Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours

Assessing brain immune activation in psychiatric disorders:Clinical and preclinical PET imaging studies of the 18-kDa translocator protein

Accumulating evidence from different lines of research suggests an involvement of the immune system in the pathophysiology of several psychiatric disorders. During recent years, a series of positron emission tomography (PET) studies have been published using radioligands for the translocator protein (TSPO) to study microglia activation in schizophrenia, bipolar I disorder, major depression, autism spectrum disorder, and drug abuse. The results have been somewhat conflicting, which could be due to differences both in patient sample characteristics and in PET methods. In particular, further work is needed to address both methodological and biological sources of variability in TSPO levels, a process in which the use of animal models and small animal PET systems can be a valuable tool. Given this development, PET studies of immune activation have the potential to further increase our understanding of disease mechanisms in psychiatric disorders, which is a requisite in the search for new treatment approaches. Furthermore, molecular imaging could become an important clinical tool for identifying specific subgroups of patients or disease stages that would benefit from treatment targeting the immune system

The pivotal role of clinical ethics consults in critical clinical decision making in the Neonatal Intensive Care Unit within an Arab culture

Medical Ethics is a relatively new field in developing countries and, to date, Lebanon is the only Arab country that offers bedside ethics consults; however, this is limited to a single medical center, the American University of Beirut Medical Center (AUBMC). The clinical ethicist running the bedside clinical ethics service was trained in the United States and the United Kingdom. However, once she began practicing in Lebanon, she realized that much of what she learned in terms of theory and practice as well as navigating ethical issues did not apply to the local context. Rather, much needed to be sifted and adapted to a different culture, social decorum, and mentality. This is more evident when working with patients in the Neonatal Intensive Care Unit (NICU), where parents coming from various areas in the region bring in their unique values and beliefs. The admission of a premature newborn to the NICU is often a strenuous experience for parents and a challenge for healthcare providers. Ethical conundrums often arise when there is a potential partial success with a plan of treatment(s). For example, from an ethical point of view resuscitation is less problematic than surviving severe illness with brain damage, and thus controversial issues linked to quality of life surface as living in a vegetative or incapacitated state can be deemed worse than death. In this article, we present our own experience as neonatologists and clinical ethics consultant (CEC) teaming up at the AUBMC’s NICU in an attempt at navigating the muddy waters of decision-making and ethical controversies within an Arab culture characterized with specificities that are often neglected and thus might negatively impact the decision regarding the right plan of treatment. The aim is trying to come up with a recommendation that is in the best interest of the infant and his/her parents and in an attempt to ensure that parents understand the importance of them being part of the decision-making process

Requirements Engineering, Software Testing and Education: A Systematic Mapping

The activities of requirements engineering and software testing are intrinsically related to each other, as these two areas are linked when seeking to specify and also ensure the expectations of a software product, with quality and on time. This systematic mapping study aims to verify how requirements and testing are being addressed together in the educational context.Comment: 20 pages, in Portuguese languag

Caracterização de óbitos de recém-nascidos no Brasil: revisão integrativa

Introduction: The investigation of newborn deaths aims to evaluate the link between it and the quality of care received during prenatal care, delivery and birth, in order to contribute to control measures. In this context, the objective was to identify variables related to obstetric and / or neonatal data associated with death of newborns. Method: This is an integrative literature review, which used 11 articles from the Medical Literature Analysis and Latin American and Caribbean Literature in Health Sciences databases, published in Portuguese between 2014 and 2018, and should be linked to the theme proposed. Development: The results indicate that the causes of neonatal deaths are associated with maternal characteristics (age, education, type of gestation and delivery), neonatal (birth weight, gestational age, apgar and sex) and inadequacy of pre- natal, delivery and follow-up of the newborn. Conclusion: The survey of these variables at the national level guide interventionist measures for the reduction of infant mortality. &nbsp;Introdução: A investigação sobre óbitos de recém-nascidos tem por finalidade avaliar a ligação do mesmo com a qualidade da assistência recebida no pré-natal, parto e nascimento, visando contribuir com medidas de controle. Nesse contexto, objetivou-se identificar as variáveis relativas aos dados obstétricos e/ou neonatais associados ao óbito de recém-nascidos de estudos realizados no Brasil. Métodos: Trata-se de uma revisão integrativa de literatura, que utilizou 11 artigos das bases de dados Medical Literature Analysis e Literatura Latino-Americana e do Caribe em Ciências da Saúde, publicados em português entre os anos de 2014 a 2018, devendo estar ligados ao tema proposto. Desenvolvimento: Os resultados apontam que as causas dos óbitos neonatais associamse as características maternas (idade, escolaridade, tipo de gestação e parto), neonatais (peso ao nascer, idade gestacional, apgar e sexo) e inadequação dos cuidados prestados no pré-natal, parto e acompanhamento do recém-nascido. Conclusão: O levantamento dessas variáveis a nível nacional norteiam medidas intervencionistas para a redução da mortalidade infantil

Another Look at Pyrroloiminoquinone Alkaloids-Perspectives on Their Therapeutic Potential from Known Structures and Semisynthetic Analogues

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS² runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid carcinoma (PANC-1) cell line IC50 data was obtained for 16 compounds and two therapeutic standards. These results along with data gleaned from the literature provided useful structure activity relationship conclusions. Three structural motifs proved to be important in maximizing potency against PANC-1: (i) conjugation within the core of the ABC-ring; (ii) the presence of a positive charge in the C-ring; and (iii) inclusion of a 4-ethyl phenol or 4-ethyl phenol acetate substituent off the B-ring. Two compounds, makaluvamine J (9) and 15-O-acetyl makaluvamine J (15), contained all three of these frameworks and exhibited the best potency with IC50 values of 54 nM and 81 nM, respectively. These two most potent analogs were then tested against the OVCAR-5 cell line and the presence of the acetyl group increased the potency 14-fold from that of 9 whose IC50 = 120 nM vs. that of 15 having IC50 = 8.6 nM

Age and sex‐related variability in the presentation of generalized anxiety and depression symptoms

Background: Generalized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity. Method: We conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD‐7) and Patient Health Questionnaire (PHQ‐9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16–93 years). We assessed age‐ and sex‐related variability in latent factors and individual symptoms using multiple logistic regression. Results: Four factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker–Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p &lt; .001) and females to report somatic symptoms (p &lt; .001). Conclusion: Significant age and sex variability suggest that classic diagnostic criteria reflect the presentation most commonly seen in younger males. This study provides avenues for diagnostic adaptation and factor‐specific interventions

Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity

Background: Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety. Methods: We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test. Results: In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05). Limitations: The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires. Conclusions: Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder

Prospective longitudinal associations between persistent sleep problems in childhood and anxiety and depression disorders in adulthood

The objective of this study was to examine the associations between persistent childhood sleep problems and adulthood anxiety and depression. Parents of 943 children (52% male) participating in the Dunedin Multidisciplinary Health and Development Study provided information on their children’s sleep and internalizing problems at ages 5, 7, and 9 years. When the participants were 21 and 26 years, adult anxiety and depression were diagnosed using a standardized diagnostic interview. After controlling for childhood internalizing problems, sex, and socioeconomic status, persistent sleep problems in childhood predicted adulthood anxiety disorders (OR (95% CI) = 1.60 (1.05– 2.45), p = .030) but not depressive disorders (OR (95% CI) = .99 (.63–1.56), p = .959). Persistent sleep problems in childhood may be an early risk indicator of anxiety in adulthood