Lipophorin receptors regulate mushroom body development and complex behaviors in Drosophila.

BACKGROUND: Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain. RESULTS: We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the mushroom bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurite arborization. This effect depends on LpRs and Dab, the Drosophila ortholog of the Reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events. CONCLUSIONS: These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.

Lamp1 Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in Drosophila Models of Parkinson Disease.

Parkinson disease (PD) is a common neurodegenerative condition affecting people predominantly at old age that is characterized by a progressive loss of midbrain dopaminergic neurons and by the accumulation of α-synuclein-containing intraneuronal inclusions known as Lewy bodies. Defects in cellular degradation processes such as the autophagy-lysosomal pathway are suspected to be involved in PD progression. The mammalian Lysosomal-associated membrane proteins LAMP1 and LAMP2 are transmembrane glycoproteins localized in lysosomes and late endosomes that are involved in autophagosome/lysosome maturation and function. Here, we show that the lack of Drosophila Lamp1, the homolog of LAMP1 and LAMP2, severely increased fly susceptibility to paraquat, a pro-oxidant compound known as a potential PD inducer in humans. Moreover, the loss of Lamp1 also exacerbated the progressive locomotor defects induced by the expression of PD-associated mutant α-synuclein A30P (α-synA30P) in dopaminergic neurons. Remarkably, the ubiquitous re-expression of Lamp1 in a mutant context fully suppressed all these defects and conferred significant resistance towards both PD factors above that of wild-type flies. Immunostaining analysis showed that the brain levels of α-synA30P were unexpectedly decreased in young adult Lamp1-deficient flies expressing this protein in comparison to non-mutant controls. This suggests that Lamp1 could neutralize α-synuclein toxicity by promoting the formation of non-pathogenic aggregates in neurons. Overall, our findings reveal a novel role for Drosophila Lamp1 in protecting against oxidative stress and α-synuclein neurotoxicity in PD models, thus furthering our understanding of the function of its mammalian homologs.

Effectiveness of a motivational intervention on overweight/obese patients in the primary healthcare: a cluster randomized trial.

BACKGROUND: Overweight and obesity are common health problems which increase the risk of developing several serious health conditions. The main difficulty in the management of weight-loss lies in its maintenance, once it is achieved. The aim of this study was to investigate whether a motivational intervention, together with current clinical practice, was more efficient than a traditional intervention, in the treatment of overweight and obesity and whether this intervention reduces cardiovascular risk factors associated with overweight and obesity. METHODS: Multi-centre cluster randomized trial with a 24-month follow-up included 864 overweight/obese patients randomly assigned. Motivational intervention group (400 patients), delivered by a nurse trained by an expert psychologist, in 32 sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard programmed diet and exercise. The control group (446 patients), received the usual follow-up. RESULTS: Weight reduction was statistically significant in the second year with a mean reduction of 1.0 Kg in the control group and 2.5 Kg in the intervention group (p = 0. 02). While 18.1% of patients in the control group reduced their weight by more than 5%, this percentage rose to 26.9% in the intervention group, which is statistically significant (p = 0.04). Patients in the motivational intervention group had significantly greater improvements in triglycerides and APOB/APOA1ratio. CONCLUSIONS: The results highlight the importance of the group motivational interview in the treatment of overweight /obese patients in primary care, and in the improvement of their associated cardiovascular risks factors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01006213 October 30, 2009.

Supporting a double hospitalization during the pandemic: The experience of fathers whose infants were hospitalized while their mothers were also hospitalized due to COVID-19. / Acompañar una doble hospitalización en pandemia: la experiencia de padres con bebés hospitalizados mientras las madres se encuentran hospitalizadas por COVID-19.

Introduction. The hospitalization of a baby in the neonatal intensive care unit may be highly stressful for both mothers and fathers, and this was even more intense in the context of the COVID-19 pandemic. To date, no studies have been found that describe the experience of fathers who underwent the simultaneous hospitalization of their partner and newborn infant during the COVID-19 pandemic. Objectives. To explore the experience of fathers who had their babies hospitalized in the Neonatal Unit while their partner were hospitalized due to worsening of COVID-19. Population and method. Four semi-structured interviews were conducted and analyzed using an interpretative phenomenological analysis. Results. Four moments were identified when specific emotions arose: a) onset of infection, b) partner hospitalization, c) baby birth, and d) baby hospitalization. Guilt, fear, death anxiety, loneliness, and uncertainty appear very early and are later combined with emotions such as happiness and empowerment, among others. The lack of physical contact with their partners and babies and failures in communication with the health care team stand out as factors that hinder the exercise of the paternal role, while an effective communication with the health care team and active participation in the baby's care are protective factors. Fathers fulfill multiple roles, the most important of which is their role as protectors. Conclusions. Family-centered communication and care and active involvement in baby care may potentially protect against the impact of this complex experience of double hospitalization.

Introducción. La hospitalización de un hijo en la unidad de pacientes críticos neonatal puede ser altamente estresante para padres y madres, lo cual se intensificó en el contexto de la pandemia por COVID-19. A la fecha, no se han encontrado estudios que describan la experiencia de padres que vivieron la doble hospitalización simultánea de su pareja y de su hijo/a al nacer, durante la pandemia por COVID-19. Objetivos. Explorar la vivencia de los padres de tener a sus hijos/as hospitalizados en Neonatología mientras su pareja se encontraba hospitalizada por agravamiento de COVID-19. Población y método. Cuatro entrevistas semiestructuradas fueron realizadas y analizadas mediante un análisis interpretativo fenomenológico. Resultados. Se identificaron cuatro momentos cuando surgieron emociones específicas: a) inicio del contagio, b) hospitalización de la pareja, c) nacimiento del bebé y d) hospitalización del bebé. Culpa, miedo, angustia de muerte, soledad e incertidumbre aparecen muy tempranamente y luego se combinan con emociones como felicidad y empoderamiento, entre otras. La falta de contacto físico con sus parejas e hijos, y las fallas en la comunicación con los equipos de salud se destacan como factores que obstaculizan el ejercicio del rol paternal, mientras que una comunicación fluida con el equipo y una participación activa en los cuidados del bebé son factores protectores. Los padres cumplen una multiplicidad de roles, en la que prima el rol protector. Conclusiones. La comunicación y la atención centrada en la familia, y la participación activa en los cuidados de los bebés tienen el potencial de proteger contra el impacto de esta experiencia compleja de doble hospitalización.

Study of the human hippocampal formation: a method for histological and magnetic resonance correlation in perinatal cases.

Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this exploration is increasingly used, which requires defining visible HF landmarks on MRI images, validated through histological analysis. This study aims to provide a protocol to identify HF landmarks on MRI images, followed by histological validation through serial sections of the temporal lobe of the samples examined, to assess the longitudinal extent of the hippocampus during the perinatal period. We examined ex vivo MRI images from nine infant control brain samples. Histological validation of the hippocampal formation MRI images was obtained through serial sectioning and examination of Nissl-stained sections at 250 µm intervals along the entire length of the hippocampal formation. Up to six landmarks were identified both in MRI images and the serial histological sections. Proceeding in an anterior to posterior (rostrocaudal) direction, these were as follows: 1) the limen insulae (fronto-temporal junction); 2) the beginning of the amygdaloid complex; 3) the beginning of the lateral ventricle; 4) the caudal limit of the uncus, indicated by the start of the lateral geniculate nucleus (at the level of the gyrus intralimbicus); 5) the end of the lateral geniculate nucleus (beginning of the pulvinar); and 6) the beginning of the fornix. After histological validation of each of these landmarks, the full longitudinal length of the hippocampal formation and distances between landmarks were calculated. No statistically significant differences were found in total length or between landmarks. While the HF is anatomically organized at birth, its annotation is particularly challenging to perform. The histological validation of HF landmarks allows a better understanding of MRI images. The proposed protocol could be useful to assess MRI hippocampal quantification in children and possible variations due to different neurological diseases.

Autocrine/Paracrine Slit-Robo Signaling Controls Optic Lobe Development in Drosophila melanogaster.

Cell segregation mechanisms play essential roles during the development of the central nervous system (CNS) to support its organization into distinct compartments. The Slit protein is a secreted signal, classically considered a paracrine repellent for axonal growth through Robo receptors. However, its function in the compartmentalization of CNS is less explored. In this work, we show that Slit and Robo3 are expressed in the same neuronal population of the Drosophila optic lobe, where they are required for the correct compartmentalization of optic lobe neuropils by the action of an autocrine/paracrine mechanism. We characterize the endocytic route followed by the Slit/Robo3 complex and detected genetic interactions with genes involved in endocytosis and actin dynamics. Thus, we report that the Slit-Robo3 pathway regulates the morphogenesis of the optic lobe through an atypical autocrine/paracrine mechanism in addition to its role in axon guidance, and in association with proteins of the endocytic pathway and small GTPases.

An Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms and dopaminergic cell loss. A pre-symptomatic phase characterized by non-motor symptoms precedes the onset of motor alterations. Two recent PET studies in human carriers of mutations associated with familial PD demonstrate an early serotonergic commitment-alteration in SERT binding-before any dopaminergic or motor dysfunction, that is, at putative PD pre-symptomatic stages. These findings support the hypothesis that early alterations in the serotonergic system could contribute to the progression of PD, an idea difficult to be tested in humans. Here, we study some components of the serotonergic system during the pre-symptomatic phase in a well-characterized Drosophila PD model, Pink1B9 mutant flies. We detected lower brain serotonin content in Pink1B9 flies, accompanied by reduced activity of SERT before the onset of motor dysfunctions. We also explored the consequences of a brief early manipulation of the serotonergic system in the development of motor symptoms later in aged animals. Feeding young Pink1B9 flies with fluoxetine, a SERT blocker, prevents the loss of dopaminergic neurons and ameliorates motor impairment observed in aged mutant flies. Surprisingly, the same pharmacological manipulation in young control flies results in aged animals exhibiting a PD-like phenotype. Our findings support that an early dysfunction in the serotonergic system precedes and contributes to the onset of the Parkinsonian phenotype in Drosophila.

Group motivational intervention in overweight/obese patients in primary prevention of cardiovascular disease in the primary healthcare area.

BACKGROUND: The global mortality caused by cardiovascular disease increases with weight. The Framingham study showed that obesity is a cardiovascular risk factor independent of other risks such as type 2 diabetes mellitus, dyslipidemia and smoking. Moreover, the main problem in the management of weight-loss is its maintenance, if it is achieved. We have designed a study to determine whether a group motivational intervention, together with current clinical practice, is more efficient than the latter alone in the treatment of overweight and obesity, for initial weight loss and essentially to achieve maintenance of the weight achieved; and, secondly, to know if this intervention is more effective for reducing cardiovascular risk factors associated with overweight and obesity. METHODS: This 26-month follow up multi-centre trial, will include 1200 overweight/obese patients. Random assignment of the intervention by Basic Health Areas (BHA): two geographically separate groups have been created, one of which receives group motivational intervention (group intervention), delivered by a nurse trained by an expert phsychologist, in 32 group sessions, 1 to 12 fortnightly, and 13 to 32, monthly, on top of their standard program of diet, exercise, and the other (control group), receiving the usual follow up, with regular visits every 3 months. DISCUSSION: By addressing currently unanswered questions regarding the maintenance in weight loss in obesity/overweight, upon the expected completion of participant follow-up in 2012, the IMOAP trial should document, for the first time, the benefits of a motivational intervention as a treatment tool of weight loss in a primary care setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01006213.

Acompañar una doble hospitalización en pandemia: la experiencia de padres con bebés hospitalizados mientras las madres se encuentran hospitalizadas por COVID-19 / Supporting a double hospitalization during the pandemic: The experience of fathers whose infants were hospitalized while their mothers were also hospitalized due to COVID-19

Introducción. La hospitalización de un hijo en la unidad de pacientes críticos neonatal puede ser altamente estresante para padres y madres, lo cual se intensificó en el contexto de la pandemia por COVID-19. A la fecha, no se han encontrado estudios que describan la experiencia de padres que vivieron la doble hospitalización simultánea de su pareja y de su hijo/a al nacer, durante la pandemia por COVID-19. Objetivos. Explorar la vivencia de los padres de tener a sus hijos/as hospitalizados en Neonatología mientras su pareja se encontraba hospitalizada por agravamiento de COVID-19. Población y método. Cuatro entrevistas semiestructuradas fueron realizadas y analizadas mediante un análisis interpretativo fenomenológico. Resultados. Se identificaron cuatro momentos cuando surgieron emociones específicas: a) inicio del contagio, b) hospitalización de la pareja, c) nacimiento del bebé y d) hospitalización del bebé. Culpa, miedo, angustia de muerte, soledad e incertidumbre aparecen muy tempranamente y luego se combinan con emociones como felicidad y empoderamiento, entre otras. La falta de contacto físico con sus parejas e hijos, y las fallas en la comunicación con los equipos de salud se destacan como factores que obstaculizan el ejercicio del rol paternal, mientras que una comunicación fluida con el equipo y una participación activa en los cuidados del bebé son factores protectores. Los padres cumplen una multiplicidad de roles, en la que prima el rol protector. Conclusiones. La comunicación y la atención centrada en la familia, y la participación activa en los cuidados de los bebés tienen el potencial de proteger contra el impacto de esta experiencia compleja de doble hospitalización.

Introduction. The hospitalization of a baby in the neonatal intensive care unit may be highly stressful for both mothers and fathers, and this was even more intense in the context of the COVID-19 pandemic.To date, no studies have been found that describe the experience of fathers who underwent the simultaneous hospitalization of their partner and newborn infant during the COVID-19 pandemic. Objectives. To explore the experience of fathers who had their babies hospitalized in the Neonatal Unit while their partner were hospitalized due to worsening of COVID-19. Population and method. Four semi-structured interviews were conducted and analyzed using an interpretative phenomenological analysis. Results. Four moments were identified when specific emotions arose: a) onset of infection, b) partner hospitalization, c) baby birth, and d) baby hospitalization. Guilt, fear, death anxiety, loneliness, and uncertainty appear very early and are later combined with emotions such as happiness and empowerment, among others. The lack of physical contact with their partners and babies and failures in communication with the health care team stand out as factors that hinder the exercise of the paternal role, while an effective communication with the health care team and active participation in the baby's care are protective factors. Fathers fulfill multiple roles, the most important of which is their role as protectors. Conclusions. Family-centered communication and care and active involvement in baby care may potentially protect against the impact of this complex experience of double hospitalization.

Percepción del dolor durante el trabajo de parto. Una revisión de los factores involucrados / Pain perception during labor. A review of factors

The pain experimented by women during the labor is considered as one of the most important, significative and stressing events in the life of a woman. It is widely known than labour is the caused of severe pain. Our purpose is to review the aspects related to the experience of acute pain of patients in labor, related to the normal physiology in this process and to describe different variables that can modify it. From the evidence we conclude that perception of pain is subjective and variable, and it is influenced or modified for multiple factors, by past living experiences or transmitted through generations, by socio-cultural environment and individual expectative in front of this event, also by psychological, clinical, biochemical and genetic factors that predispose to experience a different perception of its severity. This information seems relevant to us for a better comprehension of pain during the labor and for developing strategies that would allowed a relief in a more effective way helping the maternal-fetal welfare and a better experience of maternity, especially during labor.

El dolor experimentado por mujeres durante el trabajo de parto es considerado uno de los eventos más importantes, significativos e intensos en la vida de una mujer. Es ampliamente conocido que el trabajo de parto es causa de un dolor severo. Nuestro propósito es revisar los aspectos relacionados a la experiencia del dolor agudo en las pacientes en trabajo de parto, en cuanto a la fisiología normal de este proceso y describir diferentes variables que pueden modificarlo. Desde la revisión bibliográfica concluimos que la percepción del dolor es subjetiva y variable, y está influenciada o modificada por múltiples factores, por las experiencias pasadas vividas o transmitidas entre generaciones, por el entorno sociocultural y las expectativas individuales ante este evento, también por factores psicológicos, clínicos, bioquímicos y genéticos que predisponen a experimentar una percepción diferente en cuanto a su severidad y significado. Esta información nos parece relevante para una mejor compresión del dolor en el parto y para desarrollar estrategias que permitan su alivio de manera más efectiva, contribuyendo al bienestar materno-fetal y a una mejor experiencia de la maternidad, especialmente durante el trabajo de parto.

Involucramiento del padre en la crianza: una mirada triádica de las relaciones familiares tempranas / Paternal involvement in child rearing: a triadic view of early family interactions

Considerando los beneficios de una paternidad activa en el desarrollo de niños y niñas, así como en las dinámicas familiares en general, los profesionales del área de la salud deben ser agentes activos en la promoción de la participación de madres y padres en la crianza. El siguiente artículo busca introducir en el contexto nacional una herramienta que amplía la mirada del desarrollo infantil y las relaciones al interior de la familia, desde la díada a la tríada. El Lausanne Trilogue Play (LTP) es una herramienta observacional, desarrollada por Fivaz Depeursinge, Frascarolo y Corboz-Warnery (1996) que permite la evaluación estandarizada de la “alianza familiar”, corroborando la importancia de incorporar al padre en los estudios de procesos e interacciones familiares, así como la existencia de un efecto familiar tríadico desde etapas tempranas...

Considering the benefits that an active paternity has in child development and in general family dynamics, health professionals should be active agents in promoting maternal and paternal care. The following article seeks to introduce in the national context an instrument that contributes in enlarging the perspective in child development and family relationships, from the dyad to the triad. The Lausanne Trilogue Play (LTP) is an observational tool, developed by Fivaz-Depeursinge, Frascarolo y Corboz-Warnery (1996) that allows a standardized evaluation from the “family alliance”, corroborating the importance of incorporating the father in the studies of family process and interactions, as well as the existence of a triadic family effect since early stages...