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OBJECTIVE: Experiences of child maltreatment are associated with cardiovascular risk and disease in adulthood; however, the mechanisms underlying these associations are poorly understood. METHODS: We examined associations between retrospectively self-reported exposure to child maltreatment (Early Trauma Inventory Self-Report Short Form) and inflammatory responses to mental stress among adults (mean age = 50 years) who recently had a myocardial infarction ( n = 227). Inflammation was assessed as blood interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 concentrations, measured before and after a standardized public speaking stress task. We used mixed linear regression models adjusting for cardiovascular disease severity, medication usage, and psychosocial, demographic, and life-style factors. RESULTS: In women, increases in IL-6 levels and MMP-9 levels with stress were smaller in those exposed to sexual abuse, relative to those unexposed (IL-6 geometric mean increases = 1.6 [95% confidence interval {CI} = 1.4-1.9] pg/ml versus 2.1 [95% CI = 1.8-2.4] pg/ml; MMP-9 geometric mean increases = 1.0 [95% CI = 0.9-1.2] ng/ml versus 1.2 [95% CI = 1.1-1.4] ng/ml). No differences were noted for emotional or physical abuse. By contrast in men, individuals exposed to sexual abuse had larger IL-6 responses than those not exposed to abuse. CONCLUSIONS: These findings suggest sex differences in stress response among survivors of a myocardial infarction exposed to abuse early in life. They also underscore the importance of examining sex as an effect modifier of relationships between exposure to early life adversity and inflammatory responses to mental stressors in midlife.
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Maus-Tratos Infantis , Infarto do Miocárdio , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metaloproteinase 9 da Matriz , Interleucina-6 , Estudos Retrospectivos , Maus-Tratos Infantis/psicologia , Infarto do Miocárdio/epidemiologiaRESUMO
Early life stress (ELS) has been associated with an increased risk of cardiovascular disease. We examined whether ELS was associated with autonomic function and stress reactivity among individuals with coronary heart disease (CHD). We included patients with stable CHD from two parallel studies, the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2), and assessed ELS using the Early Trauma Inventory-Self-Report-Short Form. Participants underwent a laboratory-based mental stress task while undergoing ambulatory electrocardiographic monitoring. We used multivariate linear regression models to estimate the associations between ELS and heart rate variability (HRV; low frequency [LF], high frequency [HF], and LF and HF [LH] ratio). The analytic sample included 405 MIPS and 284 MIMS2 participants. Most participants endorsed at least one experience of ELS (92.2%). Although we did not observe associations between ELS and HRV outcomes in the overall sample, ELS was associated with lower LH ratio HRV during recovery in the posttraumatic stress disorder (PTSD) subgroup, ELS x PTSD interaction, p = .041. In the MIMS2 subgroup, ELS was associated with lower resting period LF HRV, B Ì $ \widehat{B} $ = -0.16 ln ms2 ; 95% CI [-0.31, -0.02]. Exposure to physical trauma was associated with decreased HF HRV overall reactivity only among participants with high to moderate depressive symptoms, B Ì $ \widehat{B} $ = -0.52 ln ms2 vs. B Ì $ \widehat{B} $ = 0.01 ln ms2 , p = .013. Overall, heterogeneous associations between ELS and HRV emerged, suggesting the need for additional research regarding longer-term ambulatory HRV.
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Experiências Adversas da Infância , Doença das Coronárias , Transtornos de Estresse Pós-Traumáticos , Sistema Nervoso Autônomo , Frequência Cardíaca/fisiologia , HumanosRESUMO
OBJECTIVE: Posttraumatic stress disorder (PTSD) is a disabling condition affecting a large segment of the population; however, current treatment options have limitations. New interventions that target the neurobiological alterations underlying symptoms of PTSD could be highly beneficial. Transcutaneous cervical (neck) vagal nerve stimulation (tcVNS) has the potential to represent such an intervention. The goal of this study was to determine the effects of tcVNS on neural responses to reminders of traumatic stress in PTSD. METHODS: Twenty-two participants were randomized to receive either sham (n = 11) or active (n = 11) tcVNS stimulation in conjunction with exposure to neutral and personalized traumatic stress scripts with high-resolution positron emission tomography scanning with radiolabeled water for brain blood flow measurements. RESULTS: Compared with sham, tcVNS increased brain activations during trauma scripts (p < .005) within the bilateral frontal and temporal lobes, left hippocampus, posterior cingulate, and anterior cingulate (dorsal and pregenual), and right postcentral gyrus. Greater deactivations (p < .005) with tcVNS were observed within the bilateral frontal and parietal lobes and left thalamus. Compared with tcVNS, sham elicited greater activations (p < .005) in the bilateral frontal lobe, left precentral gyrus, precuneus, and thalamus, and right temporal and parietal lobes, hippocampus, insula, and posterior cingulate. Greater (p < .005) deactivations were observed with sham in the right temporal lobe, posterior cingulate, hippocampus, left anterior cingulate, and bilateral cerebellum. CONCLUSIONS: tcVNS increased anterior cingulate and hippocampus activation during trauma scripts, potentially indicating a reversal of neurobiological changes with PTSD consistent with improved autonomic control.Trial Registration: No. NCT02992899.
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Transtornos de Estresse Pós-Traumáticos , Estimulação do Nervo Vago , Encéfalo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/terapia , Estimulação do Nervo Vago/métodosRESUMO
Da Costa originally described Soldier's Heart in the 19th Century as a syndrome that occurred on the battlefield in soldiers of the American Civil War. Soldier's Heart involved symptoms similar to modern day posttraumatic stress disorder (PTSD) as well as exaggerated cardiovascular reactivity felt to be related to an abnormality of the heart. Interventions were appropriately focused on the cardiovascular system. With the advent of modern psychoanalysis, psychiatric symptoms became divorced from the body and were relegated to the unconscious. Later, the physiology of PTSD and other psychiatric disorders was conceived as solely residing in the brain. More recently, advances in psychosomatic medicine led to the recognition of mind-body relationships and the involvement of multiple physiological systems in the etiology of disorders, including stress, depression PTSD, and cardiovascular disease, has moved to the fore, and has renewed interest in the validity of the original model of the Soldier's Heart syndrome.
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Guerra Civil Norte-Americana , Doenças Cardiovasculares/história , Militares/história , Transtornos de Estresse Pós-Traumáticos/história , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/psicologia , História do Século XIX , Humanos , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados UnidosRESUMO
The colors that people see depend not only on the surface properties of objects but also on how these properties interact with light as well as on how light reflected from objects interacts with an individual's visual system. Because individual visual systems vary, the same visual stimulus may elicit different perceptions from different individuals. #thedress phenomenon drove home this point: different individuals viewed the same image and reported it to be widely different colors: blue and black versus white and gold. This phenomenon inspired a collection of demonstrations presented at the Vision Sciences Society 2015 Meeting which showed how spatial and temporal manipulations of light spectra affect people's perceptions of material colors and illustrated the variability in individual color perception. The demonstrations also explored the effects of temporal alterations in metameric lights, including Maxwell's Spot, an entoptic phenomenon. Crucially, the demonstrations established that #thedress phenomenon occurs not only for images of the dress but also for the real dress under real light sources of different spectral composition and spatial configurations.
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Percepção de Cores , Visão Intraocular , Cor , Humanos , Luz , IluminaçãoRESUMO
BACKGROUND: The direction of the association between inflammation and depressive symptoms remains inconsistent. The objective of this study was to evaluate the temporal relationship between inflammation and depressive symptoms, and to assess the role of genetic factors on this association. METHODS: In this longitudinal cross-lagged twin difference study, we examined 166 (83 pairs) middle-aged male twins recruited from the Vietnam Era Twin Registry, who were assessed at baseline and after 7â¯years of follow-up. We assayed plasma levels of two inflammatory biomarkers, interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP) and measured depressive symptoms using the Beck Depression Inventory-II (BDI). To evaluate the direction of the association, we constructed multivariable mixed-effects regression models and calculated standardized beta-coefficients to compare the strength of the within-pair association for both pathways. We then conducted a stratified analysis by zygosity and assessed the associations in monozygotic and dizygotic twin pairs separately. RESULTS: The 166 twins were 95% white and had a mean (SD) age of 54 (3) years at baseline. The cross-lagged analysis showed significant and positive associations from visit 1 IL-6 to visit 2 BDI across all models (beta-coefficients ranging from 0.18 to 0.22). However, the opposite pathway (visit 1 BDI to visit 2 IL-6) was not significant after adjusting for confounding factors. In contrast, visit 1 BDI was significantly associated with visit 2 CRP in all models (beta-coefficients ranging from 0.23 to 0.33), while the opposite pathway (visit 1 CRP to visit 2 BDI) showed no significant association. When stratifying by zygosity, significant associations from IL-6 to depression were only seen in monozygotic twins, but associations from depression to CRP were more robust in dizygotic twins, which implies that genetic factors may play a role in this association. CONCLUSIONS: The association between inflammation and depression may be bidirectional. Elevated IL-6 levels are more likely to be a risk factor of depression rather than a consequence, while the opposite may be true for elevated CRP. The biological underpinnings of these bidirectional pathways need further evaluation.
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Depressão/complicações , Depressão/imunologia , Inflamação/fisiopatologia , Biomarcadores , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Depressão/fisiopatologia , Transtorno Depressivo/complicações , Transtorno Depressivo/imunologia , Humanos , Inflamação/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-6/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , Gêmeos Dizigóticos , Gêmeos Monozigóticos , VeteranosRESUMO
BACKGROUND: This study aims to determine reported prevalence of hypertensive disorders in pregnancy (HDP) and maternal and neonatal outcomes associated with these disorders among women delivering at selected hospitals across Haiti. METHODS: A retrospective review of 8822 singleton deliveries between January 2012 and December 2014 was conducted at four hospitals in separate Departments across Haiti. Researchers examined the proportion of women with reported HDP (hypertension, preeclampsia, eclampsia) and the association between women with HDP and three neonatal outcomes: low birth weight, preterm birth, and stillbirths; and two maternal outcomes: placental abruption and maternal death in Hôpital Albert Schweitzer (HAS). Odds ratios for associations between HDP and perinatal outcomes at HAS were assessed using logistic regression, adjusting for potential confounders. RESULTS: Of the 8822 singleton births included in the study, 510 (5.8%) had a reported HDP (including 285 (55.9%) preeclampsia, 119 (23.3%) eclampsia, and 106 (20.8%) hypertension). Prevalence of HDP among each hospital was: HAS (13.5%), Hôpital Immaculée Conception des Cayes (HIC) (3.2%), Fort Liberté (4.3%), and Hôpital Sacré Coeur de Milot (HSC) (3.0%). Among women at HAS with HDP, the adjusted odds of having a low birth weight baby was four times that of women without HDP (aOR 4.17, 95% CI 3.19-5.45), more than three times that for stillbirths (aOR 3.51, 95% CI 2.43-5.06), and five times as likely to result in maternal death (aOR 5.13, 95% CI 1.53-17.25). Among the three types of HDP, eclampsia was associated with the greatest odds of adverse events with five times the odds of having a low birth weight baby (aOR 5.00, 95% CI 2.84-8.79), six times the odds for stillbirths (aOR 6.34, 95% CI 3.40-11.82), and more than twelve times as likely to result in maternal death (aOR 12.70, 95% CI 2.33-69.31). CONCLUSIONS: A high prevalence of HDP was found among a cohort of Haitian mothers. HDP was associated with higher rates of adverse maternal and neonatal outcomes in HAS, which is comparable to studies of HDP conducted in high-income countries.
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Descolamento Prematuro da Placenta/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido de Baixo Peso , Nascimento Prematuro/epidemiologia , Natimorto/epidemiologia , Adulto , Estudos de Casos e Controles , Coleta de Dados , Feminino , Haiti/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Hipertensão Induzida pela Gravidez/mortalidade , Mortalidade Materna , Vigilância da População , Gravidez , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.
Assuntos
Reflexo de Sobressalto/imunologia , Meio Social , Toxoplasma/imunologia , Toxoplasmose/imunologia , População Urbana , Estimulação Acústica , Adulto , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We describe an efficient and convergent synthesis of a series of (1'S,2R,4'S)-3H-4'-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes] displaying potency for the α7 nicotinic acetylcholine receptor (nAChR) and good selectivity vs. the related 5-HT3A receptor.
Assuntos
Compostos Bicíclicos com Pontes/metabolismo , Desenho de Fármacos , Octanos/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Cristalografia por Raios X , Humanos , Ligação de Hidrogênio , Conformação Molecular , Agonistas Nicotínicos/química , Agonistas Nicotínicos/metabolismo , Octanos/síntese química , Octanos/química , Ligação Proteica , Receptores 5-HT3 de Serotonina/química , Receptores 5-HT3 de Serotonina/metabolismo , Estereoisomerismo , Receptor Nicotínico de Acetilcolina alfa7/químicaRESUMO
Triazolopyridine ethers with mGlu2 positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mGlu2 PAMs for the treatment of schizophrenia and merit further preclinical investigation.
Assuntos
Éteres/farmacologia , Piridinas/farmacologia , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Esquizofrenia/tratamento farmacológico , Triazóis/farmacologia , Administração Oral , Regulação Alostérica/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Éteres/administração & dosagem , Éteres/química , Haplorrinos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular , Piridinas/administração & dosagem , Piridinas/química , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/metabolismo , Esquizofrenia/metabolismo , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/químicaRESUMO
Following publication of the original article [1], the authors pointed out that the Methods included one step that is no longer necessary but which was inadvertently carried over from an earlier protocol.
RESUMO
BACKGROUND: Adverse birth and neonatal outcomes disproportionately affect African American women and infants compared to those of other races/ethnicities. While significant research has sought to identify underlying factors contributing to these disparities, current understanding remains limited, constraining prevention, early diagnosis, and treatment. With the development of next generation sequencing techniques, the contribution of the vaginal microbiome to adverse maternal and neonatal outcomes has come under consideration. However, most microbiome in pregnancy studies include few African American women, do not consider the potential contribution of non-vaginal microbiome sites, and do not consider the effects of sociodemographic or behavioral factors on the microbiome. METHODS: We conceived our on-going, 5-year longitudinal study, Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women, as an intra-race study to enable the investigation of risk and protective factors within the disparate group. We aim to recruit over 500 pregnant African American women, enrolling them into the study at 8-14 weeks of pregnancy. Participants will be asked to complete questionnaires and provide oral, vaginal, and gut microbiome samples at enrollment and again at 24-30 weeks. Chart review will be used to identify pregnancy outcomes, infections, treatments, and complications. DNA will be extracted from the microbiome samples and sequencing of the V3 and V4 regions of the 16S rRNA gene will be conducted. Processing and mapping will be completed with QIIME and operational taxonomic units (OTUs) will be mapped to Greengenes version 13_8. Community state types (CSTs) and diversity measures at each site and time will be identified and considered in light of demographic, psychosocial, clinical, and biobehavioral variables. DISCUSSION: This rich data set will allow future consideration of risk and protective factors, between and within groups of women, providing the opportunity to uncover the roots of the persistent health disparity experienced by African American families.
Assuntos
Negro ou Afro-Americano , Protocolos Clínicos , Microbioma Gastrointestinal , Boca/microbiologia , Nascimento Prematuro/microbiologia , Vagina/microbiologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Gravidez , Resultado da Gravidez , RNA Ribossômico 16S/genéticaRESUMO
Retrospective reports of exposure to childhood trauma indicate it is common. There is growing interest in relationships between maternal exposure to childhood adversity, perinatal mental health, and pregnancy outcomes. The goal of this study was to describe the self-reported prevalence and test-retest reliability of exposure to childhood maltreatment using the Childhood Trauma Questionnaire among adult women around the time of pregnancy. A substantial proportion of women reported exposure to maltreatment and reliability was generally at least moderate, indicating consistent reporting.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Maus-Tratos Infantis/psicologia , Inquéritos e Questionários/normas , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Feminino , Humanos , Gravidez , Prevalência , Escalas de Graduação Psiquiátrica/normas , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos Retrospectivos , AutorrelatoRESUMO
Characterizing humans' ability to discriminate changes in illumination provides information about the visual system's representation of the distal stimulus. We have previously shown that humans are able to discriminate illumination changes and that sensitivity to such changes depends on their chromatic direction. Probing illumination discrimination further would be facilitated by the use of computer-graphics simulations, which would, in practice, enable a wider range of stimulus manipulations. There is no a priori guarantee, however, that results obtained with simulated scenes generalize to real illuminated scenes. To investigate this question, we measured illumination discrimination in real and simulated scenes that were well-matched in mean chromaticity and scene geometry. Illumination discrimination thresholds were essentially identical for the two stimulus types. As in our previous work, these thresholds varied with illumination change direction. We exploited the flexibility offered by the use of graphics simulations to investigate whether the differences across direction are preserved when the surfaces in the scene are varied. We show that varying the scene's surface ensemble in a manner that also changes mean scene chromaticity modulates the relative sensitivity to illumination changes along different chromatic directions. Thus, any characterization of sensitivity to changes in illumination must be defined relative to the set of surfaces in the scene.
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Percepção de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Iluminação , Adulto , Gráficos por Computador , Simulação por Computador , Feminino , Humanos , Masculino , Adulto JovemRESUMO
22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months, whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p < 0.05), Speech (p < 0.01), and Symbolic domains (p < 0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes.
Assuntos
Síndrome da Deleção 22q11 , Cálcio/sangue , Hipocalcemia , Transtornos do Neurodesenvolvimento , Habilidades Sociais , Síndrome da Deleção 22q11/sangue , Síndrome da Deleção 22q11/fisiopatologia , Adolescente , Adulto , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Transtornos da Comunicação/sangue , Transtornos da Comunicação/fisiopatologia , Feminino , Humanos , Hipocalcemia/sangue , Hipocalcemia/fisiopatologia , Lactente , Estudos Longitudinais , Masculino , Transtornos do Neurodesenvolvimento/sangue , Transtornos do Neurodesenvolvimento/fisiopatologia , Adulto JovemRESUMO
Solid state lighting is becoming a popular light source for color vision experiments. One of the advantages of light emitting diodes (LEDs) is the possibility to shape the target light spectrum according to the experimenter's needs. In this paper, we present a method for creating metameric lights with an LED-based spectrally tunable illuminator. The equipment we use consists of six Gamma Scientific RS-5B lamps, each containing nine different LEDs and a 1 m integrating sphere. We provide a method for describing the (almost) entire set of illuminant metamers. It will be shown that the main difficulty in describing this set arises as the result of the intensity dependent peak-wavelength shift, which is manifested by the majority of the LEDs used by the illuminators of this type. We define the normalized metamer set describing all illuminator spectra that colorimetrically match a given chromaticity. Finally, we describe a method for choosing the smoothest or least smooth metamer from the entire set.
Assuntos
Cor , Iluminação/instrumentação , Modelos Teóricos , Refratometria/instrumentação , Semicondutores , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de RadiaçãoRESUMO
Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers. Support for this unique mechanism is provided by site-directed mutagenesis studies, biophysical characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal structure of an NP dimer of trimers (or hexamer) comprising three NP_A:NP_B dimeric subunits. Each NP_A:NP_B dimeric subunit contains two ligands that bridge two composite, protein-spanning binding sites in an antiparallel orientation to form a stable quaternary complex. Optimization of the initial screening hit produced an analog that protects mice from influenza-induced weight loss and mortality by reducing viral titers to undetectable levels throughout the course of treatment.
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Antivirais/farmacologia , Nucleoproteínas/química , Nucleoproteínas/metabolismo , Orthomyxoviridae/fisiologia , Bibliotecas de Moléculas Pequenas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/uso terapêutico , Cristalografia por Raios X , Modelos Animais de Doenças , Ensaios de Triagem em Larga Escala , Hidrodinâmica , Camundongos , Modelos Moleculares , Nucleoproteínas/ultraestrutura , Orthomyxoviridae/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Bibliotecas de Moléculas Pequenas/uso terapêutico , SoluçõesRESUMO
A number of recent investigators have hypothesised a link between autism, left-handedness, and brain laterality. Their findings have varied widely, in part because these studies have relied on different methodologies and definitions. We conducted a systematic review and meta-analysis to assess the literature, with the hypothesis that there would be an association between autism and laterality that would be moderated by handedness, sex, age, brain region studied, and level of autism. From a broad search resulting in 259 papers, 54 were identified for inclusion in the literature review. This list was narrowed further to include only studies reporting results in the inferior frontal gyrus for meta-analysis, resulting in four papers. The meta-analysis found a moderate but non-significant effect size of group on lateralisation, suggesting a decrease in strength of lateralisation in the autistic group, a trend supported by the literature review. A subgroup analysis of sex and a meta-regression of handedness showed that these moderating variables did not have a significant effect on this relationship. Although the results are not conclusive, there appears to be a trend towards a relationship between autism and lateralisation. However, more rigorous studies with better controls and clearer reporting of definitions and results are needed.
Assuntos
Transtorno Autístico/patologia , Transtorno Autístico/fisiopatologia , Lateralidade Funcional/fisiologia , Mãos/fisiopatologia , HumanosRESUMO
OBJECTIVE: To report the burden and correlates of poor physical performance in a diverse cohort of individuals with systemic lupus erythematosus (SLE). METHODS: In this single-visit study of 446 individuals with SLE from a population-based metropolitan Atlanta cohort, we measured physical performance via the Short Physical Performance Battery (score range 0-12; intermediate-low [<10] vs high [≥10]). We also collected demographic, clinical, and psychosocial variables and examined the associations (adjusted odds ratios [aORs]) of intermediate-low versus high physical performance with these characteristics via multivariable logistic regression. RESULTS: We found that more than half (59.6%) of our participants had poorer (intermediate-low) overall physical performance. Only 7% of the cohort received the maximum score on the lower body strength task versus 90% and 76% receiving the maximum scores on balance and gait speed tasks. Current employment status (aOR 0.69, 95% confidence interval [CI] 0.45-1.05) and higher cognitive functioning (aOR 0.57, 95% CI 0.42-0.77) were strongly associated with lower odds of intermediate-low physical performance. Higher body mass index (aOR 1.25, 95% CI 1.01-1.56), disease activity (aOR 1.59, 95% CI 1.27-1.98), and disease burden (aOR 1.38, 95% CI 1.08-1.77) were associated with poorer performance, as were higher depressive symptoms, perceived stress scores, and lower educational attainment (not statistically significant). CONCLUSION: In our population-based, primarily Black cohort, we found that individuals with SLE commonly had poor physical performance. We identified both SLE- and non-SLE-specific factors that could help clinicians identify those most at risk for poor physical performance and intervene to improve, maintain, and support physical performance among those with SLE.
Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Escolaridade , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Desempenho Físico Funcional , Efeitos Psicossociais da Doença , Estudos TransversaisRESUMO
OBJECTIVE: We sought to describe fluid cognition and its correlates among individuals with systemic lupus erythematosus (SLE). METHODS: Participants (n = 199) were recruited from a population-based cohort for a single study visit (October 2019 to May 2022). Fluid cognition was measured via the National Institutes of Health Toolbox Fluid Cognition Battery (including episodic memory, working memory, attention and inhibitory control, processing speed, and cognitive flexibility domains) and expressed as age-corrected standard scores (mean 100, SD 15). Potential impairment was defined as a standard score >1.5 SD below the mean. Descriptive statistics were calculated and associations of various participant characteristics with the potential fluid cognition impairment were assessed with multivariable logistic regression. RESULTS: Participants' mean age was 46.1 years; most were female (87.4%), Black (86.4%), and non-Hispanic (95.0%). The mean overall fluid cognition score was 87.2; of the individual domains, the participants' mean score was lowest on attention and inhibitory control (82.0). Working status (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.14-0.64) and higher self-reported physical functioning (OR 0.46, 95% CI 0.28-0.75) and physical performance (OR 0.72, 95% CI 0.59-0.87) were associated with lower odds of fluid cognition impairment; lower educational attainment was associated with higher odds (OR 3.82, 95% CI 1.67-8.75). Self-reported forgetfulness, neuropsychiatric damage, and depressive symptoms were not statistically significantly associated with potential impairment. CONCLUSION: Fluid cognition and, particularly, attention and inhibitory control were low in those with SLE relative to the general US population. Working status, higher physical functioning and performance, and higher educational attainment were associated with lower prevalence of potential impairment. Future work is needed to develop and implement interventions to help support cognition in individuals with SLE.