Intranasally administered extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells quickly incorporate into neurons and microglia in 5xFAD mice.

Introduction: Extracellular vesicles (EVs) released by human-induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs) have robust antiinflammatory and neurogenic properties due to therapeutic miRNAs and proteins in their cargo. Hence, hiPSC-NSC-EVs are potentially an excellent biologic for treating neurodegenerative disorders, including Alzheimer's disease (AD). Methods: This study investigated whether intranasally (IN) administered hiPSC-NSC-EVs would quickly target various neural cell types in the forebrain, midbrain, and hindbrain regions of 3-month-old 5xFAD mice, a model of ß-amyloidosis and familial AD. We administered a single dose of 25 × 109 hiPSC-NSC-EVs labeled with PKH26, and different cohorts of naïve and 5xFAD mice receiving EVs were euthanized at 45 min or 6 h post-administration. Results: At 45 min post-administration, EVs were found in virtually all subregions of the forebrain, midbrain, and hindbrain of naïve and 5xFAD mice, with predominant targeting and internalization into neurons, interneurons, and microglia, including plaque-associated microglia in 5xFAD mice. EVs also came in contact with the plasma membranes of astrocytic processes and the soma of oligodendrocytes in white matter regions. Evaluation of CD63/CD81 expression with the neuronal marker confirmed that PKH26 + particles found within neurons were IN administered hiPSC-NSC-EVs. At 6 h post-administration, EVs persisted in all cell types in both groups, with the distribution mostly matching what was observed at 45 min post-administration. Area fraction (AF) analysis revealed that, in both naïve and 5xFAD mice, higher fractions of EVs incorporate into forebrain regions at both time points. However, at 45 min post-IN administration, AFs of EVs within cell layers in forebrain regions and within microglia in midbrain and hindbrain regions were lower in 5xFAD mice than naïve mice, implying that amyloidosis reduces EV penetrance. Discussion: Collectively, the results provide novel evidence that IN administration of therapeutic hiPSC-NSC-EVs is an efficient avenue for directing such EVs into neurons and glia in all brain regions in the early stage of amyloidosis. As pathological changes in AD are observed in multiple brain areas, the ability to deliver therapeutic EVs into various neural cells in virtually every brain region in the early stage of amyloidosis is attractive for promoting neuroprotective and antiinflammatory effects.

Significados de familia para familias contemporáneas

(analítico) Frente a la existencia de diferentes formas familiares y para comprender el significado que el ser humano desde su diversidad le da a la familia, se realizó un estudio narrativo con enfoque cualitativo, usando como técnica la entrevista semiestructurada. Participaron integrantes de tres formas familiares: homoparental, con hijos producto de inseminación y adoptiva. Emergieron cinco categorías: definición de familia, aceptación, crianza, actitudes del medio familiar y social. El análisis concluye que el ser humano, desde su diversidad, le da un significado a la familia a partir de sus vivencias, sin diferenciar género, roles o funciones; por tanto, exigen derechos igualitarios frente a la conformación y dinámica familiar de los diferentes modelos y formas familiares, evidenciado la necesidad de ampliar la mirada sobre los significados atribuidos a la familia.

(analytical) Given the existence of different types of families, and with the aim of understanding the meaning that human beings give to the diverse expressions of family that currently exist, a qualitative narrative study using semi-structured interviews was carried out. Members of 3 different types of families participated: homoparental, families with children who are the result of artificial insemination and families that adopted their children. Five categories emerged from the interviews: the meaning of family, acceptance, parenting, social life and attitudes to the family environment. The study finds that human give meaning to their families based on their experiences without differentiating gender, functions or roles. They demand equal rights for the conformation of the different family types and models, demonstrating the need to broaden perspectives on meanings attributed to family.

(analítico) Diante da existência existência de diferentes formas familiares e com o objetivo de compreender o significado que o ser humano dá à família a partir de sua diversidade, foi realizado um estudo narrativo com abordagem qualitativa, utilizando como técnica a entrevista semiestruturada. Participaram membros de 3 formas familiares: homoparental, com filhos produto de inseminação e adotiva. Emergiram cinco categorias: definição de família, aceitação, criação, atitudes da família e ambiente social. Concluise que, a partir de sua diversidade, o ser humano dá sentido à família a partir de suas vivências, sem diferenciar gênero, papéis ou funções, portanto, demandam direitos iguais frente à conformação e dinâmica familiar dos diferentes modelos e formas de família, destacando a necessidade de ampliar o olhar sobre os significados atribuídos à familia.

Intranasally administered human MSC-derived extracellular vesicles inhibit NLRP3-p38/MAPK signaling after TBI and prevent chronic brain dysfunction.

Traumatic brain injury (TBI) leads to lasting brain dysfunction with chronic neuroinflammation typified by nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome activation in microglia. This study probed whether a single intranasal (IN) administration of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) naturally enriched with activated microglia-modulating miRNAs can avert chronic adverse outcomes of TBI. Small RNA sequencing confirmed the enrichment of miRNAs capable of modulating activated microglia in hMSC-EV cargo. IN administration of hMSC-EVs into adult mice ninety minutes after the induction of a unilateral controlled cortical impact injury resulted in their incorporation into neurons and microglia in both injured and contralateral hemispheres. A single higher dose hMSC-EV treatment also inhibited NLRP3 inflammasome activation after TBI, evidenced by reduced NLRP3, apoptosis-associated speck-like protein containing a CARD, activated caspase-1, interleukin-1 beta, and IL-18 levels in the injured brain. Such inhibition in the acute phase of TBI endured in the chronic phase, which could also be gleaned from diminished NLRP3 inflammasome activation in microglia of TBI mice receiving hMSC-EVs. Proteomic analysis and validation revealed that higher dose hMSC-EV treatment thwarted the chronic activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway by IL-18, which decreased the release of proinflammatory cytokines. Inhibition of the chronic activation of NLRP3-p38/MAPK signaling after TBI also prevented long-term cognitive and mood impairments. Notably, the animals receiving higher doses of hMSC-EVs after TBI displayed better cognitive and mood function in all behavioral tests than animals receiving the vehicle after TBI. A lower dose of hMSC-EV treatment also partially improved cognitive and mood function. Thus, an optimal IN dose of hMSC-EVs naturally enriched with activated microglia-modulating miRNAs can inhibit the chronic activation of NLRP3-p38/MAPK signaling after TBI and prevent lasting brain dysfunction.

Transcriptional Correlates of Chronic Alcohol Neuroadaptation in Drosophila Larvae.

When presented with the choice, Drosophila melanogaster females will often prefer to lay eggs on food containing a significant amount of alcohol. While, in some cases, this behavioral decision can provide a survival advantage to the developing larvae, it can also lead to developmental and cognitive problems. Alcohol consumption can affect executive functions, episodic memory, and other brain function capacities. However, in the fruit fly, the initial cognitive effects of alcohol consumption have been shown to reverse upon persistent exposure to alcohol. Using an olfactory conditioning assay where an odorant is implemented as a conditioned stimulus and paired with a heat shock as an unconditioned stimulus, a previous study has shown that when exposed to a short acute dose of alcohol, Drosophila larvae can no longer learn this association. Interestingly, upon prolonged chronic alcohol exposure, larvae seem to successfully avoid the conditioned stimulus just as well as control alcohol-naive larvae, suggestive of alcohol-induced neuroadaptations. However, the mechanisms by which Drosophila adapt to the presence of alcohol remains unknown. In this study, we explore the transcriptional correlates of neuroadaptation in Drosophila larvae exposed to chronic alcohol to understand the genetic and cellular components responsible for this adaptation. For this, we employed RNA sequencing technology to evaluate differences in gene expression in the brain of larvae chronically exposed to alcohol. Our results suggest that alcohol-induced neuroadaptations are modulated by a diverse array of synaptic genes within the larval brain through a series of epigenetic modulators.

Moderate, intermittent voluntary exercise in a model of Gulf War Illness improves cognitive and mood function with alleviation of activated microglia and astrocytes, and enhanced neurogenesis in the hippocampus.

Persistent cognitive and mood impairments in Gulf War Illness (GWI) are associated with chronic neuroinflammation, typified by hypertrophied astrocytes, activated microglia, and increased proinflammatory mediators in the brain. Using a rat model, we investigated whether a simple lifestyle change such as moderate voluntary physical exercise would improve cognitive and mood function in GWI. Because veterans with GWI exhibit fatigue and post-exertional malaise, we employed an intermittent voluntary running exercise (RE) regimen, which prevented exercise-induced stress. The GWI rats were provided access to running wheels three days per week for 13 weeks, commencing ten weeks after the exposure to GWI-related chemicals and stress (GWI-RE group). Groups of age-matched sedentary GWI rats (GWI-SED group) and naïve rats were maintained parallelly. Interrogation of rats with behavioral tests after the 13-week RE regimen revealed improved hippocampus-dependent object location memory and pattern separation function and reduced anxiety-like behavior in the GWI-RE group compared to the GWI-SED group. Moreover, 13 weeks of RE in GWI rats significantly reversed activated microglia with short and less ramified processes into non-inflammatory/antiinflammatory microglia with highly ramified processes and reduced the hypertrophy of astrocytes. Moreover, the production of new neurons in the hippocampus was enhanced when examined eight weeks after the commencement of RE. Notably, increased neurogenesis continued even after the cessation of RE. Collectively, the results suggest that even a moderate, intermittent physical exercise has the promise to improve brain function in veterans with GWI in association with suppression of neuroinflammation and enhancement of hippocampal neurogenesis.

Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus.

Metformin, a drug widely used for treating diabetes, can prolong the lifespan in several species. Metformin also has the promise to slow down age-related cognitive impairment. However, metformin's therapeutic use as an anti-aging drug is yet to be accepted because of conflicting animal and human studies results. We examined the effects of metformin treatment in late middle age on cognitive function in old age. Eighteen-month-old male C57BL6/J mice received metformin or no treatment for 10 weeks. A series of behavioral tests revealed improved cognitive function in animals that received metformin. Such findings were evident from a better ability for pattern separation, object location, and recognition memory function. Quantification of microglia revealed that metformin treatment reduced the incidence of pathological microglial clusters with alternative activation of microglia into an M2 phenotype, displaying highly ramified processes in the hippocampus. Metformin treatment also seemed to reduce astrocyte hypertrophy. Additional analysis demonstrated that metformin treatment in late middle age increased adenosine monophosphate-activated protein kinase activation, reduced proinflammatory cytokine levels, and the mammalian target of rapamycin signaling, and enhanced autophagy in the hippocampus. However, metformin treatment did not alter neurogenesis or synapses in the hippocampus, implying that improved cognitive function with metformin did not involve enhanced neurogenesis or neosynaptogenesis. The results provide new evidence that metformin treatment commencing in late middle age has promise for improving cognitive function in old age. Modulation of microglia, proinflammatory cytokines, and autophagy appear to be the mechanisms by which metformin facilitated functional benefits in the aged brain.

Representaciones sociales del consumo de bebidas energéticas en estudiantes de enfermería / Social representations of the energy drinks´ consumption in nursing students

Introducción: Las bebidas energéticas o energy drinks son sustancias con alto contenido de cafeína, su efecto estimulante las hace muy populares, sobre todo entre los jóvenes y universitarios, porque les prometen mejorar el rendimiento físico y cognitivo. Sin embargo, el incremento de su consumo puede generar dependencia, efectos tóxicos y letales. Objetivo: Describir las representaciones sociales del consumo de bebidas energéticas en estudiantes del primer semestre de Enfermería de la Fundación Universitaria del Área Andina. Métodos: Investigación de tipo cualitativo, a la luz de las representaciones sociales, con el empleo del método interrogativo. Se desarrolló en tres fases en las que se involucró a la población estudiada y se aplicó la técnica del grupo focal. Se tuvieron en cuenta las consideraciones éticas. Resultados: El núcleo central de la representación social del consumo de bebidas energéticas estuvo asociado a los efectos estimulantes que se generan a nivel del sistema nervioso central: inhibe el cansancio y el sueño y recupera energía. Sin embargo, los estudiantes participantes reconocieron que el abuso en su consumo es peligroso y puede ser letal, sobre todo si se mezcla con alcohol. Conclusiones: Las representaciones sociales del consumo de bebidas energéticas en estudiantes de primer semestre de Enfermería de la Fundación Universitaria del Área Andina, del curso 2017, se relacionan con conocimientos generales, con sus efectos y las motivaciones que tienen los estudiantes para consumirlas, porque les permite vivir la intensa vida universitaria y rendir en todos los contextos, social y laboral, de manera exitosa, aun conociendo sus consecuencias indeseables(AU)

Introduction: Energy drinks are substances with high caffeine content; its stimulating effect makes them very popular, especially among young people and university students, because they promise to improve physical performance and cognitive development. However, the increase in their consumption may generate dependency, toxic and deadly effects. Objective: To describe the social representations of the consumption of energy drinks in students of the first semester of Nursing at the University Foundation of the Andean Area. Methods: Qualitative research, in the light of the social representations, using the questioning method. It was developed in three phases involving the population studied and it was applied the focal group´s technique. There were taken into account the ethical considerations. Results: The core of social representation of energy drinks consumption was associated with the stimulant effects that are generated at the level of the central nervous system: they inhibit the tiredness and sleep and recovers energy. However, the students participating admitted that the abuse in energy drinks´ consumption is dangerous and can be lethal, especially if mixed with alcohol. Conclusions: The social representations of energy drinks´ consumption in first semester students of nursing at the University Foundation of the Andean Area, of the course 2017, are related with general knowledge, with their effects and the motivations that students have to consume them, because they allow them to live the intense university life and to have a good performance in all contexts (social and work ones) successfully, even knowing their undesirable consequences(AU)

Colonization history and population differentiation of the Honey Bees (Apis mellifera L.) in Puerto Rico.

Honey bees (Apis mellifera L.) are the primary commercial pollinators across the world. The subspecies A. m. scutellata originated in Africa and was introduced to the Americas in 1956. For the last 60 years, it hybridized successfully with European subspecies, previous residents in the area. The result of this hybridization was called Africanized honey bee (AHB). AHB has spread since then, arriving to Puerto Rico (PR) in 1994. The honey bee population on the island acquired a mosaic of features from AHB or the European honey bee (EHB). AHB in Puerto Rico shows a major distinctive characteristic, docile behavior, and is called gentle Africanized honey bees (gAHB). We used 917 SNPs to examine the population structure, genetic differentiation, origin, and history of range expansion and colonization of gAHB in PR. We compared gAHB to populations that span the current distribution of A. mellifera worldwide. The gAHB population is shown to be a single population that differs genetically from the examined populations of AHB. Texas and PR groups are the closest genetically. Our results support the hypothesis that the Texas AHB population is the source of gAHB in Puerto Rico.

A soft selective sweep during rapid evolution of gentle behaviour in an Africanized honeybee.

Highly aggressive Africanized honeybees (AHB) invaded Puerto Rico (PR) in 1994, displacing gentle European honeybees (EHB) in many locations. Gentle AHB (gAHB), unknown anywhere else in the world, subsequently evolved on the island within a few generations. Here we sequence whole genomes from gAHB and EHB populations, as well as a North American AHB population, a likely source of the founder AHB on PR. We show that gAHB retains high levels of genetic diversity after evolution of gentle behaviour, despite selection on standing variation. We observe multiple genomic loci with significant signatures of selection. Rapid evolution during colonization of novel habitats can generate major changes to characteristics such as morphological or colouration traits, usually controlled by one or more major genetic loci. Here we describe a soft selective sweep, acting at multiple loci across the genome, that occurred during, and may have mediated, the rapid evolution of a behavioural trait.

Sun protection for preventing basal cell and squamous cell skin cancers.

BACKGROUND: 'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks. OBJECTIVES: To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population. SEARCH METHODS: We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for eligibility using Early Review Organizing Software (EROS). Similarly, two review authors independently used predesigned data collection forms to extract information from the original study reports about the participants, methods of randomisation, blinding, comparisons of interest, number of participants originally randomised by arm, follow-up losses, and outcomes, and they assessed the risk of bias. We resolved any disagreement by consulting a third author and contacted trial investigators of identified trials to obtain additional information. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included one RCT (factorial design) that randomised 1621 participants.This study compared the daily application of sunscreen compared with discretionary use of sunscreen, with or without beta-carotene administration, in the general population. The study was undertaken in Australia; 55.2% of participants had fair skin, and they were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology. We found this study to be at low risk of bias for domains such as allocation, blinding, and incomplete outcome data. However, we found multiple unclear risks related to other biases, including an unclear assessment of possible interactions between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene). We found no difference in terms of the number of participants developing BCC (n = 1621; risk ratio (RR) 1.03, 95% confidence interval (CI) 0.74 to 1.43) or cSCC (n = 1621; RR 0.88, 95% CI 0.50 to 1.54) when comparing daily application of sunscreen with discretionary use, even when analyses were restricted to groups without beta-carotene supplementation. This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.We reported adverse events in a narrative way and included skin irritation or contact allergy.We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors. AUTHORS' CONCLUSIONS: In this review, we assessed the effect of solar protection in preventing the occurrence of new cases of keratinocyte cancer. We only found one study that was suitable for inclusion. This was a study of sunscreens, so we were unable to assess any other forms of sun protection. The study addressed our prespecified primary outcomes, but not most of our secondary outcomes. We were unable to demonstrate from the available evidence whether sunscreen was effective for the prevention of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC).Our certainty in the evidence was low because there was a lack of histopathological confirmation of BCC or cSCC in a significant percentage of cases. Amongst other sources of bias, it was not clear whether the study authors had assessed any interaction effects between the sunscreen and beta-carotene interventions. We think that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Capacidad buffer de la saliva en presencia de bebidas energéticas comercializadas en Chile, estudio in vitro / In vitro study of the buffering capacity of saliva in the presence of energy drinks sold in Chile

OBJETIVO Determinar la capacidad buffer de la saliva al ser añadida a distintas bebidas energéticas comercializadas en Chile, mediante mediciones de pH in vitro. MÉTODOS Fue requerida la participación de 3 pacientes jóvenes sistémicamente sanos, sin enfermedad de las glándulas salivales. Las muestras de saliva estimulada fueron obtenidas de cada paciente, las cuales fueron mezcladas y almacenadas en una sola muestra. Se seleccionaron 13 bebidas energéticas comercializadas a nivel nacional. Un total de 5 mL de cada bebida energética se distribuyó en 4 tubos Falcon. Se midió el pH de cada una de las bebidas energéticas, de la saliva y del agua potable. Se añadió 1 mL de agua potable al tubo Falcon número 1 y 1 mL de saliva a los 3 tubos restantes, cada 3 min hasta completar 13 mL de solución en cada uno (38% vol./vol.). Las mediciones de pH fueron realizadas en cada 1 mL añadido (saliva/agua), para permitir al ph-metro registrar de manera correcta. RESULTADOS Los rangos de pH para las bebidas energéticas van desde pH 2,42 ± 0,008 (Battery Gingered®), hasta pH 3,44 ± 0,005 (Battery Sugar Free®). La saliva en promedio tuvo un valor de pH 7,99 y el agua potable de 7,05. La bebida que más logró aumentar el pH, luego de agregar la saliva, fue la bebida Speed® que llegó a un valor de pH 4,38, mientras la que logró menos fue la bebida Quick Energy®, con un valor de pH 3,37. CONCLUSIÓN La capacidad buffer de la saliva logró aumentar entre 17 y 54% el pH de las bebidas energéticas analizadas en este estudio. Sin embargo, no pudo neutralizar los bajos niveles de pH de estas bebidas más allá de un pH final de 4,38, que es crítico para la estructura dentaria.

OBJECTIVE To determine, using in vitro pH measurements, the buffering capacity of saliva when added to different energy drinks sold in Chile. METHOD The participation of 3 young and systemically healthy patients, with no diseases of the saliva glands, was obtained. Samples of stimulated saliva where obtained from each patient and then mixed and stored as one sample. The study used 13 energy drinks sold nationwide, with 5 mL of each one being distributed into 4 Falcon tubes. The pH of each of the energy drinks, the saliva sample, and drinking water was measured. 1 mL of drinking water was added into Falcon tube number 1, and 1 mL of saliva into the 3 remaining every 3 min until completing 13 mL of solution in each one (38% vol./vol.). The pH measurements where performed upon adding each 1 mL (saliva/water) to allow the pH meter to correctly register the data. RESULTS The pH levels for energy drinks range between pH 2.42 ± 0.008 (Battery Gingered®), to pH 3.44 ± 0.005 (Battery Sugar Free®). The saliva had a mean pH value of 7.99, and 7.05 for drinkable water. The energy drink that achieved a higher increase in pH level was Speed®, reaching a value of pH 4.38, while the energy drink that increased the pH level the least was Quick Energy®, only reaching a pH of 3.37. CONCLUSION The buffering capacity of saliva managed to increase the pH level of energy drinks analyzed in this study between 17 and 54%. However, saliva was unable to neutralize further than 4.38 the low levels of pH in these drinks, thus being critical to dental structure.

Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico.

BACKGROUND: The Africanized honey bee is one of the most spectacular invasions in the Americas. African bees escaped from apiaries in Brazil in 1956, spread over Americas and by 1994 they were reported in Puerto Rico. In contrast to other places, the oceanic island conditions in Puerto Rico may mean a single introduction and different dynamics of the resident European and new-coming Africanized bees.To examine the genetic variation of honey bee feral populations and colonies from different locations in Puerto Rico, we used eight known polymorphic microsatellite loci. RESULTS: In Puerto Rico, gAHB population does not show any genetic structure (Fst = 0.0783), and is best described as one honey bee population, product of hybridization of AHB and EHB. The genetic variability in this Africanized population was similar to that reported in studies from Texas. We observed that European private allele frequencies are high in all but one locus. This contrasts with mainland Africanized populations, where European allele frequencies are diminished. Two loci with European private alleles, one on Linkage Group 7, known to carry two known defensiveness Quantitative Trait Loci (QTLs), and the other on Linkage Group 1, known to carry three functionally studied genes and 11 candidate genes associated with Varroa resistance mechanisms were respectively, significantly greater or lower in European allele frequency than the other loci with European private alleles. CONCLUSIONS: Genetic structure of Puerto Rico gAHB differs from mainland AHB populations, probably representing evolutionary processes on the island.

Adapting a program to inform African American and Hispanic American women about cancer clinical trials.

The dearth of evidence-based clinical trial education programs may contribute to the under-representation of African American and Hispanic American women in cancer research studies. This study used focus group-derived data from 80 women distributed among eight Spanish- and English-language focus groups. These data guided the researchers' adaptation and refinement of the National Cancer Institute's various clinical trials education programs into a program that was specifically focused on meeting the information needs of minority women and addressing the barriers to study participation that they perceived. A "sisterhood" theme was adopted and woven throughout the presentation.

Mujeres en tratamiento de cáncer, acogidas por un albergue de apoyo: circunstancias y perspectivas de cuidado de enfermería / Women receiving cancer treatment supported by a housing support: circumstances and perspectives in nursing care

Se realizó un estudio de tipo cualitativo basado en 13 entrevistas a profundidad a mujeres con cáncer entre los 33 y los 70 años, con diferentes diagnósticos, provenientes de varias regiones de Colombia, vinculadas al régimen subsidiado, y que son acogidas por un albergue durante su estadía en Bogotá con motivo de su tratamiento en el Instituto Nacional de Cancerología (INC) con el fin de conocer sus circunstancias y sus necesidades de cuidado de enfermería. De las mujeres, 8 tienen un cáncer de tipo ginecológico y de este grupo 5 viven con cáncer de mama. En 4 de los 13 casos el diagnóstico fue tardío. Para todas las mujeres ha sido difícil asimilar su diagnóstico, asociándolo a la posibilidad de morir; luego ha sobrevenido una etapa de aceptación de su realidad de salud y de afrontamiento. Para este grupo, el INC y el Albergue constituyen redes sociales significativas; la lejanía de sus allegados es una dificultad que destacan del hecho de tener que desplazarse a la capital. La mayoría de las participantes buscan sentirse activas; los aspectos psicosociales son prioritarios entre sus necesidades; desean profundizar en su conocimiento de la enfermedad; es importante para ellas desarrollar mayores habilidades de auto cuidado para minimizar efectos adversos y síntomas. Fortalecer las redes de acompañamiento e interacción generadas entre ellas así como apoyarlas para fortalecer sus perspectivas de afrontamiento de su enfermedad y de autocuidado hacen parte de las estrategias que se proponen para otorgar mayor sentido a la cotidianidad y para favorecer su salud mental y su calidad de vida durante el tiempo que duran sus tratamientos en la capital.

Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model.

This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop murine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P < 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P < 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 +/- 8.9 ng/mL versus 3.2 +/- 0.8 ng/mL, P < 0.05) relative to the HF group. Akt (Ser(473)) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells.

Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro.

The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.

Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2.

PURPOSE: To determine whether altering the dietary content of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels. EXPERIMENTAL DESIGN: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. RESULTS: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression. CONCLUSION: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.

Localization of Müllerian mimicry genes on a dense linkage map of Heliconius erato.

We report a dense genetic linkage map of Heliconius erato, a neotropical butterfly that has undergone a remarkable adaptive radiation in warningly colored mimetic wing patterns. Our study exploited natural variation segregating in a cross between H. erato etylus and H. himera to localize wing color pattern loci on a dense linkage map containing amplified fragment length polymorphisms (AFLP), microsatellites, and single-copy nuclear loci. We unambiguously identified all 20 autosomal linkage groups and the sex chromosome (Z). The map spanned a total of 1430 Haldane cM and linkage groups varied in size from 26.3 to 97.8 cM. The average distance between markers was 5.1 cM. Within this framework, we localized two major color pattern loci to narrow regions of the genome. The first gene, D, responsible for red/orange elements, had a most likely placement in a 6.7-cM region flanked by two AFLP markers on the end of a large 87.5-cM linkage group. The second locus, Sd, affects the melanic pattern on the forewing and was found within a 6.3-cM interval between flanking AFLP loci. This study complements recent linkage analysis of H. erato's comimic, H. melpomene, and forms the basis for marker-assisted physical mapping and for studies into the comparative genetic architecture of wing-pattern mimicry in Heliconius.