The GNE-KLH anti-cocaine vaccine protects dams and offspring from cocaine-induced effects during the prenatal and lactating periods.

Protecting children from prenatal cocaine exposure is a significant challenge for physicians and childbearing women with cocaine use disorder. Cocaine use is highly prevalent among reproductive-aged women and prenatal cocaine exposure produces obstetric, foetal neurodevelopmental and long-term behavioural impairments. Cocaine crosses the maternal and foetal blood-brain barrier and the placenta by diffusion. The best approach to prevent prenatal cocaine exposure is to stop cocaine use. However, only 25% of cocaine users can discontinue their use during pregnancy. Anti-cocaine vaccination decreases cocaine passage through the blood-brain barrier. This study describes an innovative approach for preventing prenatal cocaine exposure using the GNE-KLH anti-cocaine vaccine, a novel use for the named anti-drug vaccines. Here, we show that anti-cocaine vaccination with GNE-KLH produced and maintained anti-cocaine IgG antibody titres and avidity during pregnancy. These antibodies protected the pregnant rats and their pups against prenatal cocaine damage during pregnancy until weaning. The present work is the first preclinical evidence of the efficacy of an innovative mechanism to prevent prenatal cocaine exposure damage, a worldwide public health care issue. In the future, this mechanism may be useful in pregnant women with cocaine use disorder. Further studies to understand the mechanisms of how anti-cocaine antibodies exert their protective effects in pregnancy are warranted.

Suicidality among pregnant women in Brazil: prevalence and risk factors.

Suicide is one of the major causes of preventable death. We evaluated suicidality among pregnant women who participated in prenatal care in Brazil. A total of 255 patients were assessed using semi-structured interviews as well as the Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory (BDI), and Mini-International Neuropsychiatric Interview (MINI) Plus. Thereafter, Stata 12 was used to identify the significant predictors of current suicide risk (CSR) among participants using univariate and multivariate analyses (p < 0.05). According to MINI Plus module C, the lifetime suicide attempt rate was 12.55%. The overall CSR was 23.53%, distributed across risk levels of low (12.55%), moderate (1.18%), and high (9.80%). Our rates approximate those found in another Brazilian study (18.4%). Antenatal depression (AD), lifetime bipolar disorder, and any current anxiety disorder (as measured using the MINI) as well as BDI scores ≥15 and EPDS scores ≥11 were identified as positive risk factors in a univariate analysis (p < 0.001). These factors changed after a multivariate analysis was employed, and only years of education [odds ratio (OR) = 0.45; 95% confidence intervals (CIs) = 0.21-0.99], AD (OR = 3.42; 95% CIs = 1.37-8.53), and EPDS scores ≥11 (OR = 4.44; 95% CIs = 1.97-9.97) remained independent risk factors. AD and other psychiatric disorders were the primary risk factors for suicidality, although only the former remained an independent factor after a multivariate analysis. More than 10 years of education and EPDS scores ≥11 were also independent factors; the latter can be used as a screening tool for suicide risk.

The role of FGF-2/HGF and fibronectin matrix on pleomorphic adenoma myoepithelial cell morphology and immunophenotype: an in vitro study.

Myoepithelial cells play a central role in glandular tumors, regulating the progression of in situ to invasive neoplasias, with the tumor microenvironment being shown to be involved in both initiation and progression. This study aimed to analyze the in vitro effects of fibroblast growth factor-2 (FGF-2) and hepatocyte growth factor (HGF) in myoepithelial cells under the influence of the fibronectin matrix extracellular protein. Benign myoepithelial cells were obtained from pleomorphic adenoma and cultured on a fibronectin substratum. FGF-2 and HGF were supplemented at different concentrations and time intervals, in order to evaluate cell proliferation, morphology and immunophenotype. Individually, FGF-2 and HGF supplementation did not alter myoepithelial cell proliferation, morphology or immunophenotype. The fibronectin substratum provoked an increase in cell proliferation and immunopositivity for α-smooth muscle actin and FGF-2. The myoepithelial cell morphology changed when the fibronectin substratum and FGF-2 acted together, highlighting the importance of the fibronectin extracellular matrix protein on the behavior of these cells.

Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades.

OBJECTIVES: The aim of this study was to characterize the prevalence and patterns of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade. METHODS: The cohort comprised 533 INI-naive subjects and 255 raltegravir recipients with viraemia who underwent integrase sequencing in routine care across Europe, including 134/533 (25.1%) and 46/255 (18.0%), respectively, with non-B clades (A, C, D, F, G, CRF01, CRF02, other CRFs, complex). RESULTS: No major INI resistance-associated mutations (RAMs) occurred in INI-naive subjects. Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). In addition, four (1.6%) raltegravir recipients showed novel mutations at recognized resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other integrase positions that were statistically associated with raltegravir exposure (K159Q/R, I161L/M/T/V, E170A/G). Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). Intermediate- to high-level cross-resistance to twice-daily dolutegravir was predicted in 40/255 (15.7%) subjects, more commonly in subtype B versus non-B clades (39/209, 18.7% versus 1/46, 2.2%; P = 0.003). A glycine (G) to serine (S) substitution at integrase position 140 required one nucleotide change in subtype B and two nucleotide changes in all non-B clades. CONCLUSIONS: No major INI resistance mutations occurred in INI-naive subjects. Reduced occurrence of Q148H/R/K + G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the G140S mutation observed in all non-B clades analysed.

Ticks (Acari: Ixodidae) on swifts (Apodiformes: Apodidae) in Minas Gerais, southeastern Brazil.

Brazil harbors five species of Cypseloidinae swifts. Those from Streptoprocne and Cypseloides genera have a very distinct ecology. They shelter at night and build nests in moist cliffs by waterfalls. Information about tick infestation of these birds is virtually non-existent and restricted to the description of a new species, Ixodes paranaensis, in Streptoprocne biscutata in Paraná State and another record of this species in Streptoprocne zonaris in Minas Gerais State. We herein report tick infestation of swifts at eight waterfalls in the Cerrado biome of Minas Gerais State, southeastern Brazil. Swifts were captured during six campaigns from November 2008 to April 2013. Overall, 584 swifts were captured (527 C. senex, four C. fumigatus and 53 S. zonaris). Four birds were tick infested (prevalence of 0.7 %). Three individuals of C. senex hosted one tick each; a nymph of I. paranaensis, a female of I. paranaensis and a nymph of Amblyomma cajennense. One S. zonaris hosted an I. paranaensis nymph and an Ornithodoros sp. larva (Argasidae).

Pharmacologic treatment of sex offenders with paraphilic disorder.

Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even eliminate deviant sexual behavior in sex offenders with paraphilic disorders. In this article, we will review pharmacological treatment options for sex offenders with paraphilias. Both serotonin selective reuptake inhibitors (SSRIs) and antiandrogen treatments have been used with reported success in decreasing recidivism. SSRIs have been used in mild types of paraphilias and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe sex offenders with paraphilic disorders in order to reduce victimization. Combined pharmacological and psychotherapeutic treatment is associated with better efficacy. Imaging studies may improve the knowledge of paraphilic disorders and the mechanisms of action of current treatments. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of treatments.

[Schizophrenia: research perspectives]. / Grands axes de recherche sur la schizophrénie.

Current data and perspectives for schizophrenia research were reviewed in this paper. Increased incidence of schizophrenia is correlated to perinatal environmental factors, recent immigration, urban life and cannabis. Determining endophenotypes seems to be a promising strategy in the field of molecular genetics. Side effects and efficacy of treatments for schizophrenia could, now, be better predicted by the use of pharmacogenetic studies. Functional neuroimaging studies have described hypoactivations of certain brain areas supporting the hypothesis of a dysfunction of inner speech during auditory and verbal hallucinations. Dopaminergic and glutamatergic systems are disturbed in schizophrenia. These data contribute to a better understanding of the disease and may help to decrease the stigma that surrounds schizophrenia.

Safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate model.

A promising strategy for cocaine addiction treatment is the anti-drug vaccine. These vaccines induce the production of anticocaine antibodies, capable of linking to cocaine, and decrease the passage of cocaine throughout the blood-brain barrier, decreasing drug activity in the brain. Our research group developed a new vaccine candidate, the UFMG-V4N2, to treat cocaine use disorders (CUD) using an innovative carrier based on calixarenes. This study assessed the safety and immunogenicity of the anti-cocaine vaccine UFMG-VAC-V4N2 in a non-human primate toxicity study using single and multiple vaccine doses. The UFMG-VAC-V4N2 yielded only mild effects in the injection site and did not influence the general health, feeding behavior, or hematological, renal, hepatic, or metabolic parameters in the vaccinated marmosets. The anti-cocaine vaccine UFMG-VAC-V4N2 presented a favorable safety profile and induced the expected immune response in a non-human primate model of Callithrix penicillata. This preclinical UFMG-VAC-V4N2 study responds to the criteria required by international regulatory agencies contributing to future anticocaine clinical trials of this anti-cocaine vaccine.

Prevalence of psychiatric symptoms and associated factors in the adult population from the area affected by the tailings dam rupture - Brumadinho Health Project.

OBJECTIVE: To examine the prevalence of psychiatric symptoms and associated factors in the adult population of Brumadinho (MG), after the dam collapse. METHODS: We included 2,740 participants with information about symptoms of post-traumatic stress disorder (PTSD), depression, anxiety, thoughts of death/self-harm, and poor sleep quality collected in 2021. Prevalence values of all conditions were estimated to compare the prevalence of psychiatric symptoms with the participants' sociodemographic characteristics and place of residence. Pearson's c2 test was used, with Rao Scott's correction. Crude and adjusted logistic regressions estimated odds ratios and 95% confidence intervals to assess the association between psychiatric symptoms and participants' characteristics. RESULTS: The most common condition was depressive symptoms (29.3%), followed by post-traumatic stress symptoms (22.9%) and anxious symptoms (18.9%). Regarding the association between participants' characteristics in the adjusted analysis, being a female and living in a mining area was positively associated with symptoms of PTSD, depression, anxiety, thoughts of death/self-harm, and poor sleep quality. A positive association was also found between high school education and post-traumatic stress symptoms. In contrast a negative association was found between being aged ≥60 years and symptoms of PTSD, depression, and anxiety. CONCLUSION: High prevalence values were found for all psychiatric symptoms after the dam failure in Brumadinho. Being a female, living in the mining area, being ≥60 years old, and having an educational level were all associated with the psychiatric symptoms investigated.

Eating disorders are associated with adverse obstetric and perinatal outcomes: a systematic review.

OBJECTIVE: To systematically review the literature focusing on obstetric and perinatal outcomes in women with previous or current eating disorders (EDs) and on the consequences of maternal EDs for the offspring. METHODS: The study was performed following the systematic review and meta-analysis (PRISMA) statement. PubMed, SciELO, and Cochrane databases were searched for non-interventional studies published in English or Portuguese from January 1980 to December 2020. Risk of bias was assessed using the Methods guide for effectiveness and comparative effectiveness reviews (American Agency for Healthcare Research and Quality). RESULTS: The search yielded 441 records, and 30 articles were included. The psychiatric outcome associated with EDs in women was mainly perinatal depression. The most prevalent obstetric outcomes observed in women with EDs were vomiting, hyperemesis, bleeding, and anemia. Most studies found maternal anorexia nervosa and bulimia nervosa to be associated with low birth weight and slow fetal growth. Women with binge EDs delivered children with increased birth weight. Of the 30 studies included, methodological quality was good in seven, fair in eight, and poor in 15 studies. CONCLUSION: A considerable body of evidence was reviewed to assess obstetric and perinatal outcomes in EDs. Acute and lifetime EDs, especially if severe, correlated with poor perinatal, obstetric, and neonatal outcomes. Obstetricians and general practitioners should be vigilant and screen for EDs during pregnancy.

Calix[n]arene-based immunogens: A new non-proteic strategy for anti-cocaine vaccine.

Introduction: Cocaine use disorder is a significant public health issue without a current specific approved treatment. Among different approaches to this disorder, it is possible to highlight a promising immunologic strategy in which an immunogenic agent may reduce the reinforcing effects of the drug if they are able to yield sufficient specific antibodies capable to bind cocaine and/or its psychoactive metabolites before entering into the brain. Several carriers have been investigated in the anti-cocaine vaccine development; however, they generally present a very complex chemical structure, which potentially hampers the proper assessment of the coupling efficiency between the hapten units and the protein structure. Objectives: The present study reports the design, synthesis and preclinical evaluation of two novel calix[n]arene-based anti-cocaine immunogens (herein named as V4N2 and V8N2) by the tethering of the hydrolysis-tolerant hapten GNE (15) on calix[4]arene and calix[8]arene moieties. Methods: The preclinical assessment corresponded to the immunogenicity and dose-response evaluation of V4N2 and V8N2. The potential of the produced antibodies to reduce the passage of cocaine analogue through the blood-brain-barrier (BBB), modifying its biodistribution was also investigated. Results: Both calix[n]arene-based immunogens elicited high titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue (99mTc-TRODAT-1) and decreased cocaine-induced behavior, according to an animal model. Conclusion: The present results demonstrate the potential of V4N2 and V8N2 as immunogens for the treatment of cocaine use disorder.

The Brazilian version of the SCOFF questionnaire to screen eating disorders in young adults: cultural adaptation and validation study in a university population.

OBJECTIVE: This study translated, culturally adapted, and validated a Brazilian Portuguese version (SCOFF-BR) of the Sick, Control, One Stone, Fat, Food Questionnaire (SCOFF) to screen eating disorders in young adults. METHODS: This study used back-translation to culturally adapt the questionnaire according to International Society of Pharmacoeconomics and Outcome Research principles. The SCOFF-BR validation process involved a sample of men and women aged 18-32 years from a university community. After the participants completed the SCOFF-BR questionnaire, pre-trained researchers interviewed them with the Mini International Neuropsychiatric Interview (MINI). The presence of eating disorders was determined according to DSM-5 criteria. RESULTS: Of the 361 subjects, 9.7% had an eating disorder (2.2% anorexia nervosa, 5% bulimia nervosa, and 2.5% binge-eating disorder). Using a cutoff point of two positive responses, we obtained a sensitivity of 80% and a specificity of 71.5%, with an accuracy of 72.3%. The positive and negative predictive values were 23.1% and 97.1%, respectively. CONCLUSION: This study demonstrated that the Brazilian version of the SCOFF questionnaire presents satisfactory accuracy and reliability to screen eating disorders among young adults in the Brazilian university community.

Sexual addictions.

UNLABELLED: The potential adverse consequences, personal distress, shame and guilt presented by patients who suffer from sexual addiction require a more in-depth understanding of the phenomenology and psychobiology of this disorder. METHODS: A bibliographic review was conducted using MEDLINE and EBSCO databases with the following keywords: "sexual addiction," "hypersexuality," "compulsive sexual behavior," "behavioural addiction," "treatment," and "addiction." RESULTS: Several conceptualizations of excessive nonparaphilic sexual disorder have been proposed based on the models of, respectively, obsessive compulsive disorder, impulse control disorder, out of control excessive sexual disorder, and addictive disorder. Despite the lack of robust scientific data, a number of clinical elements, such as the frequent preoccupation with this type of behavior, the time spent in sexual activities, the continuation of this behavior despite its negative consequences, the repeated and unsuccessful efforts made to reduce the behavior, are in favor of an addictive disorder. In addition there is a high comorbidity between excessive sexual behavior and other addictive behaviors. CONCLUSION: The phenomenology of excessive nonparaphilic sexual disorder favors its conceptualization as an addictive behavior, rather than an obsessive-compulsive, or an impulse control disorder. Moreover, the criteria that are quite close to those of addictive disorders were recently proposed for the future DSM-V in order to improve the characterization of this condition. Finally, controlled studies are warranted in order to establish clear guidelines for treatment of sexual addiction.

Skeletal muscle mass index and phase angle are decreased in individuals with dependence on alcohol and other substances.

OBJECTIVE: The aim of this study was to evaluate whether low skeletal muscle mass index (SMI) and low phase angle (PhA) are associated with demographic, clinical, lifestyle, and nutritional status in patients dependent on alcohol and other substances. METHODS: We prospectively included 63 individuals dependent on alcohol and other substances and 71 age- and sex-matched healthy controls. Body composition was assessed by bioelectrical impedance analysis. Subjective global assessment was used to evaluate malnutrition. All included participants underwent a psychiatric evaluation, including the administration of the Mini-International Neuropsychiatric Interview. Univariate and multivariate analysis were performed to evaluate associations between low skeletal muscle mass index (SMI) and low phase angle (PhA) and nutritional, lifestyle, and alcohol use and cocaine/crack use variables, controlling for sex and age. RESULTS: Low SMI and low PhA were identified in 11.1% and 44.5% of the substance dependents, respectively. Low midarm muscle circumference (r = 0.58; P < 0.001), low midarm muscle area (r = 051; P < 0.001), and reduced PhA (r = 0.59; P < 0.001) were positively correlated with low SMI. Multivariate analysis showed that heavy alcohol consumption (≥80 g·d· ≥5 y-1; odds ratio [OR], 2.33; 95% confidence interval [CI], 1.12-4.84; P = 0.02) and sedentary lifestyle (OR, 4.39; 95% CI, 1.29-14.89; P = 0.02) were independently associated with reduced SMI. Low PhA was independently associated with heavy alcohol consumption (OR, 3.64; 95% CI, 1.62-8.15; P = 0.002) and cocaine or crack use (OR, 3.97; 95% CI, 1.05-15.11; P = 0.04) in multivariate analysis. CONCLUSIONS: Low SMI and low PhA are independently associated with heavy alcohol consumption. Low PhA is independently associated with cocaine or crack use.

Obsessive compulsive disorder as a cause of atypical eating disorder: a case report.

OBJECTIVE: To describe a case of an atypical eating disorder with a diagnosis of obsessive-compulsive disorder and discuss the phenomenological and neurobiological aspects links between the disorders. CASE: a 20-year-old Caucasian woman presented with obsessive-compulsive disorder followed by altered eating habits with major weight loss and amenorrhea. The medical workup, treatment and outcome are described. Using cognitive-behavioural therapy, clomipramine and enteral nutrition, weight gain and disappearance of restrictive and obsessive-compulsive behaviours were obtained. CONCLUSION: Available evidence in the literature suggests a continuum in eating disorder and obsessive compulsive disorder. Our case illustrates that an obsessive-compulsive disorder may precede or precipitate the development of an eating disorder and highlights the importance of a precise differential diagnosis in eating disorders clinics.

First record of haemosporidian parasites infecting swifts (Aves: Apodidae).

Avian malaria is a widespread infection caused by parasites from the Order Haemosporida. Indeed, Neotropical swifts are interesting models for host-parasite coevolution studies due to their unique life history that may allow them to escape parasitism. Considering this, we evaluated haemosporidians from Neotropical swifts. We collected blood and prepared smears from 277 individuals from waterfalls in Brazil. Despite low parasitemia or absence of parasites detected by microscopy haemosporidian infection was detected in 44 swifts (15.8%) using a screening PCR that amplifies a 154-nucleotide segment of ribosomal RNA coding sequence within the mitochondrial DNA (mtDNA) of Plasmodium and Haemoproteus. Although previous studies reported absence of these parasites in European and North American swifts our data suggest that Neotropical swifts are susceptible to haemosporidians. Further studies will add information about evolutionary and ecological aspects of avian haemosporidia in Neotropical Cypseloidinae swifts.

Smartphone and Facebook addictions share common risk and prognostic factors in a sample of undergraduate students.

INTRODUCTION: To improve the comprehension of the interface between smartphone addiction (SA) and Facebook addiction (FA), we hypothesize that the occurrence of both technological addictions correlate, with higher levels of negative consequences. Moreover, we hypothesize that SA is associated with lower levels of social support satisfaction. METHODS: We recruited a convenience sample of undergraduate students from Universidade Federal de Minas Gerais, with age ranging between 18 and 35 years. All subjects completed a self-fulfilled questionnaire comprising sociodemographic data, the Brazilian Smartphone Addiction Inventory (SPAI-BR), the Bergen Scale for Facebook Addiction, the Barrat Impulsivity Scale 11 (BIS-11), the Social Support Satisfaction Scale (SSSS), and the Brief Sensation Seeking Scale (BSSS-8). After completing the questionnaire, the interviewer conducted a Mini-International Neuropsychiatric Interview (MINI). RESULTS: In the univariate analysis, SA associated with female gender, with ages 18 to 25 years, FA, substance abuse disorders, major depressive disorder, anxiety disorders, low scores in SSSS, high scores in BSSS-8, and high scores in BIS. The group with SA and FA presented a higher prevalence of substance abuse disorders, depression, and anxiety disorders when compared to the group with SA only. CONCLUSION: In our sample, co-occurrence of SA and FA correlated with higher levels of negative consequences and lower levels of social support satisfaction. These results strongly suggest that SA and FA share some elements of vulnerability. Further studies are warranted to clarify the directions of these associations.

Is there a role for cannabidiol in psychiatry?

OBJECTIVES: Understanding whether cannabidiol (CBD) is useful and safe for the treatment of psychiatric disorders is essential to empower psychiatrists and patients to take good clinical decisions. Our aim was to conduct a systematic review regarding the benefits and adverse events (AEs) of CBD in the treatment of schizophrenia, psychotic disorders, anxiety disorders, depression, bipolar disorder and substance-use disorders. METHODS: We conducted a literature search in PubMed, Scielo, and Clinicaltrials.gov databases. Evidence was classified according to the WFSBP task forces standards. RESULTS: Bibliographic research yielded 692 records. After analysis, we included six case reports and seven trials, comprising 201 subjects. Most the studies published presented several drawbacks and did not reach statistical significance. We have not found evidence regarding major depressive and bipolar disorders. The level of evidence for cannabis withdrawal is B; cannabis addiction is C2; treatment of positive symptoms in schizophrenia and anxiety in social anxiety disorder is C1. Discrete or no AEs were reported. The most frequently reported AEs are sedation and dizziness. CONCLUSIONS: The evidence regarding efficacy and safety of CBD in psychiatry is still scarce. Further larger well-designed randomised controlled trials are required to assess the effects of CBD in psychiatric disorders.

Corrigendum: Bad Choices Make Good Stories: The Impaired Decision-Making Process and Skin Conductance Response in Subjects With Smartphone Addiction.

[This corrects the article DOI: 10.3389/fpsyt.2019.00073.].