Attitudes toward depression among Ecuadorian physicians using the Spanish-validated version of the Revised Depression Attitude Questionnaire (R-DAQ).

PURPOSE: Depression is inadequately recognized and managed, and physicians' attitudes toward this condition and its treatment may play a part in this. This study aimed to assess Ecuadorian physicians' attitudes toward depression. METHODS: This was a cross-sectional study conducted using the validated Revised Depression Attitude Questionnaire (R-DAQ). The questionnaire was delivered to Ecuadorian physicians, and the response rate was 88.8%. RESULTS: 76.4% of participants had never received previous training in depression, and 52.1% of them indicated neutral or limited professional confidence when dealing with depressed patients. More than two-thirds of the participants reported an optimistic attitude toward the generalist perspective of depression. CONCLUSION: Overall, physicians in Ecuador's healthcare settings were optimistic and held positive attitudes toward patients with depression. However, a lack of confidence in the management of depression and a need for ongoing training were found, especially among medical professionals who are not in daily contact with patients with depression.

To evaluate whether there is a relationship between occlusion and body posture as delineated by a stabilometric platform: A systematic review.

OBJECTIVE: To evaluate whether there is a relationship between occlusion and body posture evaluated using a stabilometric platform. METHODS: Observational studies that analyzed the relationship between dental occlusion (changes in mandibular position and/or dental malocclusion) and body posture evaluated with a stabilometric platform in patients older than 13 years without orthodontic or orthopedic intervention and systemically healthy were considered eligible for inclusion. PubMed, EMBASE, Science Direct, LILACS, and Google Scholar databases were searched to obtain articles published from September 2019 up to March 2020. RESULTS: Twelve articles met the inclusion criteria, of which 66.7% showed a relationship between dental occlusion and body posture, and 33.3% found no relationship. The marked heterogeneity between studies did not allow data to be combined for meta-analyses. CONCLUSION: For the mandibular positions, the postural changes were mainly in the mediolateral direction, while in the malocclusions, they were in the anteroposterior direction.

Effects of nutrient restriction and subsequent realimentation in pregnant beef cows: Maternal endocrine profile, umbilical hemodynamics, and mammary gland development and hemodynamics.

Our hypothesis was that maternal nutrient restriction would negatively impact the endocrine and metabolic status of the pregnant cow, therefore influencing the mammary gland in preparation for lactation. We further hypothesized that earlier timing of realimentation could prevent negative impacts of nutrient restriction. The objectives were to investigate the influence of nutrient restriction and realimentation during early to late gestation on endocrine profile, umbilical hemodynamics, and mammary gland development and hemodynamics in pregnant beef cows. In Experiment 1, on d 30 of pregnancy cows (initial BW = 667.5 ± 13.4 kg, BCS = 6.2 ± 0.1) were randomly assigned to one of 3 treatments: 1) 100% NRC requirements from d 30 to 254 of gestation (CCC; n = 6); 2) 60% NRC from d 30 to 85, thereafter being re-alimented to 100% NRC to d 254 (RCC; n = 5); 3) or receive 60% NRC from d 30 to 140, thereafter being re-alimented to 100% NRC to d 254 (RRC; n = 6). Cows were returned to a common outdoor facility for calving thereafter and were fed ad libitum. In Experiment 2, on d 30 of pregnancy, cows (initial BW = 620.5 ± 11.3 kg, BCS = 5.1 ± 0.1) were randomly assigned to dietary treatments including: control (CON; 100% NRC; n = 18) and nutrient restriction (RES; 60% NRC; n = 30). On d 85 of pregnancy, cows were either slaughtered (CON, n = 6 and RES, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12) treatments, or were realimented to control (RC; n = 11). On d 140 of pregnancy, cows were either slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5), or were realimented to control (RRC, n = 6). On d 254 of pregnancy, all remaining cows were slaughtered (CCC, n = 6; RCC, n = 5; RRC, n = 6). Mammary hemodynamics and endocrine profile were measured. Serum urea nitrogen, NEFA, as well as fetal parameters were measured in Experiment 1; whereas in Experiment 2, mammary gland development was recorded. In Experiment 1, RRC cows had lower dry matter intake (P = 0.001) and consequently lower BW change (P = 0.06). However, maternal nutrition did not alter mammary hemodynamics, hormonal patterns, and fetal characteristics (P > 0.11). In Experiment 2, CCC cows had increased (P = 0.02) mammary gland blood flow ipsilateral to the gravid horn as well as greater (P = 0.02) mammary gland fat on d 254. Nevertheless, plane of nutrition did not alter hormonal concentrations nor mammary gland characteristics (P > 0.15). These data indicate that nutrient restriction did not alter mammary hemodynamics nor endocrine profile throughout gestation.

The Risk of Cardiovascular Disease Among Immigrants in Canada.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. The global surge in migration to high-income countries, especially Canada, highlights the importance of studies evaluating the risk factors and the disparities in the rate of incidence of CVD among immigrants. Canada is home to a diverse group of immigrants, each presenting with a risk profile that is unique to their ethnicity and country of birth. A variety of cardiac risk factors, such as dietary habits, physical activity, smoking, cultural traditions as well as preponderance to certain diseases like type II diabetes mellitus, hypertension, and high lipid levels act in concert and impact CVD risk and overall incidence. This narrative review focuses on CVD risks and how it is related to the immigration status among various ethnic groups in Canada.

Association and epistatic analysis of white matter related genes across the continuum schizophrenia and autism spectrum disorders: The joint effect of NRG1-ErbB genes.

BACKGROUND: Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. METHODS: We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. RESULTS: Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. DISCUSSION: Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.

Deep Vein Thrombosis in Intravenous Drug Users: An Invisible Global Health Burden.

The prevalence of intravenous drug use has increased in the past decade and it represents an important risk factor for deep vein thrombosis. Intravenous drug use is a global problem, with the main culprit being heroin. Peer pressure and poverty in high-risk groups such as sex workers, females, and young adults raise the risk of intravenous drug use, which expresses itself in the form of venous thromboembolism eventually. Deep vein thrombosis typically manifests itself eight years after the initial intravenous drug administration, rendering it a silent killer. Aiming to review and summarize existing articles in this context, we performed an exhaustive literature search online on PubMed and Google Scholar indexes using the keywords "Deep Venous Thrombosis (DVT)" and "Intravenous Drug Users (IVDU)." English articles that addressed epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, management, and outcomes of DVT, including those in IVDU, were selected and analyzed. The pathogenesis of DVT development in IVDU is mainly attributed to the interplay of trauma to the vessel by repeated injection and the injected drug itself. The right-sided femoral vein is the most common vein affected. Prevalent clinical presentations include local pain, swelling, and redness with typical systemic symptoms including fever, cough, dyspnea, and chest pain on top of addiction features. There appeared to be a delay in reporting symptoms, which was most likely due to the social stigma attached to IVDU. There are over 50 conditions that present with swollen and painful limbs comparable to DVT in IVDU, making precise diagnosis critical for timely treatment. Venous ultrasound is the method of choice for diagnosing DVT. Extended anticoagulant therapy with low-molecular-weight heparin combined with warfarin is the recommended treatment. Intravenous drug abusers having DVT are affected by multiple complications and poorer outcomes such as slower recovery, recurrent venous thromboembolism (VTE), and a longer hospital stay, which put them at higher risk of morbidity, mortality, reduced productivity, and economic burden.

Quality of life and psychiatric comorbidities in pediatric patients with Gilles de la Tourette syndrome. / Calidad de vida y comorbilidades psiquiátricas en pacientes pediátricos con síndrome de Gilles de la Tourette.

INTRODUCTION: Tourette Syndrome (TS) is a complex neurodevelopmental disorder which is normally associated to psychiatric comorbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety or depression. Quality of life (QoL) in these patients can be affected by tic severity and associated comorbidities. AIM: The aim of the study was to describe and analyze QoL and psychiatric comorbidities in a sample of pediatric patients, as well as to develop a Spanish version of the questionnaire CandA-GTS-QoL to measure quality of life in this population. PATIENTS AND METHODS: Single-center, observational, prospective study. Patients aged 6 to 16 years old with TS were included. Demographic, clinical, diagnostic and treatment data were gathered. Questionnaires regarding tic severity, psychiatric comorbidity and quality of life were used. RESULTS: Twenty-two patients with DSM-5 diagnosis of TS were included (86.4% male, median age 11 years). Of those, 86.4% had been previously diagnosed of psychiatric comorbidities and 72.7% received psychopharmacologic treatment. The prevalence of an ICD-10 current diagnosis of anxiety was 72.7%, depression 50%, ADHD 40.9% and OCD 7.3%. Median QoL score was 59.5 (RIC: 34.8-71.3) for PedsQL, and 55.5 (RIC: 45-65) for CandA-GTS-QoL, with a correlation between scores of R2 = 0.83 (p < 0.01). Higher tic severity was associated with poorer QoL (PedsQL R2: -0.732, p <0.01, CandA-GTS-QoL R2: -0.501, p = 0.021). A higher EDAH score for ADHD was associated with poorer QoL (PedsQL R2: -0.463, p = 0.03, CandA-GTS-QoL R2-0.534, p < 0.01). CONCLUSION: Prevalence of psychiatric comorbidities in pediatric TS is high and frequently underdiagnosed. Tics and psychiatric comorbidities affect quality of life. Further studies are needed to validate the Spanish version of CandA-GTS-QoL scale.

TITLE: Calidad de vida y comorbilidades psiquiátricas en pacientes pediátricos con síndrome de Gilles de la Tourette.Introducción. El síndrome de Gilles de la Tourette es un trastorno complejo que se acompaña habitualmente de comorbilidades psiquiátricas, como trastorno por déficit de atención/hiperactividad (TDAH), trastorno obsesivo-compulsivo (TOC), ansiedad o depresión. La calidad de vida de estos pacientes puede verse afectada por la gravedad de los tics y por la presencia de estas comorbilidades. Objetivos. Describir y relacionar la calidad de vida y las comorbilidades psiquiátricas en una muestra de pacientes pediátricos con síndrome de Gilles de la Tourette, así como proporcionar una versión en español del cuestionario Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (CandA-GTS-QOL) para medir la calidad de vida en esta población. Pacientes y métodos. Es un estudio transversal, observacional y unicéntrico. Se incluyó a pacientes entre 6 y 16 años con diagnóstico de síndrome de Tourette, de los cuales se recogieron datos demográficos y clínicos, así como diagnósticos y tratamientos previos. Se entregaron cuestionarios de gravedad de los tics, comorbilidad psiquiátrica y calidad de vida. Resultados. Se incluyó a 22 pacientes (86,4%, varones; mediana de edad, 11 años) con diagnóstico de síndrome de Gilles de la Tourette (según los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición). El 86,4% tenía comorbilidades psiquiátricas diagnosticadas y el 72,7% recibía algún tratamiento. La prevalencia de ansiedad fue del 72,7%, la de depresión, del 50%, la de TDAH, del 40,9% y la de TOC, del 27,3%. La mediana de calidad de vida medida por el Pediatric Quality of Life Inventory (PedsQL) fue de 59,5 (rango intercuartílico: 34,8-71,3), y por la CandA-GTS-QOL, de 55,5 (rango intercuartílico: 45-65) (R2, 0,83; p menor de 0,01). La gravedad de los tics se relacionó con una peor calidad de vida (PedsQL, R2: ­0,707; p menor de 0,01; y CandA-GTS-QOL, R2: ­0,501; p = 0,021). Una mayor puntuación la escala de Conners revisada para el TDAH se relacionó con peor calidad de vida (PedsQL, R2: ­0,463; p = 0,03; y CandA-GTS-QOL, R2: ­0,534; p menor de 0,01). Conclusión. La prevalencia de comorbilidades psiquiátricas en el síndrome de Gilles de la Tourette en nuestro medio es alta y frecuentemente infradiagnosticada. Los tics y las comorbilidades psiquiátricas afectan a la calidad de vida. Son necesarios estudios que validen la CandA-GTS-QOL.

Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 µg, 25 µg and 50 µg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.

Insight into the role of copper in the promoted photocatalytic removal of NO using Zn2-xCuxCr-CO3 layered double hydroxide.

In this work the ability of Zn2-xCuxCr-CO3 layered double hydroxides (LDHs) as highly efficient DeNOx photocatalysts was studied. LDHs with x = 0, 0.2 and 0.4 were prepared using a coprecipitation method. The samples were characterized by different techniques such as XRD, XPS, FT-IR, ICP-MS, TG, SBET, SEM and Diffuse reflectance (DR). The increased amount of copper ions in the LDH layers gave rise to slight changes in the structure and morphology and an important variation of the optical properties of the LDHs. The prepared ZnCuCr-CO3 photocatalysts exhibited favourable conversion efficiency (51%) and an extraordinary selectivity (97%) for the photochemical NO abatement. The photochemical mechanism was elucidated from DOS, EPR, Femtosecond transient absorption and in-situ DRIFTS studies. The results suggested that the presence of Cu2+ ions in the LDH framework introduced new states in the valence band states, thus favouring the production and mobility of e-/h+ charge carriers and a greater production of ⋅O2- and ⋅OH.

Social Cognition in Autism and Schizophrenia Spectrum Disorders: The Same but Different?

Social cognition impairment is a core shared phenotype in both schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD). This study compares social cognition performance through four different instruments in a sample of 147 individuals with ASD or SSD and in healthy controls. We found that both clinical groups perform similarly to each other and worse than healthy controls in all social cognition tasks. Only performance on the Movie for the Assessment of Social Cognition (MASC) test was independent of age and intelligence. Proportionately, individuals in the control group made significantly more overmentalization errors than both patients group did and made fewer undermentalization errors than patients with SSD did. AUC analyses showed that the MASC was the instrument that best discriminated between the clinical and control groups. Multivariate analysis showed negative symptom severity as a potential mediator of the association between social cognition deficit and poor global functioning.

Molecular signatures of atherosclerotic plaques: An up-dated panel of protein related markers.

Atherosclerosis remains the leading cause of ischemic syndromes such as myocardial infarction or brain stroke, mainly promoted by plaque rupture and subsequent arterial blockade. Identification of vulnerable or high-risk plaques constitutes a major challenge, being necessary to identify patients at risk of occlusive events in order to provide them with appropriate therapies. Clinical imaging tools have allowed the identification of certain structural indicators of prone-rupture plaques, including a necrotic lipidic core, intimal and adventitial inflammation, extracellular matrix dysregulation, and smooth muscle cell depletion and micro-calcification. Additionally, alternative approaches focused on identifying molecular biomarkers of atherosclerosis have also been applied. Among them, proteomics has provided numerous protein markers currently investigated in clinical practice. In this regard, it is quite uncertain that a single molecule can describe plaque rupture, due to the complexity of the process itself. Therefore, it should be more accurate to consider a set of markers to define plaques at risk. Herein, we propose a selection of 76 proteins, from classical inflammatory to recently related markers, all of them identified in at least two proteomic studies analyzing unstable atherosclerotic plaques. Such panel could be used as a prognostic signature of plaque instability.

Scaling, rotation, and channeling behavior of helical and skyrmion spin textures in thin films of Te-doped Cu2OSeO3.

Topologically nontrivial spin textures such as vortices, skyrmions, and monopoles are promising candidates as information carriers for future quantum information science. Their controlled manipulation including creation and annihilation remains an important challenge toward practical applications and further exploration of their emergent phenomena. Here, we report controlled evolution of the helical and skyrmion phases in thin films of multiferroic Te-doped Cu2OSeO3 as a function of material thickness, dopant, temperature, and magnetic field using in situ Lorentz phase microscopy. We report two previously unknown phenomena in chiral spin textures in multiferroic Cu2OSeO3: anisotropic scaling and channeling with a fixed-Q state. The skyrmion channeling effectively suppresses the recently reported second skyrmion phase formation at low temperature. Our study provides a viable way toward controlled manipulation of skyrmion lattices, envisaging chirality-controlled skyrmion flow circuits and enabling precise measurement of emergent electromagnetic induction and topological Hall effects in skyrmion lattices.

Effectiveness of pharmaceutical care for drug treatment adherence in women with lupus nephritis in Rio de Janeiro, Brazil: a randomized controlled trial.

OBJECTIVE: Studies have been conducted to determine the causal factors and clinical consequences of non-adherence to treatment in systemic lupus erythematosus (SLE). However, no interventions have been performed to increase drug adherence. Our objective was to assess the effectiveness of pharmaceutical care (PC) for drug treatment adherence in lupus nephritis (LN). METHODS: This was a randomized clinical trial (pragmatic trial) in patients with LN in Rio de Janeiro, Brazil, allocated in two groups: an intervention group (Dader Method for PC) and a control group (institution's usual care). Drug treatment adherence was measured by the combination of five questions normally used in clinical practice. RESULTS: A total of 131 patients were randomized, and 122 completed the study, with a mean follow-up of 12.7 months and use of six drugs per day and 10-12 doses per day. Low adherence was observed at baseline (intervention group: 30%; control group: 29%). PC showed 27% effectiveness (95% confidence interval (CI) -6% to 50%) in the intention to treat analysis and 31% (95% CI 0-52%) in per protocol analysis, considering all drugs. As for adherence to specific drugs for SLE, effectiveness of PC was 64% (95% CI 34-80%) with intention-to-treat analysis and 62% (95% CI 32-79%) in per protocol analysis. CONCLUSIONS: PC was effective for increasing drug treatment adherence in SLE. The detailed account provided by the Dader Method of the difficulties with patients' drug therapy proved invaluable to approach non-adherence.

A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results.

We report the data from the guideline-compliant two-year toxicology study conducted as part of the Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA). BPA (0, 2.5, 25, 250, 2,500, and 25,000 µg/kg body weight (bw)/day) was administered daily by gavage in 0.3% carboxymethylcellulose vehicle to NCTR Sprague-Dawley rats from gestation day 6 through the start of parturition and then directly to pups from the day after birth until postnatal day 21 (stop-dose arm) or continuously until termination at one or two years. The stop-dose arm was included to assess the potential for any BPA effects that were due to developmental exposure. No BPA-related effects were evident in the in-life and non-histopathology data. Neoplastic and nonneoplastic lesions diagnosed in both females and males were common age-associated lesions that were variable across control and BPA-treated groups. The lack of consistent responses within the continuous- and stop-dose arms within and across tissues brought into question the plausible relationship of most of these lesions to BPA treatment. There was a possible relationship between the increased incidences of lesions in the female reproductive tract and the male pituitary and exposure to the 25,000 µg BPA/kg bw/day dose level.

Effects of maternal nutrient restriction followed by realimentation during early and mid-gestation in beef cows. II. Placental development, umbilical blood flow, and uterine blood flow responses to diet alterations.

The objectives were to examine the effects of maternal nutrient restriction followed by realimentation during early to mid-gestation on placental development and uterine and umbilical hemodynamics in the beef cow. On day 30 of pregnancy, multiparous, non-lactating beef cows (620.5 ±â€¯11.3 kg) were assigned to 1 of 2 dietary treatments: control (C; 100% National Research Council [NRC] recommendations; n = 18) and restricted (R; 60% NRC; n = 30). On day 85, cows were slaughtered (C, n = 6; R, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12), or were realimented to control (RC; n = 11). On day 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5), or were realimented to control (RRC, n = 6). On day 254, all remaining cows were slaughtered. Heart rate and umbilical and uterine hemodynamics [blood flow, resistance index (RI), and pulsatility index (PI)] were determined via Doppler ultrasonography. As expected umbilical blood flow increased and fetal heart rate decreased as gestation advanced. Umbilical PI in RRC cows was less (P = 0.01) compared to RCC and CCC. During late gestation, RCC cows had greater (P = 0.02) ipsilateral and total uterine blood flow vs. CCC and RRC. There was an increase in the number and weight of placentomes from R cows (P ≤ 0.02) compared to C cows (i.e. day 85). There were more placentomes (P = 0.03) in RR vs. CC and RC cows, but placentome weight was not affected (P = 0.18) by maternal dietary treatment at day 140. Maternal nutrient restriction during early to mid-gestation increased the weight (by day 85) and number (day 85 and 140) of placentomes, and did not reduce fetal weight compared to control cows. A longer realimentation period may enhance uterine blood flow and individual placentome size during later gestation, which may compensate for reduced nutrients experienced early in gestation.

Hyperprolactinemia-inducing antipsychotics increase breast cancer risk by activating JAK-STAT5 in precancerous lesions.

BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1. RESULTS: We found that the two hyperprolactinemia-inducing antipsychotics, risperidone and pimozide, prompted precancerous lesions to progress to cancer while aripiprazole, which did not cause hyperprolactinemia, did not. We observed that risperidone and pimozide (but not aripiprazole) caused precancerous cells to activate STAT5 and suppress apoptosis while exerting no impact on proliferation. Importantly, we demonstrated that these effects of antipsychotics on early lesions required the STAT5 gene function. Furthermore, we showed that only two-week treatment of mice with ruxolitinib, a JAK1/2 inhibitor, blocked STAT5 activation, restored apoptosis, and prevented early lesion progression. CONCLUSIONS: Hyperprolactinemia-inducing antipsychotics instigate precancerous cells to progress to cancer via JAK/STAT5 to suppress the apoptosis anticancer barrier, and these cancer-promoting effects can be prevented by prophylactic anti-JAK/STAT5 treatment. This preclinical work exposes a potential breast cancer risk from hyperprolactinemia-inducing antipsychotics in certain patients and suggests a chemoprevention regime that is relatively easy to implement compared to the standard 5-year anti-estrogenic treatment in women who have or likely have already developed precancerous lesions while also requiring hyperprolactinemia-inducing antipsychotics.

Uteroplacental secretion of progesterone and estradiol-17ß in an ovine model of intrauterine growth restriction.

Using a mid to late gestation model of intrauterine growth restriction, uteroplacental secretion of progesterone and estradiol-17ß were examined. From day 50 to 130 of gestation, 31 ewe lambs were allocated to receive 100% (ADQ) or 60% (RES) of nutrient requirements. At day 130, umbilical and uterine artery blood flows were determined and blood samples were collected from maternal saphenous artery, gravid uterine vein, umbilical vein, and umbilical artery. Uteroplacental secretion of progesterone was increased in RES compared to ADQ fed dams. There was a net secretion and net metabolism of estradiol-17ß in RES, and ADQ fed dams, respectively. In relation to steroid synthesis, cotyledonary abundance of steroidogenic acute regulatory protein was greater in RES compared with ADQ fed dams, while abundance of aromatase was not different between dietary treatments. Caruncular aldo-keto reductase 1C abundance was less in RES compared to ADQ fed dams. The increase in progesterone secretion, therefore, is due in part to an increase in synthesis and a decrease in placental catabolism. Caruncular cytochrome P450 3A, which catalyzes the conversion of estrogens to catechol-estrogens, was in lesser abundance in RES compared to ADQ fed dams. Opposite responses in estradiol-17ß uteroplacental secretion compared with metabolism may be mediated through placental estrogen metabolism via cytochrome P450 enzymes.

Comparação de métodos in vitro para a quantificação da digestibilidade da matéria seca e da fibra em detergente neutro de forragens e concentrados / Comparison of in vitro methods to quantify the dry matter and neutral detergent fiber digestibility of forages and concentrates

Objetivou-se comparar a digestibilidade in vitro da matéria seca (DIVMS) e da fibra em detergente neutro (DIVFDN) de forragens e concentrados obtidos por intermédio das incubadoras DaisyII e TE-150, combinadas com filter bags tipo F57 (Ankon®) ou tecido não-tecido (TNT, 100g/m²), em relação aos valores obtidos utilizando-se o método de Tilley e Terry (1963). Foram utilizadas 25 amostras de alimentos concentrados e 25 de forragens. Não houve diferenças entre filter bags (P>0,39) para a DIVMS de forragens. Maiores valores de DIVMS (P<0,01) foram verificados para a incubadora TE-150 em relação à DaisyII. As estimativas de DIVMS obtidas com incubadoras e filter bags foram superiores (P<0,01) àquelas obtidas com o método Tilley e Terry (1963). Observaram-se maiores valores de DIVFDN de forragens (P<0,01) com filter bags F57 em relação ao TNT e com a incubadora TE-150 em relação à DaisyII. Todos os valores de DIVFDN obtidos com incubadoras e filter bags foram superiores (P<0,01) aos obtidos com o método Tilley e Terry (1963). Todos os métodos apresentaram-se positiva e fortemente correlacionados (P<0,01), tanto para DIVMS como para DIVFDN. As repetibilidades e variâncias entre amostras para DIVMS e DIVFDN foram similares entre os métodos. Portanto, conclui-se que, em se tratando de avaliações comparativas entre alimentos, todos os métodos avaliados possuem capacidade similar de discriminação.(AU)

The objective was to compare in vitro digestibility of dry matter (IVDMD) and neutral detergent fiber (IVNDFD) of forages and concentrates obtained using the incubators DaisyII and TE-150, and filter bags F57 (Ankon®) or non-woven textile (NWT - 100g/m²) in comparison with the values obtained using the Tilley and Terry (1963) method. Twenty-five samples of concentrates and 25 samples of forages were used. There were no differences between filter bags (P>0.39) for IVDMD of forages. Higher IVDMD (P<0.01) were observed for TE-150 compared to DaisyII. Estimates of IVDMD obtained with incubators and filter bags were higher (P<0.01) than those obtained with the Tilley and Terry (1963) method. Higher IVNDFD (P<0.01) were obtained with filter bags F57 regarding to NWT and TE-150 when compared to DaisyII. All values of the IVNDFD obtained with incubators and filter bags were higher (P<0.01) than those obtained with the Tilley and Terry (1963) method. Both IVDMD and IVNDFD variables were greater using TE-150 incubator than using DaisyII (P<0.04). Estimates obtained using NWT filter bags were higher (P<0.01) than F57 filter bags. All methods were positively and strongly correlated (P<0.01) to each other for IVDMD and IVNDFD. The repeatability and variances among samples for IVDMD and IVNDFD were similar among methods. In conclusion, all methods were similarly able to discriminate samples.(AU)

Insular pathology in young people with high-functioning autism and first-episode psychosis.

BACKGROUND: Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions. METHODS: Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored. RESULTS: Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = -0.28, p = 0.041) and left posterior (r = -0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of 'autistic-like' symptoms (r = -0.30, p = 0.028). CONCLUSIONS: The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.