Evolution of the Quinoline Scaffold for the Treatment of Leishmaniasis: A Structural Perspective.

Since the beginning of the XXI century, Leishmaniasis has been integrated into the World Health Organization's list of the 20 neglected tropical diseases, being considered a public health issue in more than 88 countries, especially in the tropics, subtropics, and the Mediterranean area. Statistically, this disease presents a world prevalence of 12 million cases worldwide, with this number being expected to increase shortly due to the 350 million people considered at risk and the 2-2.5 million new cases appearing every year. The lack of an appropriate and effective treatment against this disease has intensified the interest of many research groups to pursue the discovery and development of novel treatments in close collaboration with the WHO, which hopes to eradicate it shortly. This paper intends to highlight the quinoline scaffold's potential for developing novel antileishmanial agents and provide a set of structural guidelines to help the research groups in the medicinal chemistry field perform more direct drug discovery and development programs. Thus, this review paper presents a thorough compilation of the most recent advances in the development of new quinoline-based antileishmanial agents, with a particular focus on structure-activity relationship studies that should be considerably useful for the future of the field.

Chronotype and Time of Day Effects on a Famous Face Recognition Task with Dynamic Stimuli.

Chronotype and Time of Day (ToD) can modulate several aspects of cognitive performance. However, there is limited evidence about the effect of these variables on face recognition performance, so the aim of the present study is to investigate this influence. For this, 274 participants (82.5% females; age 18-49 years old, mean = 27.2, SD = 1.82) were shown 20 short videoclips, each gradually morphing from a general identity unfamiliar face to a famous face. Participants should press the spacebar to stop each video as soon as they could identify the famous face, and then provide the name or an unequivocal description of the person. Analysis of response times (RT) showed that evening-types recognised the faces faster than morning-types. Considering different ToD windows, the effect of chronotype was only significant in the 13h-17h and in the 21h-6h time-windows. Altogether, results suggest an advantage of evening-types on famous face recognition using dynamic stimuli with morning-types, being particularly slower during their non-optimal period.

El cronotipo y la hora del día pueden modular varios aspectos del rendimiento cognitivo. Sin embargo, existen pocas pruebas sobre el efecto de estas variables en el rendimiento en el reconocimiento de caras, por lo que el objetivo del presente estudio es investigar esta influencia. Para ello, se mostraron a 274 participantes (82.5% mujeres; edad 18-49 años, media = 27.2, DE = 1.82) 20 videoclips cortos, cada uno de los cuales pasaba gradualmente de una cara desconocida de identidad general a una cara famosa. Los participantes debían pulsar la barra espaciadora para detener cada vídeo en cuanto pudieran identificar la cara famosa y, a continuación, proporcionar el nombre o una descripción inequívoca de la persona. El análisis de los tiempos de respuesta (TR) mostró que los participantes vespertinos reconocían las caras más rápidamente que los matutinos. Considerando diferentes ventanas de hora del día, el efecto del cronotipo solo fue significativo en las ventanas temporales de 13h-17h y de 21h-6h. En conjunto, los resultados sugieren una ventaja de los tipos vespertinos en el reconocimiento de caras famosas al utilizar estímulos dinámicos, siendo los tipos matutinos particularmente más lentos durante su periodo no óptimo.

Initial Psychological Reactions to COVID-19 of Middle Adolescents in Portugal.

In its early stage, the COVID-19 pandemic and the subsequent public health measures brought several challenges to people in general, with adolescents being one of the most affected groups. To assess the psychological reactions of Portuguese adolescents in that early phase of the COVID-19 pandemic, we conducted an online survey that was filled by a sample of 340 (67.6% female and 32.4% male) middle adolescents (aged 16 and 17 years). Using the Impact Event Scale-Revised and the Depression, Anxiety, and Stress Scale, we found that most participants reported a normal score for depression, anxiety, and stress. However, 47.1% reported some level of pandemic-related traumatic distress, and 25.6% reported high severity values. The girls' levels of depression, anxiety, stress, and traumatic distress were significantly higher than those of the boys. Regression models showed that gender, number of symptoms experienced in the past days, self-reported health status, and concern with family were significant predictors of these mental health indicators. Our findings underscore the need for future research on the long-term traumatic psychological impact of the COVID-19 pandemic in adolescents, and on the gender differences in this group. This will allow the development of strategies to identify and address at-risk adolescents, since the promotion of mental health and the prevention of pathology are imperative for the health of current and future generations.

Structure-Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes.

Leishmaniasis is one of the most neglected diseases in modern times, mainly affecting people from developing countries of the tropics, subtropics and the Mediterranean basin, with approximately 350 million people considered at risk of developing this disease. The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures-there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure-activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N1,N12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 ± 0.11 µM, EC50 = 11.69 ± 3.96 µM and TI = 19.48).

The Impact of Sleep on Face Recognition Memory: A Scoping Review.

Sleep has a major impact on a variety of human biological and cognitive functions. In particular, its impact on memory has attracted extensive research and has been amply demonstrated. However, it is still unclear whether sleep, or lack thereof, affects the ability to recognize faces. To clarify this, we conducted a scoping review on studies that included a face recognition memory task and any kind of sleep manipulation in adults without any sleep pathology. A systematic search and synthesis of peer-reviewed journal articles identified through the electronic databases Scopus, Web of Science, EBSCO, and PubMed was performed. A final sample of 18 articles, corresponding to 19 studies, met the eligibility criteria. The results of 13 articles suggested that sleep benefited face recognition ability, whereas two articles indicated a detrimental effect of sleep on performance, and four articles found no significant effects. This review highlights the high methodological variability between studies, in terms of sleep manipulation, retention interval, tasks used to probe face recognition, and other variables. In sum, although around one third of the studies show a beneficial effect of sleep on memory for faces, we suggest that future research should invest in replicating these findings with a stricter control of potentially confounding variables to allow stronger conclusions to be drawn.

Impact of a Virtual Reality-Based Simulation on Empathy and Attitudes Toward Schizophrenia.

Virtual Reality (VR) has been identified as one of the most promising resources for developing empathy towards stigmatized groups as it allows individuals to experience a situation close to reality from another person's perspective. This quasi-experimental study aimed to examine the impact on empathy, knowledge, and attitudes towards people with schizophrenia of a VR simulation that reproduces the experience of psychotic symptoms while performing a cognitive task compared with watching a 2D video and, thus, how these experiences could reduce stigma towards people diagnosed with schizophrenia. The sample comprised of 102 higher education health students, distributed by the experimental and control groups. The impact of the program was measured by completing multiple questionnaires on levels of empathy, attitudes, and mental health knowledge. Both methods (VR and 2D video) were, to a certain extent, effective. However, VR was more effective at eliciting attitudes and knowledge change compared to the control group. These findings suggest that not only VR but also 2D videos could be interesting strategies to enhance empathy and improve attitudes towards people with schizophrenia in higher education health students.

Perceived Vulnerability to Disease Questionnaire: psychometric validation with a Portuguese sample.

BACKGROUND: Individual differences in one's perceived vulnerability to infectious diseases are implicated in psychological distress, social and behavioral disease avoidance phenomena. The Perceived Vulnerability to Disease Questionnaire (PVD) is the most extensively used measure when it comes to assessing subjective vulnerability to infectious diseases. However, this measure is not yet accessible to the Portuguese population. The present study aimed to adapt and validate the PVD with 136 Portuguese participants. METHODS: Factorial, convergent and discriminant validity (of both the scale and between each factor), and reliability analysis were assessed. RESULTS: A modified bifactorial model, comprised of Perceived Infectability and Germ Aversion factors, was obtained, with acceptable goodness-of-fit indices, adequate convergent and discriminant validity, and good internal consistencies. CONCLUSIONS: Overall, the 10-items European-Portuguese PVD appears to be a reliable and valid measure of one's perceived vulnerability to disease, with potential relevance for application in both research and clinical practice pertaining to disease-avoidance processes.

Evolution of Acridines and Xanthenes as a Core Structure for the Development of Antileishmanial Agents.

Nowadays, leishmaniasis constitutes a public health issue in more than 88 countries, affecting mainly people from the tropics, subtropics, and the Mediterranean area. Every year, the prevalence of this infectious disease increases, with the appearance of 1.5-2 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis, endangering approximately 350 million people worldwide. Therefore, the absence of a vaccine or effective treatment makes the discovery and development of new antileishmanial therapies one of the focuses for the scientific community that, in association with WHO, hopes to eradicate this disease shortly. This paper is intended to highlight the relevance of nitrogen- and oxygen-containing tricyclic heterocycles, particularly acridine and xanthene derivatives, for the development of treatments against leishmaniasis. Thus, in this review, a thorough compilation of the most promising antileishmanial acridine and xanthene derivatives is performed from both natural and synthetic origins. Additionally, some structure-activity relationship studies are also depicted and discussed to provide insight into the optimal structural features responsible for these compounds' antileishmanial activity.

The Portuguese Third Version of the Copenhagen Psychosocial Questionnaire: Preliminary Validation Studies of the Middle Version among Municipal and Healthcare Workers.

A third version of the Copenhagen Psychosocial Questionnaire (COPSOQ III) was developed internationally aiming to respond to new trends in working conditions, theoretical concepts, and international experience. This article aims to present the preliminary validation studies for the Portuguese middle version of COPSOQ III. This is an exploratory cross-sectional study viewing the cross-cultural adaption of COPSOQ III to Portugal, ensuring the contents and face validity and performing field-testing in order to reduce the number of items and to obtain insight into the data structure, through classic test theory and item response theory approaches. The qualitative study encompassed 29 participants and the quantitative one 659 participants from municipalities and healthcare settings. Content analysis suggested that minor re-wording could improve the face validity of items, while a reduced version, with 85 items, shows psychometric stability, achieving good internal consistency in all subscales. The COPSOQ III Portuguese middle version proved to be a valid preliminary version for future validation studies with various populations, able to be used in correlational studies with other dimensions.

The role of fear in the relationship between vicarious violence at work and work ability in nurses: A cross-sectional study.

Fear is a powerful emotion that can influence future behavior. This study investigated how fear influences the relationship between vicarious violence at work and employees' work ability. This is a quantitative cross-sectional study. Self-report data were collected from 154 Portuguese nurses who completed an online survey. Statistical significance of the indirect effect was based on bias-corrected bootstrap confidence intervals. The results support the mediation model. Those who observe/hear of others being beaten or threatened experience strong affective reactions, such as fear, which in turn has a negative impact on the assessment of their work ability. We suggest that occupational safety and health programs designed to prevent violence at work take into account those who experience violence at work vicariously and include strategies and interventions focused on affective reactions to minimize the negative effects of vicarious violence at work, with benefits in employees' improved ability to work.

The Interplay between Chronotype and Emotion Regulation in the Recognition of Facial Expressions of Emotion.

Emotion regulation strategies affect the experience and processing of emotions and emotional stimuli. Chronotype has also been shown to influence the processing of emotional stimuli, with late chronotypes showing a bias towards better processing of negative stimuli. Additionally, greater eveningness has been associated with increased difficulties in emotion regulation and preferential use of expressive suppression strategies. Therefore, the present study aimed to understand the interplay between chronotype and emotion regulation on the recognition of dynamic facial expressions of emotion. To that end, 287 participants answered self-report measures and performed an online facial emotion recognition task from short video clips where a neutral face gradually morphed into a full-emotion expression (one of the six basic emotions). Participants should press the spacebar to stop each video as soon as they could recognize the emotional expression, and then identify it from six provided labels/emotions. Greater eveningness was associated with shorter response times (RT) in the identification of sadness, disgust and happiness. Higher scores of expressive suppression were associated with longer RT in identifying sadness, disgust, anger and surprise. Expressive suppression significantly moderated the relationship between chronotype and the recognition of sadness and anger, with chronotype being a significant predictor of emotion recognition times only at higher levels of expressive suppression. No significant effects were observed for cognitive reappraisal. These results are consistent with a negative bias in emotion processing in late chronotypes and increased difficulty in anger and sadness recognition for expressive suppressor morning-types.

Impact of Psychological Aggression at the Workplace on Employees' Health: A Systematic Review of Personal Outcomes and Prevention Strategies.

Psychological aggression perpetrated by customers, coworkers, and supervisors is a behavior frequently experienced in the workplace with negative consequences for an individual's health. The aim of this systematic review was to examine the personal outcomes of overt workplace psychological aggression and summarize empirical evidence on how to prevent and reduce its effects. A search on PubMed, Scopus, ProQuest, and Web of Science electronic databases was made. Data were obtained from 30 studies (26 cross-sectional, 3 longitudinal, 1 quasi-experimental) representing 20,683 employees. Longitudinal studies indicated that workplace psychological aggression is significantly associated with musculoskeletal injury and psychological strains (anxiety, depression, anger) over time. Research also suggests that psychological aggression at work predicts fear, emotional exhaustion, depersonalization, personal accomplishment, and physical symptoms, for example. Additionally, the information collected suggested that support from coworkers, supervisors, and management; informational support; political skills; job resources; and confidence to prevent and respond to aggression moderate significantly the impact of workplace psychological aggression on personal and organizational outcomes. Perceptions of a violence-prevention climate, aggression-preventive supervisor behavior, and aggression-preventive employee effort are also significantly associated with a reduction in psychological aggression at work and strains. In conclusion, this review allows us to understand the effects of the psychological aggression by identifying the preventive strategies that could be adopted by managers, supervisors, or leaders to deal with it and promote individual's health in the workplace.

COVID-19 in Portugal: exploring the immediate psychological impact on the general population.

Like previous pandemics, the coronavirus disease 2019 (COVID-19) has direct and indirect effects, including in mental health. To evaluate the immediate psychological impact of COVID-19, we conducted an online survey in Portugal (24-27 March 2020), using the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21). From the 10,529 participants (M = 31.33; SD = 9.73), 83.4% were women, had a mean age of 31.2 years, and 70.9% were active workers. Depression, anxiety, and stress were rated as moderate to severe in 11.7%, 16.9%, and 5.6% of the sample, respectively. Moreover, 49.2% of participants reported a moderate or severe psychological impact of the outbreak. Women, the unemployed, those with lower education, living in rural areas, and with flu-like symptoms or chronic disorders were risk factors. Further research is needed to identify vulnerable groups to better inform and adapt mental health policies and interventions.

Portuguese Version of the 12-Item Violence Prevention Climate Scale: Test of Psychometric Properties.

BACKGROUND AND PURPOSE: A violence prevention climate is critical for nurses' well-being but also for nursing practice and the quality of care. This study examined the reliability and factor validity of the European Portuguese version of the 12-item Violence Prevention Climate Scale (VPCS). METHODS: Data came from a sample of 120 nurses providing care in Portugal. Confirmatory factor analysis was used to test the structural theory of the scale. RESULTS: First and second-order confirmatory factor analysis models showed identical goodness-of-fit suggesting the adequacy of the models to the sample data. Our results also provide evidence of composite reliability, and convergent and discriminant validity. CONCLUSIONS: Consistent with previous studies, data from this study showed that the Portuguese version of the 12-item VPCS is a reliable and valid scale to evaluate nurses' perceptions of a violence prevention climate.

Job Stress, Burnout and Coping in Police Officers: Relationships and Psychometric Properties of the Organizational Police Stress Questionnaire.

Policing is a stressful occupation, which impairs police officers' physical/mental health and elicits burnout, aggressive behaviors and suicide. Resilience and coping facilitate the management of job stress policing, which can be operational or organizational. All these constructs are associated, and they must be assessed by instruments sensitive to policing idiosyncrasies. This study aims to identify operational and organizational stress, burnout, resilient coping and coping strategies among police officers, as well to analyze the psychometric properties of a Portuguese version of the Organizational Police Stress Questionnaire. A cross-sectional study, with online questionnaires, collected data of 1131 police officers. With principal components and confirmatory factor analysis, PSQ-org revealed adequate psychometric properties, despite the exclusion of four items, and revealed a structure with two factors (poor management and lack of resources, and responsibilities and burden). Considering cut-off points, 88.4% police officers presented high operational stress, 87.2% high organizational stress, 10.9% critical values for burnout and 53.8% low resilient coping, preferring task-orientated than emotion and avoidance coping. Some differences were found according to gender, age and job experience. Job stress and burnout correlated negatively with resilient coping, enthusiasm towards job and task-orientated coping. Results reinforce the importance to invest on police officers' occupational health.

Evolution of chromone-like compounds as potential antileishmanial agents, through the 21st century.

INTRODUCTION: Leishmaniasis is one of the most neglected diseases of modern times that mainly affects people from developing countries, with approximately 350 million people considered at risk of developing leishmaniasis. Therefore, the development of novel antileishmanial treatments is becoming the focus of numerous research groups, with the support of the World Health Organization, which hopes to eradicate this disease in the near future. AREAS COVERED: This review focuses on the interest of chromones for the development of future treatments against leishmaniasis. In addition to plant-based chromone derivatives, structure-activity relationship studies that aim to identify the optimal structural features of the chromones' antileishmanial activity are also described and discussed. EXPERT OPINION: The numerous examples of chromones depicted in this paper, allied with the SAR studies presented herein, suggest that the chromone scaffold is a privileged core for the design and development of novel antileishmanial agents. However, some concerns have been raised concerning the considerable variability observed in the results throughout the scientific bibliography. These inconsistencies may explain the absence of pharmacodynamic and pharmacokinetic studies as well as clinical trials.

Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages.

Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R2 = 0.78, R2 = 0.71, and R2 = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients' outcome.

Ethnic influences on the perceptual properties of human chemosignals.

Individuals of African and Caucasian descent show different chemical signatures in their body odors (BO). Does such biological difference have a perceptual correlate? We tested BO donors and raters of Afro-Portuguese (AP) and Caucasian (C) descent to investigate whether olfactory ratings reveal an ethnic bias and whether olfactory ethnic discrimination is possible. C (vs. AP) women rated the C BO as more pleasant, even when controlling for intensity. The C BO labelled as AP was rated as more intense by C raters. Although discriminability of ethnicity and sex is at chance, a nominal advantage for AP vs. C BO emerges.

Factorial Structure of the Morningness-Eveningness-Stability-Scale (MESSi) and Sex and Age Invariance.

Assessing morningness-eveningness preferences (chronotype), an individual characteristic that is mirrored in daily mental and physiological fluctuations, is crucial given their overarching influence in a variety of domains. The current work aimed to investigate the best factor structure of an instrument recently presented to asses this characteristic: the Morningness-Eveningness-Stability-Scale improved (MESSi). For the first time, the originally proposed three-factor structure was pitched against a uni- and a two-factor solution. Another novelty was to establish that the best-fitting model would be invariant in relation to sex and age, two variables that influence chronotype. A Confirmatory Factor Analyses on the data obtained from a sample of 2096 German adults (age: 18-76; M = 25.5, SD = 7.64) revealed that the originally proposed three-factor structure of the MESSi - Morning Affect, Eveningness, and Distinctness - was the only one to achieve acceptable fit indicators. Furthermore, each scale obtained good internal consistency. In order to assess age invariance, following the literature on development and chronotype, our sample was divided into three age groups: 18-21 years, 22-31 years, and 32 years or older. Full measurement invariance of the three-factor model was found for sex and age. Regarding differences between sexes, females did not differ significantly from males in Morning Affect, but scored significantly lower on Eveningness and higher on Distinctness; this last result has been consistent across validation studies of the MESSi. With respect to age differences, the oldest group scored lower on Eveningness and Distinctness in comparison with the other two age-groups; the intermediate group (age: 22-31) scored lower on Morning Affect when compared to both the younger and older age groups. Additionally, both Eveningness and Distinctness were negatively correlated with age. This latter relation has been consistently reported in other validation studies. Our results reinforce the idea that the MESSi assesses three different components of chronotype in a reliable manner and that this instrument can be used to explore sex and age differences.