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Open-label: the clinical effects of adding cannbidiol to usual care of patients with residual symptoms in the diagnosis of Obsessive Compulsive Disorder
- E. R. De Morais, A. W. Z. P. W. Zuardi, F. S. Guimarães, F. L. Osório, J. E. Hallak, R. F. Sanches, J. A. S. Crippa
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S225-S226
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Introduction
Obsessive-compulsive disorder (OCD) is a heterogeneous and debilitating neuropsychiatric disorder. First-line antidepressants with Selective Serotonin Reuptake Inhibitors (SSRIs) and Clomipramine (a tricyclic antidepressant) are unresponsive or partially responsive in 40% of treated patients. Preclinical studies have shown that cannabidiol (CBD) can reduce compulsive behavior in animals, and considering that the release of glutamate in the action of CBD can inhibit terminal axons of neurons in the corticostriatal-thalamo-cortical circuit, we chosefor testing CBD, a drug with few side effects and low toxicity, as an adjuvant in treating OCD.
ObjectivesTo evaluate the clinical effects of CBD add-on to the usual pharmacological treatment of outpatients diagnosed with OCD.
MethodsMethods: This is an open-label study in which patients received CBD 300mg-day for 30 days in addition to their usual treatments and CBD 600mg-day for an additional 30 days if they have not reduced at least 25% of symptoms compared to the baseline evaluated by the Yale-brown obsessive-compulsive scale (Y-BOCS). Psychometric scales were used to assess the effects of CBD: Y-BOCS, General Anxiety Disorder 7 (GAD-7), Clinical Overall Impressions-Severity (CGI-S), Clinical Global Impressions-Improvement (CGI-I), Patient Health Questionnaire-9 (PHQ-9), Epworth Sleepiness Scale and Udvalg Scale for Kliniske Undersogelser (UKU) scale.
Participants: We initially assessed 33 participants in the study. So far, 19 patients have completed the study. Eleven did not complete the study, and 03 patients are still in the study trial.
ResultsMean (SD) Y-BOCS scores decreased from 28.0 (4.8) at baseline to 13.8 (8.6) at week 8, corresponding to a - 50.7% reduction (P<.0001). Anxiety symptoms (GAD-7 scale) (P=0.001) and CGI-Severity scales scores (P<0.001) improved significantly.
Measure Baseline, Mean (SD) Week 4, Mean (SD) Week 8, Mean (SD) Mean Change (Baseline to Week 4) Mean Change (Baseline to Week 8) Mean (SD) p-value t-test Y-Bocks 28.0 (4.8) 17.8 (7.3) 13.8 (8.6) 10.1 (6.5) <0,001 7.1 14.1 (7.9) <0,001 7.7 GAD-7 13.8 (4.4) 8.14 (4.9) 8.0 (5.7) 5.7 (6.4) 0,001 4.0 5.6 (5.8) 0,001 4.1 CGI-I 5.48 (0.9) 3.9 (1.3) 3.3 (1.5) 1.5 (1.3) <0,001 5.28 2.1 (1.2) <0,001 7.4 a n=22;
b n=19
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ConclusionsWe concluded that there was an important reduction in the psychometric scales used with statistical significance. This is a partial analysis of the results as the study progresses. We believe that in the future we will be able to complete this study and have a better analysis of the results that are promising. At the end of the study, other psychometric scales such as CGI-I, epworth scale and UKU will be analyzed.
Disclosure of InterestNone Declared
Predicting enteric methane production from cattle in the tropics
- R. S. Ribeiro, J. P. P. Rodrigues, R. M. Maurício, A. L. C. C. Borges, R. Reis e Silva, T. T. Berchielli, S. C. Valadares Filho, F. S. Machado, M. M. Campos, A. L. Ferreira, R. Guimarães Júnior, J. A. G. Azevêdo, R. D. Santos, T. R. Tomich, L. G. R. Pereira
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Accurate estimates of methane (CH4) production by cattle in different contexts are essential to developing mitigation strategies in different regions. We aimed to: (i) compile a database of CH4 emissions from Brazilian cattle studies, (ii) evaluate prediction precision and accuracy of extant proposed equations for cattle and (iii) develop specialized equations for predicting CH4 emissions from cattle in tropical conditions. Data of nutrient intake, diet composition and CH4 emissions were compiled from in vivo studies using open-circuit respiratory chambers, SF6 technique or the GreenFeed® system. A final dataset containing intake, diet composition, digestibility and CH4 emissions (677 individual animal observations, 40 treatment means) obtained from 38 studies conducted in Brazil was used. The dataset was divided into three groups: all animals (GEN), lactating dairy cows (LAC) and growing cattle and non-lactating dairy cows (GCNL). A total of 54 prediction equations available in the literature were evaluated. A total of 96 multiple linear models were developed for predicting CH4 production (MJ/day). The predictor variables were DM intake (DMI), gross energy (GE) intake, BW, DMI as proportion of BW, NDF concentration, ether extract (EE) concentration, dietary proportion of concentrate and GE digestibility. Model selection criteria were significance (P < 0.05) and variance inflation factor lower than three for all predictors. Each model performance was evaluated by leave-one-out cross-validation. The Intergovernmental Panel on Climate Change (2006) Tier 2 method performed better for GEN and GCNL than LAC and overpredicted CH4 production for all datasets. Increasing complexity of the newly developed models resulted in greater performance. The GCNL had a greater number of equations with expanded possibilities to correct for diet characteristics such as EE and NDF concentrations and dietary proportion of concentrate. For the LAC dataset, equations based on intake and animal characteristics were developed. The equations developed in the present study can be useful for accurate and precise estimation of CH4 emissions from cattle in tropical conditions. These equations could improve accuracy of greenhouse gas inventories for tropical countries. The results provide a better understanding of the dietary and animal characteristics that influence the production of enteric CH4 in tropical production systems.
Dietary L-arginine supplementation increased mammary gland vascularity of lactating sows
- D. M. Holanda, C. S. Marcolla, S. E. F. Guimarães, M. M. Neves, G. J. Hausman, M. S. Duarte, M. L. T. Abreu, A. Saraiva
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The present study aimed to evaluate the mechanisms modulated by dietary arginine supplementation to sows during lactation regarding antioxidant capacity and vascularization of mammary glands. At 109 days of gestation, animals were transferred to individual farrowing crates equipped with manual feeders and automatic drinker bowls. Environmental temperature and humidity inside the farrowing rooms were registered every 15 min. At farrowing, sows were assigned in a completely randomized design to a control diet (CON) or the CON diet supplemented with 1.0% L-arginine (ARG). A total of three gilts and two sows were fed the CON diet, whereas three gilts and three sows were fed ARG diets. Sows were fed a fixed amount of 6.0 kg/day, subdivided equally in four delivery times (0700, 1000, 1300 and 1600 h) for 21 days. At weaning, sows were slaughtered and mammary tissue samples and blood from the pudendal vein were collected. Data were analyzed considering each sow as an experimental unit. Differences were considered at P<0.05. L-arginine fed sows presented lower messenger RNA (mRNA) expression for prolactin receptor (P=0.002), angiopoietin1 (P=0.03) and receptor tyrosine kinase (P=0.01); higher mRNA expression for prostaglandin synthase 1 (P=0.01); a trend of decrease for glucocorticoid receptor (P=0.06) and IGF receptor 1 (P=0.07); and a trend (P=0.05) for an increased glutathione peroxidase mRNA expression. The angiopoietin2:angiopoietin1 mRNA ratio tended to increase (P=0.07) in ARG fed sows. L-arginine fed sows had greater (P=0.04) volumetric proportion of blood vessels and a trend of enhance (P=0.07) in the number of blood vessels per mm2. These findings show that 1.0% ARG supplementation to sows activates proliferative mechanisms, may improve mammary tissues’ angiogenesis and tended to increase mRNA expression of genes that encode antioxidant enzymes in mammary gland of sows.
Review: Animal model and the current understanding of molecule dynamics of adipogenesis
- C. F. Campos, M. S. Duarte, S. E. F. Guimarães, L. L. Verardo, S. Wei, M. Du, Z. Jiang, W. G. Bergen, G. J. Hausman, M. Fernyhough-Culver, E. Albrecht, M. V. Dodson
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Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.
Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study
- R. G. Karam, V. Breda, F. A. Picon, D. L. Rovaris, M. M. Victor, C. A. I. Salgado, E. S. Vitola, K. L. Silva, P. O. Guimarães-da-Silva, N. R. Mota, A. Caye, P. Belmonte-de-Abreu, L. A. Rohde, E. H. Grevet, C. H. D. Bau
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- Journal:
- Psychological Medicine / Volume 45 / Issue 10 / July 2015
- Published online by Cambridge University Press:
- 23 January 2015, pp. 2045-2056
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Background
Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.
MethodA 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.
ResultsRetention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).
ConclusionsDespite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.
Effect of heat stress and feeding phosphorus levels on pig electron transport chain gene expression
- M. M. D. C. A. Weller, L. Alebrante, P. H. R. F. Campos, A. Saraiva, B. A. N. Silva, J. L. Donzele, R. F. M. Oliveira, F. F. Silva, E. Gasparino, P. S. Lopes, S. E. F. Guimarães
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The purpose of this study was to evaluate the effect of temperature and different levels of available phosphorus (aP) on the expression of nine genes encoding electron transport chain proteins in the Longissimus dorsi (LD) muscle of pigs. Two trials were carried out using 48 high-lean growth pigs from two different growth phases: from 15 to 30 kg (phase 1) and from 30 to 60 kg (phase 2). Pigs from growth phase 1 were fed with three different levels of dietary aP (0.107%, 0.321% or 0.535%) and submitted either to a thermoneutral (24°C and RH at 76%) or to a heat stress (34°C and RH at 70%) environment. Pigs from growth phase 2 were fed with three different levels of dietary aP (0.116%, 0.306% or 0.496%) and submitted either to a thermoneutral (22ºC and RH at 77%) or to a heat stress (32ºC and RH at 73%) environment. Heat stress decreased (P<0.001) average daily feed intake at both growth phases. At 24°C, pigs in phase 1 fed the 0.321% aP diet had greater average daily gain and feed conversion (P<0.05) than those fed the 0.107% or 0.535% while, at 34°C pigs fed the 0.535% aP had the best performance (P<0.05). Pigs from phase 2 fed the 0.306% aP had best performance in both thermal environments. Gene expression profile was analyzed by quantitative real-time polymerase chain reaction. Irrespective of growing phase, the expression of six genes was lower (P<0.05) at high temperature than at thermoneutrality. The lower expression of these genes under high temperatures evidences the effects of heat stress by decreasing oxidative metabolism, through adaptive physiological mechanisms in order to reduce heat production. In pigs from phase 1, six genes were differentially expressed across aP levels (P<0.05) in the thermoneutral and one gene in the heat stress. In pigs from phase 2, two genes were differentially expressed across aP levels (P<0.05) in both thermal environments. These data revealed strong evidence that phosphorus and thermal environments are key factors to regulate oxidative phosphorylation with direct implications on animal performance.
Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade
- H.-J. BANDELT, J. ALVES-SILVA, P. E. M. GUIMARÃES, M. S. SANTOS, A. BREHM, L. PEREIRA, A. COPPA, J. M. LARRUGA, C. RENGO, R. SCOZZARI, A. TORRONI, M. J. PRATA, A. AMORIM, V. F. PRADO, S. D. J. PENA
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- Journal:
- Annals of Human Genetics / Volume 65 / Issue 6 / November 2001
- Published online by Cambridge University Press:
- 15 February 2002, pp. 549-563
- Print publication:
- November 2001
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The mtDNA haplogroup L3e, which is identified by the restriction site +2349 MboI within the Afro-Eurasian superhaplogroup L3 (−3592 HpaI), is omnipresent in Africa but virtually absent in Eurasia (except for neighbouring areas with limited genetic exchange). L3e was hitherto poorly characterised in terms of HVS-I motifs, as the ancestral HVS-I type of L3e cannot be distinguished from the putative HVS-I ancestor of the entire L3 (differing from the CRS by a transition at np 16223). An MboI screening at np 2349 of a large number of Brazilian and Caribbean mtDNAs (encompassing numerous mtDNAs of African ancestry), now reveals that L3e is subdivided into four principal clades, each characterised by a single mutation in HVS-I, with additional support coming from HVS-II and partial RFLP analysis. The apparently oldest of these clades (transition at np 16327) occurs mainly in central Africa and was probably carried to southern Africa with the Bantu expansion(s). The most frequent clade (transition at np 16320) testifies to a pronounced expansion event in the mid-Holocene and seems to be prominent in many Bantu groups from all of Africa. In contrast, one clade (transition at np 16264) is essentially restricted to Atlantic western Africa (including Cabo Verde). We propose a tentative L3e phylogeny that is based on 197 HVS-I sequences. We conclude that haplogroup L3e originated in central or eastern Africa about 46,000 (±14,000) years ago, and was a hitchhiker of much later dispersal and local expansion events, with the rise of food production and iron smelting. Enforced migration of African slaves to the Americas translocated L3e mitochondria, the descendants of which in Brazil and the Caribbean still reflect their different regional African ancestries.