APOE genotype, hippocampal volume, and cognitive reserve predict improvement by cognitive training in older adults without dementia: a randomized controlled trial.

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90 min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R2 = .19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R2 = .18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R2 = .07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R2 = .087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors.Trial registration: Trial retrospectively registered on January 29th, 2020-(ClinicalTrials.gov -NCT04245579).

Predictive factors and risk and protection groups for loneliness in older adults: a population-based study.

BACKGROUND: Loneliness is considered a public health problem, particularly among older adults. Although risk factors for loneliness have been studied extensively, fewer studies have focused on the protected and risk groups that these factors configure. Our objective is to analyze the variables and latent factors that predict loneliness in older adults and that enable risk and protected groups to be configured. METHODS: We employed an epidemiological, cross-sectional survey that was carried out on a random sample of 2060 people over 65 years extracted from the census. A structured telephone interview was used to assess mental and physical health, habits, quality of life, and loneliness, applying the COOP-Wonca, Goldberg General Health (GHQ-12), and Barber Questionnaires. RESULTS: Predictors of loneliness were: mental health, living alone, quality of life, depressive symptoms, low educational level, and some deficiency situations such as having no one to turn to for help. The factors extracted (Factorial Analysis) were: a subjective experience of poor health, objective isolation, and psychological isolation. We established at risk and protected groups ("Decision Tree" procedure), and loneliness was referred to by 73.2% of the people living alone and with poor mental health and quality of life (risk group). By contrast, only 0.8% of people living with others, with good mental health and good quality of life felt loneliness (protected group). CONCLUSION: In a well-developed city, subjective and objective factors are associated with loneliness. These factors, especially those associated with at risk or protected groups, must be considered to develop strategies that address loneliness.

Direct Synthesis of MOF-74 Materials on Carbon Fiber Electrodes for Structural Supercapacitors.

The use of fossil fuels has contributed significantly to environmental pollution and climate change. For this reason, the development of alternative energy storage devices is key to solving some of these problems. The development of lightweight structures can significantly reduce the devices' weight, thereby reducing energy consumption and emissions. Combining lightweight structures with alternative energy storage technologies can further improve efficiency and performance, leading to a cleaner and more sustainable system. In this work, for the first time, MOF-74 materials with different divalent metal ions have been synthesized directly on carbon fiber, one of the most widely used materials for the preparation of electrodes for supercapacitors with structural properties. Different techniques, such as nitrogen adsorption-desorption isotherms, cyclic voltammetry or galvanostatic charge-discharge, among others, were used to evaluate the influence of the metal cation on the electrochemical capacitance behavior of the modified electrodes. The Co-MOF-74 material was selected as the best modification of the carbon fibers for their use as electrodes for the fabrication of structural supercapacitors. The good electrochemical performance shown after the incorporation of MOF materials on carbon fibers provides a viable method for the development of carbon fiber electrodes, opening a great variety of alternatives.

Social Loneliness in Older Adults with Mild Cognitive Impairment: Predictive Factors and Associated Clinical Characteristics.

BACKGROUND: Loneliness and social isolation are considered public health problems among older individuals. In addition, both increase the risk of developing cognitive impairment and dementia. The Social Loneliness construct has been proposed to refer to these harmful social interaction-related factors. OBJECTIVE: To define the risk factors of Social Loneliness in individuals with mild cognitive impairment (MCI) and to analyze cognitive, emotional, and functional differences according to the participant's degree of Social Loneliness. METHODS: Through convenience sampling, 105 participants over 60 diagnosed with MCI were selected. The evaluation consisted of anamnesis and a comprehensive neuropsychological examination. The ESTE-II questionnaire was used to assess Social Loneliness and its three factors: perceived social support, social participation, and use of communication technologies. Personality was measured with the NEO-FFI questionnaire. RESULTS: The predictors of the Social Loneliness factors were as follows; 1) perceived social support (R2 = 0.33): Neuroticism (ß= 0.353), depression (ß= 0.205), and perceived health (ß= 0.133); 2) social participation (R2 = 0.24): Conscientiousness (ß= -0.344) and Extraversion (ß= -0.263); 3) use of communication technologies (R2 = 0.44): age (ß= 0.409), type of cohabitation (ß= 0.331), cognitive reserve (ß= -0.303), and Conscientiousness (ß= -0.247); all p < 0.05. The participants with a higher degree of Social Loneliness showed more depressive symptoms (R2 = 0.133), more memory complaints (R2 = 0.086), worse perceived health (R2 = 0.147), lower attentional performance/processing speed (R2 = 0.094), and more naming difficulties (R2 = 0.132); all p < 0.05. CONCLUSIONS: This research represents an advance in detecting individuals with MCI and an increased risk of developing Social Loneliness, which influences the configuration of the clinical profile of MCI.

The New Nematicide Cyclobutrifluram Targets the Mitochondrial Succinate Dehydrogenase Complex in Caenorhabditis elegans.

Today, agriculture around the world is challenged by parasitic nematode infections. Plant-parasitic nematodes (PPNs) can cause significant damage and crop loss and are a threat to food security. For a long time, the management of PPN infection has relied on nematicides that impact not only parasitic nematodes but also other organisms. More recently, new nematicides have been developed that appear to specifically target PPN. Cyclobutrifluram belongs to this new category of nematicides. Using the nematode Caenorhabditis elegans as a model organism, we show here that cyclobutrifluram strongly impacts the survival and fertility rates of the worm by decreasing the number of germ cells. Furthermore, using a genetic approach, we demonstrate that cyclobutrifluram functions by inhibiting the mitochondrial succinate dehydrogenase (SDH) complex. Transcriptomic analysis revealed a strong response to cyclobutrifluram exposure. Among the deregulated genes, we found genes coding for detoxifying proteins, such as cytochrome P450s and UDP-glucuronosyl transferases (UGTs). Overall, our study contributes to the understanding of the molecular mode of action of cyclobutrifluram, to the finding of new approaches against nematicide resistance, and to the discovery of novel nematicides. Furthermore, this study confirms that C. elegans is a suitable model organism to study the mode of action of nematicides.

Specific Neurodynamic Exercises on Pain and Disability in Old Women with Chronic Mechanical Neck Pain: A Randomized Controlled Trial.

Neurodynamic exercise is a specific type of exercise used as a neural treatment that focuses on restoring altered homeostasis in the neuroimmune system by mobilising the nervous system and other structures. A prospective, randomized clinical trial was performed to evaluate the effect of neurodynamic exercises on disability and neck pain in elderly women over four weeks. Participants were randomized into two groups: a neurodynamic (NM) group (n = 28) and a non-specific exercise (NSE) group (n = 28). Inclusion criteria were women over 65 years of age who subjectively admitted to having mechanical neck pain for more than six months. Results showed that specific neurodynamic exercises can improve pain and disability in older women with chronic mechanical neck pain. Improvements were observed in all variables (p < 0.05). Significant between-group differences in favour of the NM group were only found for neck pressure pain thresholds and both tibialis anterior muscles. Larger effect sizes were obtained in favour of the NM group, especially for pain, disability, neck extension and inclination and pressure pain thresholds. Neurodynamic exercises have been shown to be more clinically relevant in disability and neck pain in older women.

Effects of Self-Efficacy and Outcome Expectations on Motor Imagery-Induced Thermal and Mechanical Hypoalgesia: A Single-Blind Randomised Controlled Trial.

The main aim of this study was to assess whether self-efficacy (SE) and outcome expectations (OEs) modulate the hypoalgesic effect induced by motor imagery (MI). A total of 75 asymptomatic participants were randomly assigned to the positive (SE+, OE+), negative (SE-, OE-) or non-expectation (CG) groups. Heat pain threshold (HPT) and pain pressure threshold (PPT) were the main variables. Cold detection threshold (CDT), warm detection threshold (WDT), heart rate (HR) and perceived fatigue were the secondary variables. The variables were assessed preintervention, immediately postintervention and 10 min postintervention, except for HR, which was measured continuously during the intervention. Regarding HPT, significant within-group pre-post differences were found in the OE+ group, with a low effect size (p = 0.01, d = -0.39). With regard to ΔPPT, significant intergroup differences were found in Δpost-pre between the SE+ and CG groups (p = 0.012, d = 1.04) and also between SE+ and OE- (p = 0.006, d = 1.08), both with a large effect size. CG, SE-, and OE- groups had poorer CDT and WDT. Regarding HR, significant intergroup differences were found in the postintervention measurement between OE+ and SE-, with a large effect size (p = 0.016, d = 1.34). Lastly, no between-group differences were found regarding perceived fatigue (p > 0.05). The results obtained showed that positive expectations have a slight influence on the increase in heat and mechanical pain detection thresholds. Positive and non-expectancy groups showed an autonomic activation. The results also showed that negative expectations led to poorer perceptual processes.

Genetic Predictors of Change in Episodic Verbal Memory by Cognitive Intervention: ACT, PICALM, BDNF, NRG1, APOE Genes and Their Interactions in Situations of Cognitive Demand.

BACKGROUND: Cognitive interventions (CIs) in the elderly are activities that seek to improve cognitive performance and delay its deterioration. Our objectives were to study potential genetic predictors of how a CI program may influence immediate and delayed episodic verbal memory (EVM). METHODS: 162 participants were elderly individuals without dementia who were randomized into parallel control and experimental groups. Participants underwent genetic testing to analyze the PICALM, ACT, NRG1, BDNF and APOE genes. We performed a broad neuropsychological assessment before and 6 months after the CI. The CI involved multifactorial training (30 sessions). The control group undertook the centre's standard activities. The main outcome measures were the genotype studied as a predictor of post-intervention changes in EVM. RESULTS: We found the CI was associated with improvements in several cognitive functions, including immediate and delayed EVM. While no individual gene was associated with any such change, the interaction between PICALM/ACT (p = 0.008; Eta2 = 0.23) and PICALM/NRG1 (p = 0.029; Eta2 = 0.19) was associated with improved immediate EVM, and the NRG1/BDNF interaction was associated with improved delayed EVM (p = 0.009; Eta2 = 0.21). The APOEε4 genotype was not associated with any change in EVM. CONCLUSIONS: Our study shows that the participants' genotype can have an impact on the results of CIs. Cognitive stress may stimulate the interaction of various genes and as such, different types of CI should be established for distinct groups of people taking into account the individual's characteristics, like genotype, to improve the results of this type of health prevention and promotion activity.

Loneliness in the elderly: association with health variables, pain, and cognitive performance. A population-based study / La soledad en personas mayores: asociación con las variables de salud, el dolor y el rendimiento cognitivo. Estudio poblacional

The aim of this population-based study is to analyze the association of loneliness and physical health, pain, health-related quality of life, mental health, cognitive performance, morbidity, and use of health services. Based on the census, a stratified random sampling was chosen. A telephone interview was conducted with 2,060 people over 65 years old, using the GHQ-12 and the COOP-Wonca. An association of loneliness with General Mental Health (GHQ-12) was found, OR = 1.43 (1.34, 1.52) and depression, OR = 2.34 (1.54, 3.53). In cognitive performance the highest effect variable was “memory problems disturb your daily life”, OR = 3.11 (1.25, 7.72); illnesses-related variables: the highest effect variables were perception of health status, OR = 1.37 (1.13, 1. 67) and quality of life (COOP-Wonca), OR = 3.03 (2.32, 3.94); pain-related variables: the highest effect variables were non-localized pain, OR = 2.67 (1.87, 3.83) and arthritis/arthrosis, OR = 1.94 (1.38, 2.72); impaired vision, OR = 2. 62 (1.84, 3.73) and hearing, OR = 1.81 (1.21, 2.72). It is concluded that loneliness is a complex phenomenon associated with variables of different nature. This fact should be taken into account at the time of planning possible solutions. (AU)

El objetivo de este estudio poblacional es analizar la asociación de la soledad no deseada (SND) con salud física, dolor, calidad de vida relacionada con la salud, salud mental, rendimiento cognitivo, morbilidad y uso de servicios de salud. Recurriendo al censo, se realizó un muestreo aleatorio estratificado en Madrid. Se llevó a cabo una entrevista telefónica a 2,060 mayores de 65 años utilizando el GHQ-12 y el COOP-Wonca. Encontramos asociación de la SND y la salud mental general (GHQ-12), OR = 1.43 (1.34, 1.52) y depresión, OR = 2.34 (1.54, 3.53). En rendimiento cognitivo, la variable de mayor efecto fue “los problemas de memoria alteran su vida cotidiana”, OR = 3.11 (1.25, 7.72); variables relacionadas con enfermedad: las de mayor efecto fueron “percepción del estado de salud”, OR = 1.37 (1.13, 1.67) y calidad de vida (COOP-Wonca), OR = 3.03 (2.32, 3.94); variables de dolor: dolor general, OR = 2.67 (1.87, 3.83) y artritis/artrosis, OR = 1.94 (1.38, 2.72); dificultades para ver, OR = 2.62 (1.84, 3.73) y oír, OR = 1.81 (1.21, 2.72). Se concluye que la SND es una situación compleja, lo que debe considerarse al programar soluciones que sean efectivas. (AU)

Factors influencing mesenchymal stromal cells in in vitro cellular models to study retinal pigment epithelial cell rescue.

Mesenchymal stromal cells (MSC) stop or slow retinal pigment epithelium (RPE) and neuroretina (NR) degeneration by paracrine activity in oxidative stress-induced retinal degenerative diseases. However, it is mandatory to develop adequate in vitro models that allow testing new treatment strategies against oxidative stress before performing in vivo studies. The viable double- and triple-layered setups are composed of separate layers of NR, MSC, and RPE (NR-MSC-RPE, NR-RPE, MSC-RPE) partially mimic in vivo retinal conditions. In this study, the paracrine neuroprotective effect of each setup's microenvironment on hydrogen peroxide (H2O2)-stressed was compared with unstressed RPE cells. RPE cell proliferation viability was assessed on day 1, 3, and 6 using Alamar Blue® (10%), MTT (10%) and a cell viability/cytotoxicity assay kit followed by data analysis. The results showed that RPE cells, highly viable (> 90%) in mixed medium of DMEM and neurobasal A (1:1), lost 50% viability on exposure to 400 µM of H2O2 (P < 0.05). The unexposed groups differed significantly from exposed groups for RPE cell growth (RPE and [Formula: see text]RPE (P < 0.0001), NR-MSC-RPE, and NR-MSC-[Formula: see text]RPE (P < 0.05), NR-RPE and NR-[Formula: see text]RPE (P < 0.01), and MSC-RPE and MSC-[Formula: see text]RPE (P < 0.01). NR-[Formula: see text]RPE and NR-RPE supported RPE cell proliferation viability better than other setups (P < 0.01) and RPE cells proliferated 0.49-fold more in NR-MSC-[Formula: see text]RPE than NR-MSC-RPE. Thus, NR and MSC presence improved significantly each setup's microenvironment for cell rescue, nevertheless, each setup also showed limitations for its use as an in vitro study tool. Health of microenvironment of such setups depends on many factors including cell-secreted trophic factors.

The zinc-finger transcription factor LSL-1 is a major regulator of the germline transcriptional program in Caenorhabditis elegans.

Specific gene transcriptional programs are required to ensure the proper proliferation and differentiation processes underlying the production of specialized cells during development. Gene activity is mainly regulated by the concerted action of transcription factors and chromatin proteins. In the nematode Caenorhabditis elegans, mechanisms that silence improper transcriptional programs in germline and somatic cells have been well studied, however, how are tissue-specific sets of genes turned on is less known. LSL-1 is herein defined as a novel crucial transcriptional regulator of germline genes in C. elegans. LSL-1 is first detected in the P4 blastomere and remains present at all stages of germline development, from primordial germ cell proliferation to the end of meiotic prophase. lsl-1 loss-of-function mutants exhibit many defects including meiotic prophase progression delay, a high level of germline apoptosis, and production of almost no functional gametes. Transcriptomic analysis and ChIP-seq data show that LSL-1 binds to promoters and acts as a transcriptional activator of germline genes involved in various processes, including homologous chromosome pairing, recombination, and genome stability. Furthermore, we show that LSL-1 functions by antagonizing the action of the heterochromatin proteins HPL-2/HP1 and LET-418/Mi2 known to be involved in the repression of germline genes in somatic cells. Based on our results, we propose LSL-1 to be a major regulator of the germline transcriptional program during development.

Microglia: The Real Foe in HIV-1-Associated Neurocognitive Disorders?

The current use of combined antiretroviral therapy (cART) is leading to a significant decrease in deaths and comorbidities associated with human immunodeficiency virus type 1 (HIV-1) infection. Nonetheless, none of these therapies can extinguish the virus from the long-lived cellular reservoir, including microglia, thereby representing an important obstacle to curing HIV. Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS) and are believed to be involved in the development of HIV-1-associated neurocognitive disorder (HAND). At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that removing these infected cells from the brain, as well as obtaining a better understanding of the specific molecular mechanisms of HIV-1 latency in these cells, should help in the design of new strategies to prevent HAND and achieve a cure for these diseases. The goal of this review was to study the current state of knowledge of the neuropathology and research models of HAND containing virus susceptible target cells (microglial cells) and potential pharmacological treatment approaches under investigation.

Métodos diagnósticos de VPH para la prevención del cáncer cérvico uterino en Ecuador

Resumen El cáncer cérvico uterino (CCUes la segunda causa de muerte en mujeres entre los 35 y 64 años en Ecuador. La intervención en salud sugiere el diagnóstico temprano de la infección con el Virus del Papiloma Humano (VPH) y el estado citológico de células epiteliales cervicales. El VPH se considera la causa etiológica principal del 99 % del CCU. Objetivo . Valorar el diagnóstico del CCU a partir del empleo de métodos citológicos y moleculares en mujeres de Ecuador. Métodos . Revisión sistemática sobre diagnóstico de VPH y prevención del CCU. La búsqueda abarcó artículos originales en inglés y español desde 2010-2020. Se emplearon bases de datos como Pudmed, Scielo, Elsevier, Redalyc y Scopus. Resultados . La citología como método de tamizaje primario ha disminuido la incidencia de CCU, aunque su baja sensibilidad pone límites a la eficacia. La implementación de métodos moleculares ha permitido detectar diferentes genotipos y obtener confiabilidad en los resultados, pero su accesibilidad se encuentra limitada en poblaciones con bajos recursos financieros. El poco conocimiento y la aplicación de métodos heterogéneos dificultan que se realice un diagnóstico temprano como prevención de la infección y su relación con el CCU. Conclusiones . El diagnóstico certero del CCU es una necesidad urgente en el ámbito ecuatoriano. La combinación de métodos como el PAP y los métodos moleculares de identificación del VPH pueden ser herramientas suficientes a tal efecto. La valoración adecuada de la técnica de genotipificación a emplear es relevante con la finalidad de asegurar un método de diagnóstico sensible, específico y accesible a la mujer ecuatoriana.

Abstract Cervical uterine cancer (CUC) is considered the second cause of death in women between the ages of 35 and 64 in Ecuador. Health intervention suggests early diagnosis of Human Papillomavirus (HPV) infection and cytological status of cervical epithelial cells. HPV is considered the main etiological cause of 99% of CCU. Objective . To assess the diagnosis of CCU from the use of cytological and molecular methods in women from Ecuador. Methods . Thematic review on HPV diagnosis and CCU prevention. The search covered original articles in English and Spanish from 2010-2020. Databases such as Pudmed, Scielo, Elsevier, Redalyc, Scopus were used. Resulted . Cytology as a primary screening method has decreased the incidence of CCU, although its low sensitivity limits efficacy. The implementation of molecular methods has made it possible to detect different genotypes and obtain reliability in the results, but their accessibility is limited in populations with low financial resources. The little knowledge and the application of heterogeneous methods makes it difficult to make an early diagnosis to prevent infection and its relationship with CCU. Conclusions . The accurate diagnosis of CCU is an urgent need in the Ecuadorian environment. The combination of methods such as PAP and molecular methods for HPV identification may be sufficient tools for this purpose. Adequate assessment of the genotyping technique to be used is relevant in order to ensure a sensitive, specific and accessible diagnostic method for Ecuadorian women.

Resumo O câncer cervical uterino (CUC) é considerado a segunda causa de morte em mulheres entre 35 e 64 anos no Equador. A intervenção em saúde sugere o diagnóstico precoce da infecção pelo papilomavírus humano (HPV) e o estado citológico das células epiteliais cervicais. O HPV é considerado a principal causa etiológica de 99% das UCC. Objetivo : Avaliar o diagnóstico de CCU a partir do uso de métodos citológicos e moleculares em mulheres equatorianas. Métodos . Revisão temática sobre diagnóstico de HPV e prevenção de CCU. A pesquisa cobriu artigos originais em inglês e espanhol de 2010-2020. Bancos de dados como Pudmed, Scielo, Elsevier, Redalyc, Scopus foram usados. Resultados . A citologia como método de rastreamento primário diminuiu a incidência de CCU, embora sua baixa sensibilidade limite a eficácia. A implementação de métodos moleculares tem permitido detectar diferentes genótipos e obter confiabilidade nos resultados, mas sua acessibilidade é limitada em populações com poucos recursos financeiros. O pouco conhecimento e a aplicação de métodos heterogêneos dificultam o diagnóstico precoce para prevenção da infecção e sua relação com o CCU. Conclusões : O diagnóstico preciso do CCU é uma necessidade urgente no meio ambiente equatoriano. A combinação de métodos como PAP e métodos moleculares para identificação do HPV podem ser ferramentas suficientes para esse fim. A avaliação adequada da técnica de genotipagem a ser utilizada é relevante para garantir um método diagnóstico sensível, específico e acessível para as mulheres equatorianas.

Futuras líneas de investigación en cuidados sobre dolor, sedación, contenciones y delirium en el paciente crítico / Future lines of research on pain care, sedation, restraints and delirium in the critically ill patient

La valoración y manejo del dolor-analgesia, agitación-sedación, contenciones mecánicas (CM) y delirium en el paciente critico ha ido evolucionando en los últimos años, tal y como recogen las recomendaciones de las Guías de Práctica Clínica (GPC) 1. Sin embargo, todavía quedan cuestiones pendientes, en las que las enfermeras pueden investigar destacando el efecto que los cuidados pueden tener en los resultados de salud sensibles a la práctica enfermera. A continuación, se proponen doce líneas de investigación en cuidados para la orientación de futuros proyectos sobre dolor, sedación, CM y delirium. (AU)

Subjective Memory Complaints in healthy older adults: Fewer complaints associated with depression and perceived health, more complaints also associated with lower memory performance.

OBJECTIVES: (i) To analyze if general cognitive performance, perceived health and depression are predictors of Subjective Memory Complaints (SMC) contrasting their effect sizes; (ii) to analyze the relationship between SMC and objective memory by comparing a test that measures memory in daily life and a classical test of associated pairs; (iii) to examine if different subgroups, formed according to the MFE score, might have different behaviors regarding the studied variables. METHODS: Sample: 3921 community-dwelling people (mean age 70.41±4.70) without cognitive impairment. Consecutive non-probabilistic recruitment. ASSESSMENT: Mini Cognitive Exam (MCE), daily memory Rivermead Behavioural Memory Test (RBMT), Paired Associates Learning (PAL), Geriatric Depression Scale (GDS), Nottingham Health Profile (NHP). Dependent variable: Memory Failures Everyday Questionnaire (MFE). RESULTS: Two different dimensions to explain SMC were found: One subjective (MFE, GDS, NHP) and other objective (RBMT, PAL, MCE), the first more strongly associated with SMC. SMC predictors were NHP, GDS, RBMT and PAL, in this order according to effect size. Considering MFE scores we subdivided the sample into three groups (low, medium, higher scores): low MFE group was associated with GDS; medium, with GDS, NPH and RBMT, and higher, with age as well. Effect size for every variable tended to grow as the MFE score was higher. CONCLUSION: SMC were associated with both health profile and depressive symptoms and, in a lesser degree, with memory and overall cognitive performance. In people with fewer SMC, these are only associated with depressive symptomatology. More SMC are associated with depression, poor health perception and lower memory.

A genetically encoded biosensor for visualising hypoxia responses in vivo.

Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia) rely on the conserved hypoxia-inducible factor 1 (HIF-1). Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD) of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response.

A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells.

PURPOSE: To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. METHODS: RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. RESULTS: Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. CONCLUSIONS: A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies.

The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts.

Centrosome asymmetry has been implicated in stem cell fate maintenance in both flies and vertebrates, but the underlying molecular mechanisms are incompletely understood. Here, we report that loss of CG7337, the fly ortholog of WDR62, compromises interphase centrosome asymmetry in fly neural stem cells (neuroblasts). Wdr62 maintains an active interphase microtubule-organizing center (MTOC) by stabilizing microtubules (MTs), which are necessary for sustained recruitment of Polo/Plk1 to the pericentriolar matrix (PCM) and downregulation of Pericentrin-like protein (Plp). The loss of an active MTOC in wdr62 mutants compromises centrosome positioning, spindle orientation, and biased centrosome segregation. wdr62 mutant flies also have an ∼40% reduction in brain size as a result of cell-cycle delays. We propose that CG7337/Wdr62, a microtubule-associated protein, is required for the maintenance of interphase microtubules, thereby regulating centrosomal Polo and Plp levels. Independent of this function, Wdr62 is also required for the timely mitotic entry of neural stem cells.