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Dementia increases dependence in older adults and decreases their quality of life and that of their family members. These family members often take on the responsibility of caregiving and suffer from burden and health deterioration due to facing various stressors. The aim is to verify the effectiveness of existing interventions aimed at relieving the burden and stress of informal caregivers of older people with dementia. A scoping review was conducted by consulting the Web of Science, Scopus, ProQuest, and PubMed databases, following the guidelines of the PRISMA 2020 Statement. The review protocol has been registered in PROSPERO under number CRD42024558609. Twenty-six articles met the inclusion criteria and were reviewed, studying the type of intervention design, the sample size of caregivers and their main characteristics, the duration and follow-up, and the variables investigated with their respective measurement instruments. The analysis of the different studies showed that the most developed types of interventions are psychoeducational and cognitive-behavioral therapies, both individual and group. These interventions were mainly effective in reducing the burden and depressive symptoms of caregivers. It is considered advisable to implement more randomized controlled trials for further research, because as the number of caregivers increases, so does the need for affordable and effective interventions.

Abstract Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.

Hungry animals consistently show a desire to obtain food. Even a brief sensory detection of food can trigger bursts of physiological and behavioral changes. However, the underlying mechanisms by which the sensation of food triggers the acute behavioral response remain elusive. We have previously shown in Drosophila that hunger drives a preference for low temperature. Because Drosophila is a small ectotherm, a preference for low temperature implies a low body temperature and a low metabolic rate. Here, we show that taste-sensing triggers a switch from a low to a high temperature preference in hungry flies. We show that taste stimulation by artificial sweeteners or optogenetics triggers an acute warm preference, but is not sufficient to reach the fed state. Instead, nutrient intake is required to reach the fed state. The data suggest that starvation recovery is controlled by two components: taste-evoked and nutrient-induced warm preferences, and that taste and nutrient quality play distinct roles in starvation recovery. Animals are motivated to eat based on time of day or hunger. We found that clock genes and hunger signals profoundly control the taste-evoked warm preferences. Thus, our data suggest that the taste-evoked response is one of the critical layers of regulatory mechanisms representing internal energy homeostasis and metabolism.

Depressive and anxiety disorders constitute some of the most prevalent mental disorders around the world. For years, the development of new lead compounds for drug discovery in this field has been an area of great attention. Recently, a series of tetrahydrocarbazole derivatives have demonstrated important anxiolytic-like activity, associated with their structures and stereochemistry. Here, we present a study of the antidepressant effect and anxiolytic-like activity of a fused thiopyrano-piperidone-tetrahydrocarboline (compound 4). The antidepressant and anxiolytic-like effects of 4 (1–50 mg/kg p.o.) were assessed with the tail suspension test and the hole-board test, respectively. This study determined the possible mechanisms involved in the anxiolytic-like actions of 4 using inhibitors or neurotransmission and evaluated its interaction with 5HT2A receptors using a molecular docking study. As an analog to the tetrahydrocarbazole core, the tetrahydrocarboline derivative showed anxiolytic-like activity (ED50 = 13 mg/kg p.o.) in the hole-board test, with a comparable effect to the reference drug, 1.5 mg/kg clonazepam, with the possible participation of the serotonergic system.

Academic procrastination, a prevalent issue in higher education, has been associated with various adverse outcomes. This study aims to discern and compare the degrees of academic procrastination among university students in Honduras and Spain while also investigating the relationship between academic procrastination and the Big Five personality factors alongside self-esteem. The sample comprised 457 university students, encompassing 237 Hondurans and 220 Spaniards. The research employed descriptive, comparative, correlational, and regression analyses. Honduran university students exhibited a significantly lower level of academic procrastination. Correlational analyses revealed that self-esteem and all Big Five personality factors, except for neuroticism in the Spanish cohort, displayed noteworthy associations with academic procrastination. Further regression analyses demonstrated that conscientiousness emerged as a significant predictor of procrastination in both samples. This study's findings can be pivotal in identifying students at risk of procrastination at an early stage. Additionally, the results can inform the development of intervention programs designed to mitigate procrastination tendencies among university students.

Introducción: Niveles altos de estrés pueden provocar el burnout con efectos negativos para la persona, siendo más acusado y frecuente en ámbitos laborales como el docente. Asimismo, la inteligencia emocional y el estilo de humor se relacionan con su aparición, duración e intensidad. Objetivo: Analizar este síndrome en docentes, así como el grado de predicción que la inteligencia emocional y los estilos de humor tienen en él. Método: Se utilizará un diseño de tipo predictivo transversal. La muestra se compone de 196 docentes. Resultados: Se encontró una relación entre aspectos de la inteligencia emocional y los estilos de humor con el burnout. El análisis de regresión mostró que la regulación emocional predice en parte el burnout profesional y que la evaluación de las propias emociones y el humor afiliativo explican parte del burnout relacionado con el alumnado. Discusión: La inteligencia emocional, especialmente la relacionada con el uso y la regulación de las emociones, y el estilo de humor adaptativo se relacionan de forma negativa y predicen un menor burnout en los docentes, por lo que estos podrían beneficiarse de la capacitación en inteligencia emocional como parte de las estrategias de prevención y tratamiento.

Actualmente, se ha producido un gran desarrollo tecnológico y el uso de internet entre los jóvenes está ampliamente presente. Si bien el uso adecuado de Internet puede tener consecuencias positivas en diferentes ámbitos, una utilización excesiva e incontrolada se ha asociado con numerosos resultados negativos. El objetivo de este estudio es estudiar la prevalencia del uso problemático de internet (UPI) en estudiantes universitarios hondureños y en identificar variables sociodemográficas y de personalidad asociadas al UPI. La muestra estuvo compuesta por 791 estudiantes universitarios. Se han realizado análisis descriptivos, correlaciones y comparativos. Los resultados ponen de manifiesto elevadas tasas de UPI en los estudiantes universitarios, mayor entre las mujeres, y que el UPI se asocia con un alto grado de neuroticismo y con bajos niveles de extraversión, cordialidad, responsabilidad, apertura a la experiencia y autoestima. En conclusión, este estudio ofrece información sobre factores relacionados con el UPI que pueden aumentar las posibilidades de una temprana detección e intervención.

The aim of this study was to investigate the potential of Amaranthus cruentus flavonoids (quercetin, kaempferol, catechin, hesperetin, naringenin, hesperidin, and naringin), cinnamic acid derivatives (p-coumaric acid, ferulic acid, and caffeic acid), and benzoic acids (vanillic acid and 4-hydroxybenzoic acid) as antioxidants, antidiabetic, and antihypertensive agents. An analytical method for simultaneous quantification of flavonoids, cinnamic acid derivatives, and benzoic acids for metabolomic analysis of leaves and inflorescences from A. cruentus was developed with HPLC-UV-DAD. Evaluation of linearity, limit of detection, limit of quantitation, precision, and recovery was used to validate the analytical method developed. Maximum total flavonoids contents (5.2 mg/g of lyophilized material) and cinnamic acid derivatives contents (0.6 mg/g of lyophilized material) were found in leaves. Using UV-Vis spectrophotometry, the maximum total betacyanin contents (74.4 mg/g of lyophilized material) and betaxanthin contents (31 mg/g of lyophilized material) were found in inflorescences. The leaf extract showed the highest activity in removing DPPH radicals. In vitro antidiabetic activity of extracts was performed with pancreatic α-glucosidase and intestinal α-amylase, and compared to acarbose. Both extracts exhibited a reduction in enzyme activity from 57 to 74%. Furthermore, the in vivo tests on normoglycemic murine models showed improved glucose homeostasis after sucrose load, which was significantly different from the control. In vitro antihypertensive activity of extracts was performed with angiotensin-converting enzyme and contrasted to captopril; both extracts exhibited a reduction of enzyme activity from 53 to 58%. The leaf extract induced a 45% relaxation in an ex vivo aorta model. In the molecular docking analysis, isoamaranthin and isogomphrenin-I showed predictive binding affinity for α-glucosidases (human maltase-glucoamylase and human sucrase-isomaltase), while catechin displayed binding affinity for human angiotensin-converting enzyme. The data from this study highlights the potential of A. cruentus as a functional food.

Problematic Internet use has become a major problem worldwide due to its numerous negative correlates in the field of health, both mental and physical, and its increasing prevalence, making it necessary to study both its risk and protective factors. Several studies have found a negative relationship between resilience and problematic Internet use, although the results are inconsistent. This meta-analysis assesses the relationship between problematic Internet use and resilience, and analyses its possible moderating variables. A systematic search was conducted in PsycInfo, Web of Science and Scopus. A total of 93,859 subjects from 19 studies were included in the analyses. The results show that there is a statistically-significant negative relationship (r = −0.27 (95% CI [−0.32, −0.22])), without evidence of publication bias. This meta-analysis presents strong evidence of the relationship between the two variables. Limitations and practical implications are discussed.

El objetivo de esta investigación fue analizar el papel que los factores de personalidad pertenecientes a los Cinco Grandes y la Tríada Oscura —maquiavelismo, narcisismo y psicopatía— tienen en la conducción agresiva. La muestra se compuso de 318 estudiantes universitarios con permiso de conducir, quienes contestaron a una batería de pruebas que evaluaba los fac-tores de personalidad de los Cinco Grandes (tipi), la Tríada Oscura (dd) y la conducción agresiva (das y dax). Los análisis de regresión jerárquica controlando las variables de edad y sexo, respaldan la utilidad predictiva de los factores de persona-lidad de los Cinco Grandes y la Tríada Oscura. Los resultados mostraron cómo la afabilidad, la estabilidad emocional y la apertura a la experiencia predicen de manera significativa diversos aspectos de la conducción agresiva. El maquiavelismo y el narcisismo son predictores significativos de diversas formas de expresión de la ira en la conducción, una vez controlados los efectos de los Cinco Grandes.

Abstract 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.

Rhythmic feeding activity has become an important research area for circadian biologists as it is now clear that metabolic input is critical for regulating circadian rhythms, and chrononutrition has been shown to promote health span. In contrast to locomotor activity rhythm, studies conducting high throughput analysis of Drosophila rhythmic food intake have been limited and few monitoring system options are available. One monitoring system, the Fly Liquid-Food Interaction Counter (FLIC) has become popular, but there is a lack of efficient analysis toolkits to facilitate scalability and ensure reproducibility by using unified parameters for data analysis. Here, we developed Circadian Rhythm Using Mealtime Behavior (CRUMB), a user-friendly Shiny app to analyze data collected using the FLIC system. CRUMB leverages the ‘plotly’ and ‘DT’ packages to enable interactive raw data review as well as the generation of easily manipulable graphs and data tables. We used the main features of the FLIC master code provided with the system to retrieve feeding events and provide a simplified pipeline to conduct circadian analysis. We also replaced the use of base functions in time-consuming processes such as ‘rle’ and ‘read.csv’ with faster versions available from other packages to optimize computing time. We expect CRUMB to facilitate analysis of feeding-fasting rhythm as a robust output of the circadian clock.

The purpose of this investigation was to study the relationship between sleep quality, problematic smartphone use (PSU) and bedtime procrastination, as well as to assess gender and age differences. A total of 313 participants, aged 18–60 (M = 30 ± 10.1; 53.2% males), completed an online survey between February and May 2023 in Spain. The Pittsburgh Sleep Quality Index, Smartphone Addiction Scale-Short Version and Bedtime Procrastination Scale were used to measure sleep quality, PSU and bedtime procrastination, respectively. Additionally, smartphone use habits were evaluated through self-report questions. Pearson correlations, independent samples t-tests, one-way ANOVA, Bonferroni’s post hoc tests and mediation analysis were conducted. Correlation analysis showed positive associations between the three main variables. Independent sample t-tests indicated females were more prone to PSU along with higher overall smartphone use. Post hoc analysis of one-way ANOVA exposed age differences between young adults (18–25 years old), adults (26–44 years old) and middle-aged adults (45–60 years old) in PSU and bedtime procrastination. Finally, mediation analysis revealed that PSU had indirect effects on sleep quality through bedtime procrastination, but no direct effects on sleep quality. Therefore, PSU, and especially bedtime procrastination, should be considered as targets in future campaigns or intervention programs to improve sleep quality among the young Spanish population.

Circadian clock and chromatin-remodeling complexes are tightly intertwined systems that regulate rhythmic gene expression. The circadian clock promotes rhythmic expression, timely recruitment, and/or activation of chromatin remodelers, while chromatin remodelers regulate accessibility of clock transcription factors to the DNA to influence expression of clock genes. We previously reported that the BRAHMA (BRM) chromatin-remodeling complex promotes the repression of circadian gene expression in Drosophila. In this study, we investigated the mechanisms by which the circadian clock feeds back to modulate daily BRM activity. Using chromatin immunoprecipitation, we observed rhythmic BRM binding to clock gene promoters despite constitutive BRM protein expression, suggesting that factors other than protein abundance are responsible for rhythmic BRM occupancy at clock-controlled loci. Since we previously reported that BRM interacts with two key clock proteins, CLOCK (CLK) and TIMELESS (TIM), we examined their effect on BRM occupancy to the period (per) promoter. We observed reduced BRM binding to the DNA in clk null flies, suggesting that CLK is involved in enhancing BRM occupancy to initiate transcriptional repression at the conclusion of the activation phase. Additionally, we observed reduced BRM binding to the per promoter in flies overexpressing TIM, suggesting that TIM promotes BRM removal from DNA. These conclusions are further supported by elevated BRM binding to the per promoter in flies subjected to constant light and experiments in Drosophila tissue culture in which the levels of CLK and TIM are manipulated. In summary, this study provides new insights into the reciprocal regulation between the circadian clock and the BRM chromatin-remodeling complex.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography–mass spectrometry (GC–MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1–50 mg/kg p.o.) and DHS (0.1–10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1–50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

Animals adapt their seasonal physiology by measuring photoperiodic changes over the calendar year. A new study in PLOS Biology uncovers changes in glutamate dynamics in the bean bug that are dependent on photoperiod and a clock gene.

Introducción: Esta investigación apunta en la dirección de la pertinencia y utilidad de diseñar y aplicar intervenciones focalizadas en la mejora de las inteligencias, atendiendo de manera prioritaria a los aspectos emocionales y creativos, para fomentar un rendimiento integral óptimo en los estudiantes. Existe una pronunciada necesidad de formar a personas competentes, tanto cognitiva como socioemocionalmente, para que se desenvuelvan de manera eficaz en una sociedad en constante cambio. Objetivo: El propósito fue evaluar y comparar el nivel de autoeficacia que perciben los participantes con respecto a sus inteligencias múltiples, su inteligencia emocional, su creatividad y su rendimiento académico. Método: La muestra se compone de 435 estudiantes universitarios de primer curso. El diseño de investigación fue predictivo transversal. Resultados: Se hallaron relaciones entre las variables analizadas, así como diferencias en función del sexo de los participantes. Los análisis de regresión muestran cómo las inteligencias lingüística y la lógico-matemática autopercibidas son predictores del rendimiento académico de los estudiantes. Discusión: Se detecta una relación positiva entre las diferentes competencias sociales y emocionales, así como la importancia de las mismas para el óptimo rendimiento de los estudiantes.

Traffic crashes are one of the main causes of mortality in the world. Driving anger and aggressive driving are risk factors frequently related to traffic crashes. Emotional intelligence has been recognized as a predictive factor for various types of aggressive behaviors. The aim of this paper was to analyze the role of emotional intelligence on aggressive driving and traffic violations. 318 undergraduates with driver license (82.5% females) aged between 19 and 27 years (M=20.77, SD=1.39) completed a survey battery measuring emotional intelligence (TMMS-24), traffic violations (DBQ), driving anger (DAS) and aggressive driving (DAX). Hierarchical regressions controlling respondent age and gender supported the predictive utility of Emotional Intelligence over traffic violations and mode of expressing anger while driving, especially adaptive expression. So, improving drivers Emotional Intelligence may be useful in preventing these risky driving behaviors

Abstract Schizophrenia shows high heritability and several of the genes associated with this disorder are involved in calcium (Ca2+) signalling and synaptic function. One of these is the Rab-3 interacting molecule-1 (RIM1), which has recently been associated with schizophrenia by Genome Wide Association Studies (GWAS). However, its contribution to the pathophysiology of this disorder remains unexplored. In this work, we use Drosophila mutants of the orthologue of RIM1, Rim, to model some aspects of the classical and non-classical symptoms of schizophrenia. Rim mutants showed several behavioural features relevant to schizophrenia including social distancing and altered olfactory processing. These defects were accompanied by reduced evoked Ca2+ influx and structural changes in the presynaptic terminals sent by the primary olfactory neurons to higher processing centres. In contrast, expression of Rim-RNAi in the mushroom bodies (MBs), the main memory centre in flies, spared learning and memory suggesting a differential role of Rim in different synapses. Circadian deficits have been reported in schizophrenia. We observed circadian locomotor activity deficits in Rim mutants, revealing a role of Rim in the pacemaker ventral lateral clock neurons (LNvs). These changes were accompanied by impaired day/night remodelling of dorsal terminal synapses from a subpopulation of LNvs and impaired day/night release of the circadian neuropeptide pigment dispersing factor (PDF) from these terminals. Lastly, treatment with the commonly used antipsychotic haloperidol rescued Rim locomotor deficits to wildtype. This work characterises the role of Rim in synaptic functions underlying behaviours disrupted in schizophrenia.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1–10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light–dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Abstract Globally, neonicotinoids are the most used insecticides, despite their well-documented sub-lethal effects on beneficial insects. Neonicotinoids are nicotinic acetylcholine receptor agonists. Memory, circadian rhythmicity and sleep are essential for efficient foraging and pollination and require nicotinic acetylcholine receptor signalling. The effect of field-relevant concentrations of the European Union-banned neonicotinoids: imidacloprid, clothianidin, thiamethoxam and thiacloprid were tested on Drosophila memory, circadian rhythms and sleep. Field-relevant concentrations of imidacloprid, clothianidin and thiamethoxam disrupted learning, behavioural rhythmicity and sleep whilst thiacloprid exposure only affected sleep. Exposure to imidacloprid and clothianidin prevented the day/night remodelling and accumulation of pigment dispersing factor (PDF) neuropeptide in the dorsal terminals of clock neurons. Knockdown of the neonicotinoid susceptible Dα1 and Dβ2 nicotinic acetylcholine receptor subunits in the mushroom bodies or clock neurons recapitulated the neonicotinoid like deficits in memory or sleep/circadian behaviour respectively. Disruption of learning, circadian rhythmicity and sleep are likely to have far-reaching detrimental effects on beneficial insects in the field.

Este trabajo evalúa los resultados de un programa para la mejora de la adaptación socioemocional del alumnado. Se analiza, por un lado, el perfil socializador (construido en base a las competencias socioemocionales desarrolladas en el programa) y su relación con el rendimiento académico y, por otro, la existencia de diferencias de género en dicho perfil. Participaron 198 estudiantes de educación primaria (103 varones (52%) y 95 mujeres (48%) –M= 8.68 años; DT= 1.75-) y 18 docentes (5 varones (28%) y 13 mujeres (72%) –M= 48.83 años; DT= 4.27-). Se aplicó la batería de socialización BAS-1. Se utilizó metodología descriptiva, comparativa y correlacional. Se realizaron análisis descriptivos, comparativos, de correlación y de regresión lineal múltiple. La muestra presenta un perfil de socialización altamente facilitador, que se relaciona con el rendimiento académico. Se encontraron diferencias en los aspectos facilitadores de la socialización a favor de las niñas, mientras que, en los aspectos inhibidores, únicamente se detectaron diferencias en agresividad-terquedad, siendo superior en los niños. Esta investigación apunta hacia la eficacia y pertinencia del programa debido a los efectos positivos detectados.

Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography–mass spectrometry (GC-MS). This study evaluated the effects of CAE (10–100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED50 = 57 mg/kg). CAE (10–100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.

Schizophrenia exhibits up to 80% heritability. A number of genome wide association studies (GWAS) have repeatedly shown common variants in voltage-gated calcium (Cav) channel genes CACNA1C, CACNA1I and CACNA1G have a major contribution to the risk of the disease. More recently, studies using whole exome sequencing have also found that CACNA1B (Cav2.2 N-type) deletions and rare disruptive variants in CACNA1A (Cav2.1 P/Q-type) are associated with schizophrenia. The negative symptoms of schizophrenia include behavioural defects such as impaired memory, sleep and circadian rhythms. It is not known how variants in schizophrenia-associated genes contribute to cognitive and behavioural symptoms, thus hampering the development of treatment for schizophrenia symptoms. In order to address this knowledge gap, we studied behavioural phenotypes in a number of loss of function mutants for the Drosophila ortholog of the Cav2 gene family called cacophony (cac). cac mutants showed several behavioural features including decreased night-time sleep and hyperactivity similar to those reported in human patients. The change in timing of sleep-wake cycles suggested disrupted circadian rhythms, with the loss of night-time sleep being caused by loss of cac just in the circadian clock neurons. These animals also showed a reduction in rhythmic circadian behaviour a phenotype that also could be mapped to the central clock. Furthermore, reduction of cac just in the clock resulted in a lengthening of the 24 h period. In order to understand how loss of Cav2 function may lead to cognitive deficits and underlying cellular pathophysiology we targeted loss of function of cac to the memory centre of the fly, called the mushroom bodies (MB). This manipulation was sufficient to cause reduction in both short- and intermediate-term associative memory. Memory impairment was accompanied by a decrease in Ca2+ transients in response to a depolarizing stimulus, imaged in the MB presynaptic terminals. This work shows loss of cac Cav2 channel function alone causes a number of cognitive and behavioural deficits and underlying reduced neuronal Ca2+ transients, establishing Drosophila as a high-throughput in vivo genetic model to study the Cav channel pathophysiology related to schizophrenia.

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.

As in vertebrates, dopaminergic neural systems are key regulators of motor programs in insects, including the fly Drosophila melanogaster. Dopaminergic systems innervate the Mushroom Bodies (MB), an important association area in the insect brain primarily associated to olfactory learning and memory, but that has been also implicated with the execution of motor programs. The main objectives of this work is to assess the idea that dopaminergic systems contribute to the execution of motor programs in Drosophila larvae, and then, to evaluate the contribution of specific dopaminergic receptors expressed in MB to these programs. Our results show that animals bearing a mutation in the dopamine transporter show reduced locomotion, while mutants for the dopaminergic biosynthetic enzymes or the dopamine receptor Dop1R1 exhibit increased locomotion. Pan-neuronal expression of an RNAi for the Dop1R1 confirmed these results. Further studies show that animals expressing the RNAi for Dop1R1 in the entire MB neuronal population or only in the MB γ-lobe forming neurons, exhibit an increased motor output, as well. Interestingly, our results also suggest that other dopaminergic receptors do not contribute to larval motor behavior. Thus, our data support the proposition that CNS dopamine systems innervating MB neurons modulate larval locomotion and that Dop1R1 mediates this effect.

Heliangolide-type sesquiterpene lactones (HTSLs) are phytocompounds with several pharmacological activities including cytotoxic and antitumor activity. Both bioactivities are related to an α-methylene-γ-lactone moiety and an ester group on carbon C-8 in the sesquiterpene lactone (SL) structure. Two HTSLs, incomptines A (AI) and B (IB) isolated from Decachaeta incompta, were evaluated for their cytotoxic activity on three leukemia cell lines: HL-60, K-562, and REH cells. Both compounds were subjected to a molecular docking study using target proteins associated with cancer such as topoisomerase IIα, topoisomerase IIβ, dihydrofolate reductase, methylenetetrahydrofolate dehydrogenase, and Bcl-2-related protein A1. Results show that IA and IB exhibit cytotoxic activity against all cell lines used. The CC50 value of IA was 2–4-fold less than etoposide and methotrexate, two anticancer drugs used as positive controls. The cytotoxic activity of IB was close to that of etoposide and methotrexate. The molecular docking analysis showed that IA and IB have important interaction on all targets used. These findings suggest that IA and IB may serve as scaffolds for the development of new treatments for different types of leukemia.

Incomptines A (IA) and B (IB) are two sesquiterpene lactones with antiprotozoal, antibacterial, cytotoxic, antitumor, spermicidal, and phytotoxic properties. The antibacterial activity of IA and IB against bacteria causing diarrhoea have been reported; however, no information is available regarding their antibacterial activity on Vibrio cholerae. In this work, both compounds were evaluated for their anti-diarrhoeal potential using the bacterium V. cholerae, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) analysis on cholera toxin, and a cholera toxin-induced diarrhoea model in male Balb/c mice. In addition, a molecular docking study was carried out to understand the interaction of IA and IB with cholera toxin. In terms of antibacterial activity, IB was three times more active than IA on V. cholerae. In the case of SDS-PAGE analysis and the in silico study, IA was most effective, revealing its potential binding mode at a molecular level. In terms of anti-diarrhoeal activity, IA was 10 times more active than IB and racecadotril, an antisecretory drug used as positive control; the anti-diarrheal activity of IB was also closer than racecadotril. The results obtained from in vitro, in vivo, and computational studies on V. cholerae and cholera toxin support the potential of IA and IB as new anti-diarrhoeal compounds.

Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1–4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.

Este estudio analizó los accidentes de motocicleta y ciclomotor en Barcelona (España). 53.190 informes de conductores de motocicleta y ciclomotor involucrados en accidentes entre los años 2006 y 2011 fueron extraídos de la base de datos de accidentes con víctimas de la Dirección General de Tráfico. Estos datos fueron analizados en términos de sexo, grupos de edad, motivo del desplazamiento, día de la semana, infracciones de velocidad, uso del casco y lesividad, con el objetivo de estudiar las características de los accidentes de motocicleta y ciclomotor en Barcelona y evaluar las diferencias entre conductores varones y mujeres en estos accidentes. La gravedad de los accidentes sufridos por conductores varones es superior a la de las mujeres. Se encontraron diferencias significativas en todas las variables consideradas en el estudio, lo que implica diferencias en el perfil del conductor de accidentado.

The cellular underpinnings of memory deficits in Alzheimer’s disease (AD) are poorly understood. We utilized the tractable neural circuits sub-serving memory in Drosophila to investigate the role of impaired Ca2+ handling in memory deficits caused by expression of human 0N4R isoform of tau which is associated with AD. Expression of tau in mushroom body neuropils, or a subset of mushroom body output neurons, led to impaired memory. By using the Ca2+ reporter GCaMP6f, we observed changes in Ca2+ signaling when tau was expressed in these neurons, an effect that could be blocked by the L-type Ca2+ channel antagonist nimodipine or reversed by RNAi knock-down of the L-type channel gene. The L-type Ca2+ channel itself is required for memory formation, however, RNAi knock-down of the L-type Ca2+ channel in neurons overexpressing human tau resulted in flies whose memory is restored to levels equivalent to wild-type. Expression data suggest that Drosophila L-type Ca2+ channel mRNA levels are increased upon tau expression in neurons, thus contributing to the effects observed on memory and intracellular Ca2+ homeostasis. Together, our Ca2+ imaging and memory experiments suggest that expression of the 0N4R isoform of human tau increases the number of L-type Ca2+ channels in the membrane resulting in changes in neuronal excitability that can be ameliorated by RNAi knockdown or pharmacological blockade of L-type Ca2+ channels. This highlights a role for L-type Ca2+ channels in tauopathy and their potential as a therapeutic target for AD.

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

Ephedra is one of the largest genera of the Ephedraceae family, which is distributed in arid and semiarid regions of the world. In the traditional medicine from several countries some species from the genus are commonly used to treat asthma, cold, flu, chills, fever, headache, nasal congestion, and cough. The chemical constituents of Ephedra species have been of research interest for decades due to their contents of ephedrine-type alkaloids and its pharmacological properties. Other chemical constituents such as phenolic and amino acid derivatives also have resulted attractive and have provided evidence-based supporting of the ethnomedical uses of the Ephedra species. In recent years, research has been expanded to explore the endophytic fungal diversity associated to Ephedra species, as well as, the chemical constituents derived from these fungi and their pharmacological bioprospecting. Two additional aspects that illustrate the chemical diversity of Ephedra genus are the chemotaxonomy approaches and the use of ephedrine-type alkaloids as building blocks in organic synthesis. American Ephedra species, especially those that exist in Mexico, are considered to lack ephedrine type alkaloids. In this sense, the phytochemical study of Mexican Ephedra species is a promising area of research to corroborate their ephedrine-type alkaloids content and, in turn, discover new chemical compounds with potential biological activity. Therefore, the present review represents a key compilation of all the relevant information for the Ephedra genus, in particular the American species, the species distribution, their ecological interactions, its ethnobotany, its phytochemistry and their pharmacological activities and toxicities, in order to promote clear directions for future research.

Un reto de la educación actual es formar a alumnos competentes para desenvolverse en una sociedad diversa y dinámica. El cociente intelectual no es suficiente para garantizar el éxito académico ni profesional (Extremera & Fernández-Berrocal, 2006) y deben considerarse aspectos cognitivos, sociales y emocionales. El objetivo del estudio fue analizar el grado alcanzado en estudiantes universitarios de trabajo social en las inteligencias múltiples, inteligencia emocional, creatividad y rendimiento académico, así como su relación y las diferencias en función del sexo y el curso en una muestra de 100 estudiantes. Se encontraron diferencias significativas en función del curso y relaciones entre algunos componentes emocionales e inteligencias múltiples. Así, los resultados hallados ponen de manifiesto la relevancia y relación entre las variables evaluadas para el rendimiento global de los estudiantes universitarios y, por tanto, la pertinencia y necesidad de diseñar intervenciones dirigidas a la optimización de las mismas de manera integrada.

Los accidentes de motocicleta son uno de los problemas de seguridad vial más importantes a nivel mundial. Hay una escasez de estudios específicos sobre las características de la accidentalidad de las motocicletas de tipo scooter, motivada por la falta de una definición precisa de este tipo de motocicleta y de la identificación de los distintos tipos de vehículos de dos ruedas en los registros de accidentes. El objetivo de este trabajo es determinar las características de los 293 conductores de motocicletas scooter fallecidos en España durante el periodo 2006-2011. Se realizaron análisis descriptivos y de asociación en función de la naturaleza de las variables. Los resultados de los análisis permiten identificar algunos de los principales factores humanos asociados a los accidentes mortales de los conductores de motocicletas scooter.

In this article there talks each other the discussion that exists concerning the utility of the exercises of paper and pencil, being this one of the principal weakness in the contemporary school. That's why it begins formulating a typical exercise of kinematics, in which there for is asked the student a simple reasoning of a concrete situation, later it is analyzed which would be the possible solutions to the enunciated situation, and then the statement transforms in a problem of research adding parameters, variables and modifying the purpose of the questions, this way a problematic situation appears in the what one the student will be capable of choosing the fundamental aspects to solve it, in such a way that this one adopts an attitude adequate before a research process. Finally a perfectible solution appears in accordance with the scheme used by the student to verify it experimentally.

En este artículo se trata la discusión que hay en torno a la utilidad de los ejercicios de lápiz y papel, siendo estos una de las principales falencias en la escuela contemporánea. Por eso se inicia formulando un ejercicio típico de cinemática, en el cual se pide al estudiante un razonamiento simple de una situación concreta, después se analiza cuáles serían las posibles respuestas a la situación enunciada, y luego se transforma el enunciado en un problema de investigación añadiendo parámetros, variables y modificando la intencionalidad de las preguntas, de esta manera se plantea una situación problemática en la cual el estudiante será capaz de elegir los aspectos fundamentales para resolverla, de tal forma que éste adopte una actitud adecuada ante un proceso investigativo. Por último se plantea una solución perfectible de acuerdo al esquema empleado por el estudiante para verificarla experimentalmente.

The title compound, C10H11NO5, is of interest with respect to its antidyslipidemic activity. It was prepared by reaction of 4-nitrophenol with ethyl 2-bromo-2-methylpropionate followed by ethyl ester hydrolysis. In the crystal, molecules are linked into centrosymmetric dimers by intermolecular O—H...O hydrogen bonds and the dimers are connected into chains by weak C—H...O interactions. The packing is further stabilized by offset π–π interactions between adjacent benzene rings with a centroid–centroid distance of 3.8643 (17) Å.

Rhythmic feeding activity has become an important research area for circadian biologists as it is now clear that metabolic input is critical for regulating circadian rhythms, and chrononutrition has been shown to promote health span. In contrast to locomotor activity rhythm, studies conducting high throughput analysis of Drosophila rhythmic food intake have been limited and few monitoring system options are available. One monitoring system, the Fly Liquid-Food Interaction Counter (FLIC) has become popular, but there is a lack of efficient analysis toolkits to facilitate scalability and ensure reproducibility by using unified parameters for data analysis. Here, we developed Circadian Rhythm Using Mealtime Behavior (CRUMB), a user-friendly Shiny app to analyze data collected using the FLIC system. CRUMB leverages the ‘plotly’ and ‘DT’ packages to enable interactive raw data review as well as the generation of easily manipulable graphs and data tables. We used the main features of the FLIC master code provided with the system to retrieve feeding events and provide a simplified pipeline to conduct circadian analysis. We also replaced the use of base functions in time-consuming processes such as ‘rle’ and ‘read.csv’ with faster versions available from other packages to optimize computing time. We expect CRUMB to facilitate analysis of feeding-fasting rhythm as a robust output of the circadian clock.

Rhythmic feeding activity has become an important research area for circadian biologists as it is now clear that metabolic input is critical for regulating circadian rhythms, and chrononutrition has been shown to promote health span. In contrast to locomotor activity rhythm, studies conducting high throughput analysis of Drosophila rhythmic food intake have been limited and few monitoring system options are available. One monitoring system, the Fly Liquid-Food Interaction Counter (FLIC) has become popular, but there is a lack of efficient analysis toolkits to facilitate scalability and ensure reproducibility by using unified parameters for data analysis. Here, we developed Circadian Rhythm Using Mealtime Behavior (CRUMB), a user-friendly Shiny app to analyze data collected using the FLIC system. CRUMB leverages the ‘plotly’ and ‘DT’ packages to enable interactive raw data review as well as the generation of easily manipulable graphs and data tables. We used the main features of the FLIC master code provided with the system to retrieve feeding events and provide a simplified pipeline to conduct circadian analysis. We also replaced the use of base functions in time-consuming processes such as ‘rle’ and ‘read.csv’ with faster versions available from other packages to optimize computing time. We expect CRUMB to facilitate analysis of feeding-fasting rhythm as a robust output of the circadian clock.