have reviewed evidence for physiological benefits of PO/POL and beta-palmitate (sn-2-palmitate) in infant formulas. The aim of the present review is to supplement the assessment of available clinical evidence on the physiological effects of PO/POL formulas in healthy infants. We intend to focus on PO/POL and not on sn-2-palmitate, since the latter was recently extensively reviewed. Clinical evidence supports that PO/POL in infant formulas leads to a lower fat, DHA, palmitate and calcium absorption, and bone mineralization; soft stools; and growth (weight accretion) compared to formulas without PO/POL. Consequently, it seems prudent to be considerate and cautious when adding PO/POL to infant formulas. While HM is the gold standard for infant nutrition, the development of infant formula should be based on achieving positive physiological outcomes, rather than just replicating HM nutrient composition.

Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement.

Leishmaniasis treatment is hampered by the increased appearance of treatment failure. ATP-binding cassette (ABC) transporters are usually involved in drug resistance both in tumor cells and in microorganisms. Here we report the characterization of an ABCG-like transporter, LiABCG6, localized mainly at the plasma membrane in Leishmania protozoan parasites. When overexpressed, this half-transporter confers significant resistance to the leishmanicidal agents miltefosine and sitamaquine. This resistance phenotype is mediated by a reduction in intracellular drug accumulation. LiABCG6 also reduces the accumulation of short-chain fluorescent phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. As a whole, these results suggest that LiABCG6 could be implicated in phospholipid trafficking and drug resistance.

Building a Beneficial Microbiome from Birth.

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota.

2'-fucosyllactose: an abundant, genetically determined soluble glycan present in human milk.

Lactose is the preeminent soluble glycan in milk and a significant source of energy for most newborn mammals. Elongation of lactose with additional monosaccharides gives rise to a varied repertoire of free soluble glycans such as 2'-fucosyllactose (2'-FL), which is the most abundant oligosaccharide in human milk. In infants, 2'-FL is resistant to digestion and reaches the colon where it is partially fermented, behaving as soluble prebiotic fiber. Evidence also suggests that portions of small soluble milk glycans, including 2'-FL, are absorbed, thus raising the possibility of systemic biological effects. 2'-FL bears an epitope of the Secretor histo-blood group system; approximately 70-80% of all milk samples contain 2'-FL, since its synthesis depends on a fucosyltransferase that is not uniformly expressed. The fact that some infants are not exposed to 2'-FL has helped researchers to retrospectively probe for biological activities of this glycan. This review summarizes the attributes of 2'-FL in terms of its occurrence in mammalian phylogeny, its postulated biological activities, and its variability in human milk.

Estrés en estudiantes de enfermería / Stress in Nursing students

Introducción: los profesionales de la salud están expuestos a situaciones estresantes, las cuales generan importantes consecuencias negativas para la salud; incluso durante el periodo de formación. El adecuado afrontamiento de las situaciones que generan estrés durante las prácticas puede dificultar el aprendizaje y el futuro desarrollo profesional.Objetivos: evaluar el nivel de estrés en estudiantes de enfermería durante el período de formación práctica, su significación y su posible relación con el año académico cursado. Métodos: los instrumentos de medida utilizados fueron la escala de estrés percibido (PSS-14) y el cuestionario KEZKAK que mide los estresores en las prácticas clínicas. De los 744 estudiantes matriculados, se recogió una muestra compuesta por 289 estudiantes (39 porciento) pertenecientes al área de enfermería de la Universidad Alfonso X el Sabio (Madrid-España) en el periodo de los 3 cursos de formación de dicha disciplina. La media de edad de los alumnos evaluados fue de 21 años. Resultados: a lo largo de todos los cursos las mujeres sufren más estrés que los hombres. El segundo curso en el que se produce una mayor percepción de estrés. En cuanto a las situaciones que producen mayor nivel de estrés, se describen algunos componentes significativos: "Estrés por competencia profesional"," Estrés por interacción con el paciente"," Estrés por confrontación con el sufrimiento" y" Estrés por relación profesional". Conclusión: el nivel de estrés se relaciona con el año académico cursado(AU)

Introduction: Health professionals are exposed to stressful situations, which produce important negative consequences for their health, even during the training period. The appropriate way they cope with the situations that produce stress during the practices can make learning and future professional development difficult. Objective: To evaluate the level of stress in Nursing students during the period of their practical training, its significance and its possible relation with the academic year in course. Methods: The measurement instruments used were the perceived stress scale (PSS-14) and the KEZKAK questionnaire that measures stressors in clinical practice. Out of the 744 students enrolled, a sample of 289 students (39 percent) belonging to the Nursing area of ​​the Alfonso X el Sabio University (Madrid-Spain) was chosen during the three training courses of this discipline. The mean age of the students evaluated was 21 years. Results: Throughout the academic years, women suffer more stress than men. The second year is the one in which there is a greater perception of stress. As for the situations that produce a greater level of stress, some significant components are described: stress by professional competence, stress by interaction with the patient, stress by confrontation with suffering, and stress by professional relation. Conclusion: the level of stress is related to the academic year in course(AU)

Prevention of central venous catheter-associated bloodstream infections in pediatric intensive care units: a performance improvement collaborative.

OBJECTIVE: The goal of this effort was to reduce central venous catheter (CVC)-associated bloodstream infections (BSIs) in pediatric intensive care unit (ICU) patients by means of a multicenter evidence-based intervention. METHODS: An observational study was conducted in 26 freestanding children's hospitals with pediatric or cardiac ICUs that joined a Child Health Corporation of America collaborative. CVC-associated BSI protocols were implemented using a collaborative process that included catheter insertion and maintenance bundles, daily review of CVC necessity, and daily goals. The primary goal was either a 50% reduction in the CVC-associated BSI rate or a rate of 1.5 CVC-associated BSIs per 1,000 CVC-days in each ICU at the end of a 9-month improvement period. A 12-month sustain period followed the initial improvement period, with the primary goal of maintaining the improvements achieved. RESULTS: The collaborative median CVC-associated BSI rate decreased from 6.3 CVC-associated BSIs per 1,000 CVC-days at the start of the collaborative to 4.3 CVC-associated BSIs per 1,000 CVC-days at the end of the collaborative. Sixty-five percent of all participants documented a decrease in their CVC-associated BSI rate. Sixty-nine CVC-associated BSIs were prevented across all teams, with an estimated cost avoidance of $2.9 million. Hospitals were able to sustain their improvements during a 12-month sustain period and prevent another 198 infections. CONCLUSIONS: We conclude that our collaborative quality improvement project demonstrated that significant reduction in CVC-associated BSI rates and related costs can be realized by means of evidence-based prevention interventions, enhanced communication among caregivers, standardization of CVC insertion and maintenance processes, enhanced measurement, and empowerment of team members to enforce adherence to best practices.

A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids.

ATP-binding cassette (ABC) transporters represent an important family of membrane proteins involved in drug resistance and other biological activities. The present work reports the characterization of the first ABC subfamily G (ABCG)-like transporter, LiABCG4, in the protozoan parasite Leishmania. LiABCG4 localized mainly to the parasite plasma membrane. Overexpression of this half-transporter reduced the accumulation of phosphatidylcholine analogues and conferred resistance to alkyl-phospholipids. Likewise, when expressed in Saccharomyces cerevisiae, the protein localized to the yeast plasma membrane and conferred resistance to alkyl-phospholipids. Post-Golgi secretory vesicles isolated from a LiABCG4-overexpressing yeast mutant contained the leishmanial ABC transporter and exhibited ATP-dependent, vanadate-sensitive transport of phosphatidylcholine analogues from the cytosolic to the lumenal leaflet of the vesicle membrane. Cross-linking showed dimerization of LiABCG4. These results suggest that LiABCG4 is involved in the active transport of phosphatidylcholine and resistance to alkyl-phospholipids in Leishmania.

Estudio de la actividad quirúrgica: una herramientade registro de tiempos / Analysis of surgical activity: description and use of a tool for registering operating room time

Objetivo: Elaborar una herramienta para recoger y analizar los distintos tiempos quirúrgicos, para posteriormente introducir medidas correctoras que optimicen el rendimiento del bloque quirúrgico. Material y métodos: Estudio prospectivo durante 2000 y 2001. En una hoja de cálculo elaborada al efecto se registraron las siguientes variables de estudio: tiempo ofertado total, tiempo utilizado efectivo, tiempo no utilizado, tiempo de prolongación en cirugía programada, tiempo de limpieza, tiempo de preparación, tiempo de entrada y tiempo de cambio de quirófano. Resultados: Se analizaron los tiempos de un total de 8.266 intervenciones en 2000 y 8.895 en 2001. El tiempo de ocupación efectivo fue del 84,6 por ciento en 2000, y en 2001 pasó al 80,4 por ciento. El tiempo de cambio se redujo de 21 a 20 min (AU)

Lipoproteínas de baja y muy baja densidad glicosiladas en un grupo de pacientes diabéticos / Glycosylate low and very low lipoproteins in a group of diabetic patients

Se utilizó la reacción con ácido tiobarbitúrico para cuantificar el grado de gicosilación de las lipoproteínas de baja y muy baja densidad una vez precipitadas con ácido fosfotúngstico y cloruro de magnesio. Se midió la glicosilación de estas lipoproteínas en 50 pacientes diabéticos con diferente grado de compensación metabólica de acuerdo con los valores de hemoglobina glicosilada y en 31 controles no diabéticos con glicemia inferior a 5 mmol/L. Se encontraron diferencias significativas en los valores de lipoproteínas glicosiladas entre los controles y los pacientes diabéticos descompensados (p < 0,001) y dentro de estos últimos con diferentes grados de descompensación metabólica. Se encontró una correlación positiva (p < 0,005) entre los valores de glicemia y de hemoglobina glicosilada con las lipoproteínas glicosiladas

Lipoproteínas de baja y muy baja densidad glicosiladas en un grupo de pacientes diabéticos / Glycosylate low and very low lipoproteins in a group of diabetic patients

Se utilizó la reacción con ácido tiobarbitúrico para cuantificar el grado de gicosilación de las lipoproteínas de baja y muy baja densidad una vez precipitadas con ácido fosfotúngstico y cloruro de magnesio. Se midió la glicosilación de estas lipoproteínas en 50 pacientes diabéticos con diferente grado de compensación metabólica de acuerdo con los valores de hemoglobina glicosilada y en 31 controles no diabéticos con glicemia inferior a 5 mmol/L. Se encontraron diferencias significativas en los valores de lipoproteínas glicosiladas entre los controles y los pacientes diabéticos descompensados (p < 0,001) y dentro de estos últimos con diferentes grados de descompensación metabólica. Se encontró una correlación positiva (p < 0,005) entre los valores de glicemia y de hemoglobina glicosilada con las lipoproteínas glicosiladas

Cirugía ginecológica en la tercera edad / Gynecologic surgery in third age

Se revisaron 72 pacientes mayores de 65 años con cirugía ginecológica. La mayor parte de pacientes estaba entre 65 y 69 años. Había padecimientos cardiovasculares en 40.2%; la indicación de la cirugía fue distopias genitales en 80.5%. La histerectomía vaginal (41.6%) y plastía vaginal (39.9%) fueron procedimientos más frecuentes. La morbilidad fué de 10.4%. No hubo mortalidad. La edad más avanzada no contraindica la cirugía ginecológica

Centros comunales de rehidratación oral / Oral rehidratation communitary facilities

Demuestra los resultados de un método comunitario, destinado a incrementar el conocimiento y uso de las sales rehidratantes y constituye un ejemplo de cómo realizar una labor comunitaria manteniendo el método de la auto crítica científica