Comprehensive analysis of clinical images contributions for melanoma classification using convolutional neural networks.

BACKGROUND: Timely diagnosis plays a critical role in determining melanoma prognosis, prompting the development of deep learning models to aid clinicians. Questions persist regarding the efficacy of clinical images alone or in conjunction with dermoscopy images for model training. This study aims to compare the classification performance for melanoma of three types of CNN models: those trained on clinical images, dermoscopy images, and a combination of paired clinical and dermoscopy images from the same lesion. MATERIALS AND METHODS: We divided 914 image pairs into training, validation, and test sets. Models were built using pre-trained Inception-ResNetV2 convolutional layers for feature extraction, followed by binary classification. Training comprised 20 models per CNN type using sets of random hyperparameters. Best models were chosen based on validation AUC-ROC. RESULTS: Significant AUC-ROC differences were found between clinical versus dermoscopy models (0.661 vs. 0.869, p < 0.001) and clinical versus clinical + dermoscopy models (0.661 vs. 0.822, p = 0.001). Significant sensitivity differences were found between clinical and dermoscopy models (0.513 vs. 0.799, p = 0.01), dermoscopy versus clinical + dermoscopy models (0.799 vs. 1.000, p = 0.02), and clinical versus clinical + dermoscopy models (0.513 vs. 1.000, p < 0.001). Significant specificity differences were found between dermoscopy versus clinical + dermoscopy models (0.800 vs. 0.288, p < 0.001) and clinical versus clinical + dermoscopy models (0.650 vs. 0.288, p < 0.001). CONCLUSION: CNN models trained on dermoscopy images outperformed those relying solely on clinical images under our study conditions. The potential advantages of incorporating paired clinical and dermoscopy images for CNN-based melanoma classification appear less clear based on our findings.

CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness.

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f-/- mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.

Lifetime cocaine use is a potential predictor for conversion from major depressive disorder to bipolar disorder: A prospective study.

AIM: We aimed to identify whether lifetime cocaine use is a risk factor for conversion from major depressive disorder (MDD) to bipolar disorder (BD) in an outpatient sample of adults. METHODS: This prospective cohort study included 585 subjects aged 18 to 60 years who had been diagnosed with MDD as assessed by the Mini International Neuropsychiatric Interview (MINI-Plus) at baseline (2012-2015). Subjects were reassessed a mean of 3 years later (2017-2018) for potential conversion to BD as assessed by the MINI-Plus. Lifetime cocaine use was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test. RESULTS: In the second wave, we had 117 (20%) losses, and 468 patients were reassessed. The rate of conversion from MDD to BD in 3 years was 12.4% (n = 58). A logistic regression analysis showed that the risk for conversion from MDD to BD was 3.41-fold higher (95% confidence interval, 1.11-10.43) in subjects who reported lifetime cocaine use at baseline as compared to individuals who did not report lifetime cocaine use at baseline, after adjusting for demographic and clinical confounders. CONCLUSION: These findings showed that lifetime cocaine use is a potential predictor of conversion to BD in an MDD cohort. Further studies are needed to assess the possible underlying mechanisms linking exposure to cocaine with BD conversion.

Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder.

AIM: The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. METHODS: This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. RESULTS: We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. CONCLUSION: Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

Childhood social, emotional, and behavioural problems and their association with behaviour in the dental setting.

BACKGROUND: Mental disorders are among the main causes of global disability in children, with negative impacts on their quality of life. It is possible that mental disorders could be associated with how children react in the dental setting. AIM: To test the association between children's psychological attributes and behaviour presented during dental care. DESIGN: A questionnaire was given to mothers of children attending a paediatric dental clinic. Psychological attributes were evaluated using the Strengths and Difficulties Questionnaire. For analysis, the Internalizing and Externalizing problems and the Prosocial behaviour subscales were considered. Children's behaviour was assessed using the Frankl Scale. For analysis, Poisson regression models were employed. A significant level of P ≤ 0.05 was adopted. RESULTS: Overall, 128 children aged between four and 12 years were included. Total difficulties (PR 5.36; 95%CI 2.2-12.9), Internalizing problems (PR 4.04; 95%CI 1.6-10.0), and externalizing problems (PR 3.36; 1.5-7.7) were associated with uncooperative behaviour. In relation to the strength domain, the Prosocial behaviour subscale (PR 1.21; 95%CI 0.6-2.6) was not associated with child behaviour. CONCLUSIONS: This study provides evidence that children aged between four and 12 years with internalizing and externalizing problems tend to have a higher prevalence of negative behaviour during dental treatment.

Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice.

BACKGROUND AND PURPOSE: Cerebral aneurysm (CA) affects 3% of the population and is associated with hemodynamic stress and inflammation. Myeloperoxidase, a major oxidative enzyme associated with inflammation, is increased in patients with CA, but whether myeloperoxidase contributes to CA is not known. We tested the hypotheses that myeloperoxidase is increased within human CA and is critical for formation and rupture of CA in mice. METHODS: Blood was drawn from the lumen of CAs and femoral arteries of 25 patients who underwent endovascular coiling of CA, and plasma myeloperoxidase concentrations were measured with ELISA. Effects of endogenous myeloperoxidase on CA formation and rupture were studied in myeloperoxidase knockout mice and wild-type (WT) mice using an angiotensin II-elastase induction model of CA. In addition, effects of myeloperoxidase on inflammatory gene expression in endothelial cells were analyzed. RESULTS: Plasma concentrations of myeloperoxidase were 2.7-fold higher within CA than in femoral arterial blood in patients with CA. myeloperoxidase-positive cells were increased in aneurysm tissue compared with superficial temporal artery of patients with CA. Incidence of aneurysms and subarachnoid hemorrhage was significantly lower in myeloperoxidase knockout than in WT mice. In cerebral arteries, proinflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2 (COX2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C motif) ligand (XCL1), matrix metalloproteinase (MMP) 8, cluster of differentiation 68 (CD68), and matrix metalloproteinase 13, and leukocytes were increased, and α-smooth muscle actin was decreased, in WT but not in myeloperoxidase knockout mice after induction of CA. Myeloperoxidase per se increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in endothelial cells. CONCLUSIONS: These findings suggest that myeloperoxidase may contribute importantly to formation and rupture of CA.

Leptin in depressive episodes: is there a difference between unipolar and bipolar depression?

OBJECTIVE: The present study investigated whether peripheral leptin levels are associated with current depressive episodes in a cross-sectional study nested within a population-based study. METHODS: The Mini-International Neuropsychiatric Interview (MINI) 5.0 was used to assess the presence of current depressive episodes. The sample was composed of 206 subjects (103 controls and 103 subjects with a current depressive episode) paired by gender, BMI and age. Medication use and lifestyle characteristics were self-reported. RESULTS: Serum leptin levels were lower in currently depressive subjects (10.9 ± 12.0 ng/ml) than in the control group (20.3 ± 24.0 ng/ml; p = 0.023). According to the clinical diagnosis, individuals with bipolar depression present lower leptin levels (8.4 ± 8.1 ng/ml) than those with unipolar depression (12.0 ± 13.4 ng/ml) and the control group (20.3 ± 24.0 ng/ml; p = 0.031). In addition, ANCOVA showed that leptin is an independent factor associated with current depressive episodes (p = 0.018). CONCLUSION: A decreased leptin level might be a useful peripheral marker associated with depressive episodes in the context of bipolar disorder.

Increased serum neurotrophin levels related to alcohol use disorder in a young population sample.

BACKGROUND: The diagnosis of alcohol use disorder is based on clinical signs and on the measurement of biological markers. However, these markers are neither sufficiently sensitive, nor specific enough, for determining the effects of alcohol abuse on the central nervous system. Serum neurotrophins are important regulators of neural survival, development, function, and plasticity and have been found to be reduced in alcohol use disorder. The aim of this study was to investigate the alterations in serum neurotrophin levels (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF], and nerve growth factor [NGF]) in alcohol use disorder in a young population, and thus possibly representing the early stages of the illness. METHODS: This is a cross-sectional study, nested in a population-based study of people aged 18 to 35, involving 795 participants. The participants responded to the CAGE questionnaire, and a CAGE score of ≥2 was considered to be a positive screen for the abuse/dependence or moderate to severe alcohol use disorder. Serum BDNF, GDNF, and NGF levels were measured by ELISA. RESULTS: In the CAGE ≥ 2 group, GDNF (p ≤ 0.001) and NGF (p ≤ 0.001) serum levels were significantly increased, and the BDNF elevation was near a statistical significance (p = 0.068) when compared to the CAGE < 2 group. A significantly positive correlation was observed only in the CAGE ≥ 2 group for BDNF/GDNF (r = 0.37, p < 0.001) and GDNF/NGF (r = 0.84, p < 0.001) levels. The correlation between the NGF and BDNF levels was significantly positive in both groups (r = 0.28, p < 0.001 for the CAGE < 2 group, and r = 0.30, p = 0.008 for the CAGE ≥ 2 group). CONCLUSIONS: These results suggest that elevated neurotrophins are candidate markers for the early stages of alcohol misuse.

Immune dysfunction in bipolar disorder and suicide risk: is there an association between peripheral corticotropin-releasing hormone and interleukin-1ß?

OBJECTIVE: The aim of the present study was to investigate the relationship between peripheral levels of corticotropin-releasing hormone (CRH) and interleukin-1ß (IL-1ß) in individuals with bipolar disorder (BD) with and without suicide risk (SR), and controls. METHODS: A total of 120 young adults (40 controls, 40 subjects with BD without SR, and 40 subjects with BD with SR) were enrolled from a population-based study carried out in the city of Pelotas, Brazil. BD and SR were assessed through the Mini International Neuropsychiatric Interview (MINI 5.0), and peripheral markers were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of CRH were significantly lower both in subjects with BD without SR (p = 0.04) and subjects with BD with SR (p = 0.02) when compared to controls. However, levels of IL-1ß were increased in subjects with BD with SR (p = 0.05) when compared to controls. Sociodemographic and clinical variables, current mood episode, and use of psychiatric medications were not associated with changes in these markers. No correlation was found between peripheral levels of CRH and IL-1ß (p = 0.60) in the population or in the BD with SR group (p = 0.88). CONCLUSIONS: These results suggest that peripheral mechanisms linking stress hormones and the immune system might be critical patterns involved in suicidal behavior associated with BD.

Psychiatric and substance-use comorbidities associated with lifetime crack cocaine use in young adults in the general population.

OBJECTIVE: To assess the association between lifetime crack cocaine use and psychiatric (post-traumatic stress disorder, current depression, current dysthymia, generalized anxiety disorder, panic disorder with agoraphobia, social phobia, as well as SRQ scores and suicide risk) and substance-use disorders (tobacco, alcohol, cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens and opioids) in youth in the general population of the city of Pelotas, RS. METHOD: This was a cross-sectional population-based study, involving 1560 participants between 18 and 24 ears old. Lifetime substance use and abuse were investigated using the ASSIST inventory. Psychiatric comorbidities were assessed using the Mini-International Neuropsychiatric Interview and symptoms of common mental disorders were evaluated with the Self-Reported Questionnaire (SRQ). RESULTS: The prevalence of lifetime crack cocaine use in the sample was 2.5%. Its use was associated with total SRW scores and the presence of post-traumatic stress disorder, antisocial personality disorder and suicide risk in the final regression model. Tobacco, alcohol, cannabis, cocaine, amphetamine and cocaine dependence were also associated with lifetime use of crack cocaine. DISCUSSION: Youth with a history of crack cocaine use had a higher prevalence of psychiatric conditions such as post-traumatic stress disorder, as well as an increased risk of tobacco, alcohol, cannabis, cocaine, amphetamine and inhalant use and dependence.

Violent and sexual behaviors and lifetime use of crack cocaine: a population-based study in Brazil.

OBJECTIVE: To estimate the prevalence of lifetime use of crack cocaine and to assess associations with violent and sexual behaviors in young adults selected from the general population of Pelotas, Southern Brazil. METHODS: This cross-sectional population-based study included 1,560 participants aged 18-24 years. The use of alcohol and other substances, including crack cocaine, was assessed using the alcohol, smoking and substance involvement screening test. Other variables included violent behaviors, firearm possession, and sexual risk behaviors. The frequency of antisocial personality disorder was also investigated. Associations were analyzed using a crude model and models adjusted for sex, social class, and the use of snorted cocaine. RESULTS: Lifetime prevalence of crack cocaine use was 2.51 %, and it was higher among males and individuals coming from more vulnerable social classes (D or E). In the final multivariate models, lifetime use of crack cocaine was associated with episodes of aggression and firearm possession, as well as with a higher chance of not having used condom in the last sexual intercourse. In less conservative models, crack cocaine use was associated with other violent and sexual risk behaviors. DISCUSSION: The strong association observed between lifetime use of crack cocaine and different violent and sexual risk behaviors underscores relevant characteristics of people who use crack cocaine. Improving our understanding of possible causal chains leading to such associations should be a priority in future studies.

Micro-Addition of Silver to Copper: One Small Step in Composition, a Change for a Giant Leap in Biocidal Activity.

The use of copper as an antimicrobial agent has a long history and has gained renewed interest in the context of the COVID-19 pandemic. In this study, the authors investigated the antimicrobial properties of an alloy composed of copper with a small percentage of silver (Cu-0.03% wt.Ag). The alloy was tested against various pathogens, including Escherichia coli, Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and the H1N1 virus, using contact exposure tests. Results showed that the alloy was capable of inactivating these pathogens in two hours or less, indicating its strong antimicrobial activity. Electrochemical measurements were also performed, revealing that the small addition of silver to copper promoted a higher resistance to corrosion and shifted the formation of copper ions to higher potentials. This shift led to a slow but continuous release of Cu2+ ions, which have high biocidal activity. These findings show that the addition of small amounts of silver to copper can enhance its biocidal properties and improve its effectiveness as an antimicrobial material.

Chemical, enzymatic and cellular antioxidant activity studies of Agaricus blazei Murrill.

Mushrooms possess nutritional and medicinal properties that have long been used for human health preservation and that have been considered by researchers as possible sources of free radical scavengers. In this work, the antioxidant properties of water extracts from Agaricus blazei Murill, produced by maceration and decoction, are demonstrated in vitro. Resistance to oxidation is demonstrated through three mechanisms: i) inhibition of enzymatic oxidative process, with 100% inhibition of HRP (horseradish peroxidase) and MPO (myeloperoxidase); ii) inhibition of cellular oxidative stress, with 80% inhibition of the oxidative burst of polymorphonuclear neutrophils (PMNs); and iii) direct action over reactive species, with 62% and 87% suppression of HOCl and superoxide anion radical (O2• -), respectively. From the data, it was concluded that the aqueous extract of A. blazei has significant antioxidant activity, indicating its possible application for nutraceutical and medicinal purposes.

Impact of ACE2 deficiency and oxidative stress on cerebrovascular function with aging.

BACKGROUND AND PURPOSE: Angiotensin II produces oxidative stress and endothelial dysfunction in cerebral arteries, and angiotensin II type I receptors may play a role in longevity and vascular aging. Angiotensin-converting enzyme type 2 (ACE2) converts angiotensin II to angiotensin (1-7) and thus, may protect against effects of angiotensin II. We hypothesized that ACE2 deficiency increases oxidative stress and endothelial dysfunction in cerebral arteries and examined the role of ACE2 in age-related cerebrovascular dysfunction. METHODS: Endothelial function, expression of angiotensin system components, NADPH oxidase subunits, and proinflammatory cytokines were examined in cerebral arteries from adult (12 months old) and old (24 months old) ACE2 knockout (KO) and wild-type (WT) mice. The superoxide scavenger tempol was used to examine the role of oxidative stress on endothelial function. RESULTS: Vasodilatation to acetylcholine was impaired in adult ACE2 KO (24±6% [mean±SE]) compared with WT mice (52±7%; P<0.05). In old mice, vasodilatation to acetylcholine was impaired in WT mice (29±6%) and severely impaired in ACE2 KO mice (7±5%). Tempol improved endothelial function in adult and old ACE2 KO and WT mice. Aging increased mRNA for tumor necrosis factor-α in WT mice, and significantly increased mRNA levels of NAPDH oxidase 2, p47(phox), and Regulator of calcineurin 1 in both ACE2 KO and WT mice. mRNA levels of angiotensin system components did not change during aging. CONCLUSIONS: ACE2 deficiency impaired endothelial function in cerebral arteries from adult mice and augmented endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging.

DNA fragmentation by gamma radiation and electron beams using atomic force microscopy.

Double-stranded pBS plasmid DNA was irradiated with gamma rays at doses ranging from 1 to 12 kGy and electron beams from 1 to 10 kGy. Fragment-size distributions were determined by direct visualization, using atomic force microscopy with nanometer-resolution operating in non-tapping mode, combined with an improved methodology. The fragment distributions from irradiation with gamma rays revealed discrete-like patterns at all doses, suggesting that these patterns are modulated by the base pair composition of the plasmid. Irradiation with electron beams, at very high dose rates, generated continuous distributions of highly shattered DNA fragments, similar to results at much lower dose rates found in the literature. Altogether, these results indicate that AFM could supplement traditional methods for high-resolution measurements of radiation damage to DNA, while providing new and relevant information.

Sex-dependent role of CD300f immune receptor in generalized anxiety disorder.

Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. It was recently demonstrated that CD300f might be influential in the pathogenesis of depression in a sex-dependent manner. Here, we evaluated the role of CD300f immune receptor in anxiety, using CD300f knockout mice (CD300f-/-) and patients with GAD. We observed that male CD300f-/- mice had numerous behavioral changes associated with a low-anxiety phenotype, including increased open field central locomotion and rearing behaviors, more exploration in the open arms of the elevated plus-maze test, and decreased latency to eat in the novelty suppressed feeding test. In a cross-sectional population-based study, including 1111 subjects, we evaluated a common single-nucleotide polymorphism rs2034310 (C/T) in the cytoplasmatic tail of CD300f gene in individuals with GAD. Notably, we observed that the T allele of the rs2034310 polymorphism conferred protection against GAD in men, even after adjusting for confounding variables. Overall, our data demonstrate that CD300f immune receptors are involved in the modulation of pathological anxiety behaviors in a sex-dependent manner. The biological basis of these sex differences is still poorly understood, but it may provide significant clues regarding the neuropathophysiological mechanisms of GAD and can pave the way for future specific pharmacological interventions.

5-year incidence of suicide-risk in youth: A gradient tree boosting and SHAP study.

BACKGROUND: Machine learning methods for suicidal behavior so far have failed to be implemented as a prediction tool. In order to use the capabilities of machine learning to model complex phenomenon, we assessed the predictors of suicide risk using state-of-the-art model explanation methods. METHODS: Prospective cohort study including a community sample of 1,560 young adults aged between 18 and 24. The first wave took place between 2007 and 2009, and the second wave took place between 2012 and 2014. Sociodemographic and clinical characteristics were assessed at baseline. Incidence of suicide risk at five-years of follow-up was the main outcome. The outcome was assessed using the Mini Neuropsychiatric Interview (MINI) at both waves. RESULTS: The risk factors for the incidence of suicide risk at follow-up were: female sex, lower socioeconomic status, older age, not studying, presence of common mental disorder symptoms, and poor quality of life. The interaction between overall health and socioeconomic status in relation to suicide risk was also captured and shows a shift from protection to risk by socioeconomic status as overall health increases. LIMITATIONS: Proximal factors associated with the incidence of suicide risk were not assessed. CONCLUSIONS: Our findings indicate that factors related to poor quality of life, not studying, and common mental disorder symptoms of young adults are already in place prior to suicide risk. Most factors present critical non-linear patterns that were identified. These findings are clinically relevant because they can help clinicians to early detect suicide risk.

Childhood trauma and bipolar spectrum: a population-based sample of young adults.

Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

OBJECTIVE: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. METHOD: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. RESULTS: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). CONCLUSION: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves.

Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.