Editorial: A Roadmap for Advancing the Field in Early-Onset Psychosis.

The number of umbrella reviews, the systematic reviews of all systematic reviews and meta-analyses in a specified subject, have increased exponentially in recent years. In February 2024, a PubMed search with the term "umbrella review" yielded 840 publications in 2023, compared with 77 in 2013, and 16 in 2003. As the number of scientific publications grows, also does the need to synthesize the current state of knowledge to guide research efforts, clinical practice, and health policies.1,2.

Brain functional activation and first mood episode in youth at risk for bipolar disorder.

BACKGROUND: In order to identify biomarkers of prodromal mood disorders, we examined functional brain activation in children and adolescent at familial risk for bipolar disorder. METHODS: Offspring of parents with bipolar I disorder (at-risk youth; N = 115, mean ± SD age: 13.6 ± 2.7; 54 % girls) and group-matched offspring of healthy parents (healthy controls; N = 58, mean ± SD age: 14.2 ± 3.0; 53 % girls) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. At baseline, at-risk youth had no history of mood episodes or psychotic disorders. Subjects were followed longitudinally until developing their first mood episode or being lost to follow-up. Standard event-related region-of-interest (ROI) analyses were performed to compare brain activation at baseline between groups and in survival analyses. RESULTS: At baseline, at-risk youth exhibited reduced activation to emotional distracters in the right ventrolateral prefrontal cortex (VLPFC) (p = 0.04). Activation was not significantly altered in additional ROIs, including left VLPFC, bilateral amygdala, caudate, or putamen. In those at-risk youth who developed their first mood episode during follow-up (n = 17), baseline increased activation in right VLPFC, right caudate, and right putamen activation predicted the development of a mood episode. LIMITATIONS: Sample size of converters, loss to follow-up, and number of statistical comparisons. CONCLUSIONS: We found preliminary evidence that a reduced activation in right VLPFC might be a marker of risk for or resilience to mood disorders in at-risk youth. Conversely, an increased activation in the right VLPFC, caudate, and putamen might indicate an increased risk for the later development of their first mood episode.

Hospital resource utilisation from HPV-related diseases in England: a real-world cost analysis.

BACKGROUND AND OBJECTIVE: HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The objective of this study was to quantify the lifetime economic burden of HPV-related diseases based on hospital resources from the perspective of National Health Service (NHS) in England. METHODS: Patients' data were extracted, anonymised and aggregated by NHS digital from Hospital Episode Statistics (HES) database of patients admitted in 2015 and followed for three years. Data on hospitalizations were identified according to the International Classification of Diseases (ICD-10 CM). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the hospitalization costs of anal, cervical, genital, oropharyngeal cancers as well as anogenital warts and cervical dysplasia. RESULTS: A total of 19,296 hospitalized patients were included in the estimation model, (39% was male and 61% female. At admission, the average age was 60 and 50 years old, respectively). Life-time costs per patients diagnosed with oropharyngeal cancer were £16,911 (£17,142 for male and £16,334 for female), penile cancer £12,539, vaginal cancer £12,676, anal cancer £13.773 (£12,590 for male, £14,525 for female). Cervical cancer accounted for £12,721, whereas cervical dysplasia for £3932. Resource used for hospitalized patients with anogenital warts was equal to £872 (£884 and £856 for men and women, respectively). On average, outpatient accounted for 39% of the total lifetime costs. CONCLUSION: The results of this study highlight that a substantial amount of resources is utilized for the treatment of HPV-related diseases at hospital level in England. These measures have the potential to inform policy decisions to ensure an optimal use of the NHS resources.

Dual-porosity micromodels for studying multiphase fluid flow in carbonate rocks.

Carbonate rocks usually present a wide variation in pore size within a sample and may contain macroscopic pores ranging from a few millimeters to microscopic pores smaller than one micrometer. Therefore, studying the fluid flow inside carbonates presents a challenging problem. This study proposes a methodology to create dual-porosity micromodels for studying single and two-phase fluid flow in multiscale, carbonate-like, rocks. For this purpose, a design technique for Rock-on-a-Chip (ROC) devices based on the Voronoi tessellation was extended to take into account bimodal pore size distributions, allowing the creation of a macroporous system made up of larger channels and vugs that can be filled with distinct microporosity types. The porous media thus generated were then employed to fabricate polymer micromodels by applying the soft lithography technique. Experimental and numerical results show that the microporosity can increase or reduce the permeability, depending on whether it is added to the grains and/or to the large channels. Even when the microporous matrix completely filled the large channels, the addition of vugs did not increase the permeability. Regarding two-phase fluid flow, the location of the steady-state fluids after drainage clearly depends on the proportion and spatial distribution of microporosity, as well as its type. For the micromodel with microporous grains, no significant amount of wetting fluid was displaced from the micropores. In contrast, when microporosities fill the large channels, the injected fluid forces the displacement of the wetting liquid from the micropores, although far from effectively. The novel approach presented in this work represents a step forward in the artificial generation of more representative micromodels for studying fluid flow at the pore scale.

Changes in the structural brain connectome over the course of a nonrandomized clinical trial for acute mania.

Disrupted topological organization of brain functional networks has been widely reported in bipolar disorder. However, the potential clinical implications of structural connectome abnormalities have not been systematically investigated. The present study included 109 unmedicated subjects with acute mania who were assigned to 8 weeks of treatment with quetiapine or lithium and 60 healthy controls. High resolution 3D-T1 weighted magnetic resonance images (MRI) were collected from both groups at baseline, week 1 and week 8. Brain networks were constructed based on the similarity of morphological features across brain regions and analyzed using graph theory approaches. At baseline, individuals with bipolar disorder illness showed significantly lower clustering coefficient (Cp) (p = 0.012) and normalized characteristic path length (λ) (p = 0.004) compared to healthy individuals, as well as differences in nodal centralities across multiple brain regions. No baseline or post-treatment differences were identified between drug treatment conditions, so change after treatment were considered in the combined treatment groups. Relative to healthy individuals, differences in Cp, λ and cingulate gyrus nodal centrality were significantly reduced with treatment; changes in these parameters correlated with changes in Young Mania Rating Scale scores. Baseline structural connectome matrices significantly differentiated responder and non-responder groups at 8 weeks with 74% accuracy. Global and nodal network alterations evident at baseline were normalized with treatment and these changes associated with symptomatic improvement. Further, baseline structural connectome matrices predicted treatment response. These findings suggest that structural connectome abnormalities are clinically significant and may be useful for predicting clinical outcome of treatment and tracking drug effects on brain anatomy in bipolar disorder. CLINICAL TRIALS REGISTRATION: Name: Functional and Neurochemical Brain Changes in First-episode Bipolar Mania Following Successful Treatment with Lithium or Quetiapine. URL: https://clinicaltrials.gov/ . REGISTRATION NUMBER: NCT00609193. Name: Neurofunctional and Neurochemical Markers of Treatment Response in Bipolar Disorder. URL: https://clinicaltrials.gov/ . REGISTRATION NUMBER: NCT00608075.

Structural connectivity associated with familial risk for mental illness: A meta-analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders.

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable conditions with overlapping genetic liability. Transdiagnostic and disorder-specific brain changes associated with familial risk for developing these disorders remain poorly understood. We carried out a meta-analysis of diffusion tensor imaging (DTI) studies to investigate white matter microstructure abnormalities in relatives that might correspond to shared and discrete biomarkers of familial risk for psychotic or mood disorders. A systematic search of PubMed and Embase was performed to identify DTI studies in relatives of SCZ, BD, and MDD patients. Seed-based d Mapping software was used to investigate global differences in fractional anisotropy (FA) between overall and disorder-specific relatives and healthy controls (HC). Our search identified 25 studies that met full inclusion criteria. A total of 1,144 relatives and 1,238 HC were included in the meta-analysis. The overall relatives exhibited decreased FA in the genu and splenium of corpus callosum (CC) compared with HC. This finding was found highly replicable in jack-knife analysis and subgroup analyses. In disorder-specific analysis, compared to HC, relatives of SCZ patients exhibited the same changes while those of BD showed reduced FA in the left inferior longitudinal fasciculus (ILF). The present study showed decreased FA in the genu and splenium of CC in relatives of SCZ, BD, and MDD patients, which might represent a shared familial vulnerability marker of severe mental illness. The white matter abnormalities in the left ILF might represent a specific familial risk for bipolar disorder.

N-acetylcysteine for depression and glutamate changes in the left prefrontal cortex in adolescents and young adults at risk for bipolar disorder: A pilot study.

AIMS: To investigate the mechanism of action of N-acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder. METHODS: We conducted an 8-week open label clinical trial of NAC 2400 mg/days in 15-24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC). RESULTS: Nine participants were enrolled and finished the study. NAC significantly improved depressive and anxiety symptom scores, and clinical global impression (all p < .001). There was a non-significant reduction in glutamate levels in the left VLPFC. Reduction in depressive symptom scores was positively associated with reduction in glutamate levels in the left VLPFC (p = .007). CONCLUSIONS: This pilot study suggests that NAC might be efficacious for depressive symptoms in at-risk youth, and that its mechanism of action involves the modulation of glutamate in the left VLPFC.

Higher mortality during COVID-19 pandemic in socially vulnerable areas in Belo Horizonte: implications for vaccination prioriti / Maior mortalidade durante a pandemia de COVID-19 em áreas socialmente vulneráveis em Belo Horizonte: implicações para priorização da vacinação

Objective: To assess mortality during the COVID-19 pandemic according to social vulnerability by areas of Belo Horizonte (BH), aiming at strategies for vaccination. Methods: Ecological study with mortality analysis, according to census tracts classified by the Health Vulnerability Index, a composite indicator that includes socioeconomic and sanitation variables. Deaths due to natural causes and COVID-19 were obtained from the "Mortality Information System", between the 10th and 43rd epidemiological weeks (EW) of 2020. Excess mortality was calculated by a time series model, considering observed deaths by EW, between 2015 and 2019, for census tracts. Mortality rates (MR) were calculated and age-standardized =using population estimates from 2010 census. Results: Excess mortality in BH was 16.1% (n =1524): 11.0%, 18.8% and 17.3% in the low, intermediate and high vulnerability areas, respectively. The differences between observed and expected age-standardized MR by natural causes were equal to 59/100,000 inhabitants in BH, increasing from 31 to 77 and 95/100,000 inhabitants, in the areas of low, intermediate and high vulnerability, respectively. There was an aging gradient in COVID-19 MR, ranging from 4 to 611/100,000 inhabitants among individuals of 20-39 years and 75+ years. The COVID-19 MR per 100,000 elderly (60+ years) was 292 in BH, increasing from 179 to 354 and 476, in the low, intermediate and high vulnerability areas, respectively. Conclusion: Inequalities in mortality, particularly among the elderly, combined with the limited supply of doses, demonstrate the importance of prioritizing socially vulnerable areas during vaccination against COVID-19.

Objetivo: Avaliar a mortalidade por áreas de Belo Horizonte (BH) durante a pandemia de COVID-19 conforme vulnerabilidade social, visando estratégia de vacinação. Métodos: Estudo ecológico com análise de mortalidade, segundo setores censitários classificados pelo Índice de Vulnerabilidade da Saúde, composto por indicadores de saneamento e socioeconômicos. Óbitos por causas naturais e COVID-19 foram obtidos do Sistema de Informação sobre Mortalidade, entre a 10ª e 43ª semana epidemiológica (SE) de 2020. Calculou-se o excesso de mortalidade por modelo de série temporal, considerando as mortes observadas por SE, entre 2015 e 2019, por setor censitário. Taxas de mortalidade (TM) foram calculadas e padronizadas por idade a partir de estimativas populacionais do IBGE. Resultados: Houve 16,1% (n=1524) de excesso de mortalidade em BH: 11,0%, 18,8% e 17,3% nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. As diferenças entre TM observadas e esperadas por causas naturais, padronizadas por idade, foi igual a 59/100.000 habitantes em BH, aumentando de 31 para 77 e 95/100.000, nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. Houve gradiente de aumento com a idade nas TM por COVID-19, variando de 4 a 611/100.000 habitantes entre as idades de 20-39 anos e 75+ anos. A TM por COVID-19 por 100.000 idosos (60+ anos) foi igual a 292, aumentando de 179 para 354 e 476, nos setores de baixa, média e elevada vulnerabilidade, respectivamente. Conclusão: Desigualdades na mortalidade, mesmo entre idosos, aliadas à baixa oferta de doses, demonstram importância de priorizar áreas socialmente vulneráveis durante a vacinação contra COVID-19.

Changes in the brain structural connectome after a prospective randomized clinical trial of lithium and quetiapine treatment in youth with bipolar disorder.

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.

Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder

Objective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. Results: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). Conclusions: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Previous studies and meta-analyses suggested that N-acetylcysteine (NAC) was superior to placebo in improving depression in bipolar disorder. However, more recent data, including two larger trials, found that NAC was no more effective than placebo. We conducted a meta-analysis to appraise the possible efficacy of NAC in treating bipolar depression. METHODS: A systematic review and meta-analysis of double-blind, placebo-controlled trials of NAC as a treatment augmentation strategy for bipolar depression was carried out in PubMed (1966-2020). We utilized random-effect analysis to evaluate improvement in depressive symptoms from baseline to endpoint as the primary efficacy measure. RESULTS: Six trials including 248 patients were included. Treatment augmentation with NAC showed a moderate effect size favoring NAC over placebo (d = 0.45, 95% C.I.: 0.06-0.84). There was substantial heterogeneity (I2  = 49%). Meta-regression analyses did not identify any moderator that might explain variation in heterogeneity, including baseline depressive symptom scores, mean NAC dose, or duration of study. CONCLUSIONS: Results from six clinical trials suggest that treatment augmentation with NAC for bipolar depression appears to be superior to placebo, with a moderate effect size, but a large confidence interval. Larger clinical trials, investigating possible moderating factors, such as NAC dose, treatment duration, baseline depression severity, or chronicity of illness, are warranted.

Individual prediction of symptomatic converters in youth offspring of bipolar parents using proton magnetic resonance spectroscopy.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Water contamination with atrazine: is nitric oxide able to improve Pistia stratiotes phytoremediation capacity?

Atrazine is an herbicide commonly used in several countries. Due to its long half-life, associated with its use in large scales, atrazine residues remain as environmental pollutants in water bodies. Phytoremediation is often pointed out as an interesting approach to remove atrazine from the aquatic environment, but its practical application is limited by the high toxicity of this herbicide. Here, we characterize the damages triggered by atrazine in Pistia stratiotes, evaluating the role of nitric oxide (NO), a cell-signaling molecule, in increasing the tolerance to the pollutant and the phytoremediation potential of this species. Pistia stratiotes plants were exposed to four treatments: Control; Sodium nitroprusside (SNP) (0.05 mg L-1); Atrazine (ATZ) (150 µg L-1) and ATZ + SNP. The plants remained under those conditions for 24 h for biochemical and physiological analysis and 3 days for the evaluation of relative growth rate. The presence of atrazine in plant cells triggered a series of biochemical and physiological damages, such as the increase in the generation of reactive oxygen species, damages to cell membranes, photosynthesis impairment, and negative carbon balance. Despite this, the plants maintained greater growth rates than other aquatic macrophytes exposed to atrazine and showed high bioconcentration and translocation factors. The addition of SNP, a NO donor, decreased the herbicide toxicity, with an increase of over 60% in the IC50 value (Inhibitor Concentration). Indeed, the NO signaling action was able to increase the tolerance of plants to atrazine, which resulted in increments in pollutant uptake and translocation, with the maintenance of overall cell (e.g. membranes) and organs (root system) structure, and the functioning of central physiological processes (e.g. photosynthesis). These factors allowed for more quickly and efficient removal of the pollutant from the environment, reducing costs, and increasing the viability of the phytoremediation process.

Vinegar from Anacardium othonianum Rizzini using submerged fermentation.

BACKGROUND: Anacardium othonianum Rizzini is a native Cerrado fruit, recently described in the literature. Its use is restricted to its native region and there is a lack of studies regarding production of vinegar from the pulp. This work aims to investigate the production of A. othonianum Rizzini vinegar using submerged fermentation. RESULTS: The density, alcohol content, proximal composition, pH, color coordinates, and chromatographic profile of the volatile compounds were analyzed in the slurry, fermented juice, and vinegar produced from the corpulent parts of A. othonianum Rizz. Sensory acceptance and willingness to pay were also assessed with vinegar at 4% and 6% of total acidity. The results indicated compliance with European legislation and the presence of volatile compounds such as carbon dioxide, acetic acid, ethanol, and acetaldehyde in the analyzed vinegars. Our results indicate the potential of vinegar production from A. othonianum, with 74% and 86% willingness to pay. CONCLUSIONS: The process of transformation of the fruit pulp into new products can contribute to fruit valorization and consequent preservation of the plant in the Cerrado biome. To the best of our knowledge, this is the first report of volatile compounds and minerals in A. othonianum Rizz. slurry. Our observations can be used as a basis for future studies regarding the preparation of vinegars from this species and for investigating their application in cooking and guiding consumer perception. © 2020 Society of Chemical Industry.

Evidence of drought memory in Dipteryx alata indicates differential acclimation of plants to savanna conditions.

The remarkable phytogeographic characteristics of the Brazilian savanna (Cerrado) resulted in a vegetation domain composed of plants with high structural and functional diversity to tolerate climate extremes. Here we used a key Cerrado species (Dipteryx alata) to evaluate if species of this domain present a mechanism of stress memory, responding more quickly and efficiently when exposed to recurrent drought episodes. The exposure of D. alata seedlings to drought resulted in several changes, mainly in physiological and biochemical traits, and these changes differed substantially when the water deficit was imposed as an isolated event or when the plants were subjected to drought cycles, suggesting the existence of a drought memory mechanism. Plants submitted to recurrent drought events were able to maintain essential processes for plant survival when compared to those submitted to drought for the first time. This differential acclimation to drought was the result of orchestrated changes in several metabolic pathways, involving differential carbon allocation for defense responses and the reprogramming and coordination of primary, secondary and antioxidant metabolism. The stress memory in D. alata is probably linked the evolutionary history of the species and reflects the environment in which it evolved.

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder.

OBJECTIVE: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). METHODS: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. RESULTS: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). CONCLUSIONS: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

A Novel Method Using Confocal Laser Scanning Microscopy for Three-Dimensional Analysis of Human Dental Enamel Subjected to Ceramic Bracket Debonding.

The aim of this in vitro study was to present a method using confocal laser scanning microscopy for three-dimensional analysis of human dental enamel subjected to ceramic bracket debonding. The labial enamel surfaces of three upper central incisors were prepared and mounted in the form of standardized specimens. A sample repositioning protocol was established to enable surface measurement and analysis before and after bracket debonding. Observations were made of representative areas measuring 1,280 × 1,280 µm2, in the center of the enamel samples, as well as of the total topography (2,500 × 3,500 µm) of the bonding areas provided by the equipment software. Noncontact three-dimensional high-resolution image analyses revealed the capabilities of the employed technique and methodology to permit the examination of specific characteristics and alterations on the surfaces, before and after the debonding and finishing procedures. The new protocol was effective to provide qualitative and quantitative assessments of changes on the same dental surfaces at different trial times. The methodology constitutes a feasible tool for revealing the effects of debonding of ceramic brackets on sound and previously injured dental enamel surfaces.

A new carbon nanomaterial solid-phase microextraction to pre-concentrate and extract pesticides in environmental water.

This research describes a solid-phase microextraction device using carbon nanomaterials supported on steel threads. The device was used to pre-concentrate and extract 24 pesticides in water. The carbon nanomaterials were obtained by a chemical vapor deposition (CVD) process, using methane and acetonitrile as carbon source. The different pesticides were separated, detected, and quantified using gas chromatography coupled to mass spectrometry (GC-MS). The system, optimized and validated in the laboratory, presented good results. Linearity was between 0.0007 and 50.00 µg L-1, with determination coefficients greater than 0.9. The detection and quantification limits were in the range of 0.0002-1.1309 µg L-1 and 0.0007-3.7320 µg L-1, respectively. The studied pesticides presented recovery values in the range of 70 ± 8 to 123 ± 18%. Carbon nanomaterials exhibited high thermal and mechanical resistance, as the same fiber could be used for approximately 300 extractions. The device was applied to analyze environmental water samples collected from the São Francisco river basin in Brazil and in the Chinampas in Mexico City.

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study.

OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.