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1.
Proc Natl Acad Sci U S A ; 120(15): e2213987120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37011196

RESUMO

The dinosaur-bird transition involved several anatomical, biomechanical, and physiological modifications of the theropod bauplan. Non-avian maniraptoran theropods, such as Troodon, are key to better understand changes in thermophysiology and reproduction occurring during this transition. Here, we applied dual clumped isotope (Δ47 and Δ48) thermometry, a technique that resolves mineralization temperature and other nonthermal information recorded in carbonates, to eggshells from Troodon, modern reptiles, and modern birds. Troodon eggshells show variable temperatures, namely 42 and 29 ± 2 °C, supporting the hypothesis of an endothermic thermophysiology with a heterothermic strategy for this extinct taxon. Dual clumped isotope data also reveal physiological differences in the reproductive systems between Troodon, reptiles, and birds. Troodon and modern reptiles mineralize their eggshells indistinguishable from dual clumped isotope equilibrium, while birds precipitate eggshells characterized by a positive disequilibrium offset in Δ48. Analyses of inorganic calcites suggest that the observed disequilibrium pattern in birds is linked to an amorphous calcium carbonate (ACC) precursor, a carbonate phase known to accelerate eggshell formation in birds. Lack of disequilibrium patterns in reptile and Troodon eggshells implies these vertebrates had not acquired the fast, ACC-based eggshell calcification process characteristic of birds. Observation that Troodon retained a slow reptile-like calcification suggests that it possessed two functional ovaries and was limited in the number of eggs it could produce; thus its large clutches would have been laid by several females. Dual clumped isotope analysis of eggshells of extinct vertebrates sheds light on physiological information otherwise inaccessible in the fossil record.


Assuntos
Casca de Ovo , Répteis , Animais , Feminino , Carbonato de Cálcio , Isótopos
2.
J Clin Psychopharmacol ; 44(2): 133-140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38421922

RESUMO

PURPOSE/BACKGROUND: Anxiety symptoms in major depressive disorder (MDD) are frequent, and they decrease response to antidepressant treatment (ADT), and affect patient functioning. This post hoc analysis examined the efficacy of adjunctive brexpiprazole on individual depressive symptoms and functioning in patients with MDD with anxious distress. METHODS/PROCEDURES: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (ClinicalTrials.gov identifiers: NCT01360645, NCT01360632, NCT02196506). Patients were stratified using proxy criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, anxious distress. Changes in Montgomery-Åsberg Depression Rating Scale item scores and Sheehan Disability Scale mean score from baseline to week 6 were determined for ADT + brexpiprazole (2 and 2-3 mg) versus ADT + placebo. FINDINGS/RESULTS: At baseline, 450 of 746 patients (60.3%, 2 mg analysis) and 670 of 1162 patients (57.7%, 2-3 mg analysis) had anxious distress. In patients with anxious distress, ADT + brexpiprazole 2 mg or 2 to 3 mg showed greater improvements than ADT + placebo (P < 0.05) on the Montgomery-Åsberg Depression Rating Scale items of apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, lassitude, inability to feel, and pessimistic thoughts (Cohen d effect sizes, 0.18-0.44), and on Sheehan Disability Scale mean score (effect sizes, 0.21-0.23). IMPLICATIONS/CONCLUSIONS: Adjunctive brexpiprazole is efficacious in reducing core depressive symptoms, sleep, and appetite, as well as improving functioning, in patients with MDD and anxious distress who have inadequate response to ADTs.


Assuntos
Transtorno Depressivo Maior , Quinolonas , Tiofenos , Humanos , Antidepressivos , Ansiedade/tratamento farmacológico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Can J Psychiatry ; 69(7): 513-523, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38425284

RESUMO

OBJECTIVES: To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. METHODS: An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1-2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5-2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. RESULTS: Of 122 enrolled patients, 120 (98.4%) were treated (mean [SD] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [SD]: 16.1 [4.7]; change [95% confidence interval]: -8.11 [-9.34, -6.88]; p < 0.001) and IDS-SR total score (baseline mean [SD]: 41.3 [9.8]; change [95% confidence interval]: -17.38 [-20.08, -14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue (n = 13, 10.8%), headache (n = 13, 10.8%), insomnia (n = 12, 10.0%), nausea (n = 9, 7.5%), tremor (n = 8, 6.7%), and weight increase (n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean (SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. CONCLUSIONS: Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04830215.


Assuntos
Antidepressivos , Transtorno Depressivo Maior , Medidas de Resultados Relatados pelo Paciente , Quinolonas , Tiofenos , Humanos , Masculino , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Adulto , Pessoa de Meia-Idade , Canadá , Antidepressivos/efeitos adversos , Antidepressivos/administração & dosagem , Quinolonas/efeitos adversos , Quinolonas/administração & dosagem , Quinolonas/farmacologia , Tiofenos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/farmacologia , Quimioterapia Combinada
4.
BMC Psychiatry ; 23(1): 162, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918846

RESUMO

BACKGROUND: Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada. METHODS: Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression - Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population. RESULTS: Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration. CONCLUSIONS: AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms. TRIAL REGISTRATION: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Masculino , Feminino , Aripiprazol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , Escalas de Graduação Psiquiátrica Breve , Antipsicóticos/uso terapêutico , Resultado do Tratamento
5.
BMC Psychiatry ; 23(1): 383, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259053

RESUMO

BACKGROUND: Functional impairment affects many patients with schizophrenia. Treatment with the long-acting injectable antipsychotic aripiprazole once-monthly (AOM) may help improve functioning. OBJECTIVES: To explore changes in functioning in patients with schizophrenia who received AOM treatment in observational studies. METHODS: Here we report functional outcomes in the form of Global Assessment of Functioning (GAF) scores in a pooled analysis of data from two observational studies from Canada (NCT02131415) and Germany (vfa non-interventional studies registry 15960N). Data from 396 patients were analyzed. RESULTS: At baseline, the mean GAF score was 47.7 (SD 13.4). During 6 months of treatment with AOM, the mean GAF score increased to 59.4 (SD 15.8). Subgroups stratified by patient age (≤35 years/>35 years), sex, disease duration (≤5 years/>5 years) and disease severity at baseline had all significantly improved their GAF at month 6. 51.5% of the patients showed a GAF score increase of at least 10 points, which was regarded as clinically meaningful, and were considered responders. CONCLUSIONS: These data show that treatment with AOM may help improve patient functioning in a routine treatment setting. TRIAL REGISTRATION: NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.


Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Humanos , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Canadá , Preparações de Ação Retardada/uso terapêutico , Gravidade do Paciente , Esquizofrenia/tratamento farmacológico , Masculino , Feminino
6.
BMC Psychiatry ; 22(1): 773, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482352

RESUMO

BACKGROUND: ReLiAM, Real-Life Assessment of Abilify Maintena, was the first reported long-term prospective non-interventional study for patients with schizophrenia treated with aripiprazole once-monthly injectable formulation (AOM) under real-life conditions. ReLiAM's primary aim was to evaluate the evolution of global functional status in patients treated with AOM for 12 months in Canada. METHODS: The objective of this post hoc analysis of the ReLiAM study is to investigate the treatment effects of real-life use of AOM over a 1-year period in the subgroup of patients with reported substance use compared with patients without substance use. RESULTS: The results of this post hoc analysis demonstrate that treatment with AOM for 12 months in patients with schizophrenia was comparably effective in improving global functioning in subgroups of patients with and without concomitant substance use. CONCLUSIONS: These results support the use of AOM for the treatment of schizophrenia in patients with or without concomitant substance use. TRIAL REGISTRATION: ClinicalTrials.gov NCT02131415, first posted on May 6, 2014. Overall trial status: Terminated.


Assuntos
Esquizofrenia , Transtornos Relacionados ao Uso de Substâncias , Humanos , Aripiprazol/uso terapêutico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Estudos Prospectivos , Canadá
7.
J Exp Biol ; 219(Pt 23): 3738-3749, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27634400

RESUMO

Mandibular force profiles apply the principles of beam theory to identify mandibular biomechanical properties that reflect the bite force and feeding strategies of extant and extinct predators. While this method uses the external dimensions of the mandibular corpus to determine its biomechanical properties, more accurate results could potentially be obtained by quantifying its internal cortical bone distribution. To test this possibility, mandibular force profiles were calculated using both external mandibular dimensions ('solid mandible model') and quantification of internal bone distribution of the mandibular corpus obtained from computed tomography scans ('hollow mandible model') for five carnivorans (Canis lupus, Crocuta crocuta, Panthera leo, Neofelis nebulosa and the extinct Canis dirus). Comparison reveals that the solid model slightly overestimates mandibular biomechanical properties, but the pattern of change in biomechanical properties along the mandible remains the same. As such, feeding behavior reconstructions are consistent between the two models and are not improved by computed tomography. Bite force estimates produced by the two models are similar, except in C. crocuta, where the solid model underestimates bite force by 10-14%. This discrepancy is due to the more solid nature of the C. crocuta mandible relative to other carnivorans. Therefore, computed tomography improves bite force estimation accuracy for taxa with thicker mandibular corpora, but not significantly so otherwise. Bite force estimates derived from mandibular force profiles are far closer to empirically measured bite force than those inferred from jaw musculature dimension. Consequently, bite force estimates derived from this method can be used to calibrate finite-element analysis models.


Assuntos
Fenômenos Biomecânicos/fisiologia , Força de Mordida , Carnívoros/fisiologia , Comportamento Alimentar/fisiologia , Hyaenidae/fisiologia , Mandíbula/fisiologia , Panthera/fisiologia , Lobos/fisiologia , Animais , Análise de Elementos Finitos , Modelos Biológicos , Comportamento Predatório , Estresse Mecânico
8.
Anat Rec (Hoboken) ; 306(7): 1669-1696, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35815600

RESUMO

Counts of the number of skeletal specimens of "adult" megaherbivores and large theropods from the Morrison and Dinosaur Park formations-if not biased by taphonomic artifacts-suggest that the big meat-eaters were more abundant, relative to the number of big plant-eaters, than one would expect on the basis of the relative abundance of large carnivores and herbivores in modern mammalian faunas. Models of megaherbivore population density (number of individuals per square kilometer) that attempt to take into account ecosystem productivity, the size structure of megaherbivore populations, and individual megaherbivore energy requirements, when combined with values of the large theropod/megaherbivore abundance ratio, suggest that large theropods may have been more abundant on the landscape than estimates extrapolated from the population density versus body mass relationship of mammalian carnivores. Models of the meat production of megaherbivore populations and the meat requirements of "adult" large theropods suggest that herbivore productivity would have been insufficient to support the associated number of individuals of "adult" large theropods, unless the herbivore production/biomass ratio was substantially higher, and/or the large theropod meat requirement markedly lower, than expectations based on modern mammals. Alternatively, or in addition to one or both of these other factors, large theropods likely included dinosaurs other than megaherbivores as significant components of their diet.


Assuntos
Carnivoridade , Dinossauros , Cadeia Alimentar , Modelos Biológicos , Animais , Canadá , Dinossauros/anatomia & histologia , Dinossauros/fisiologia , Carne , Densidade Demográfica , Estados Unidos
9.
J Psychiatr Res ; 162: 71-78, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37099968

RESUMO

BACKGROUND: Patient-reported outcomes can capture domains that are meaningful to patients, such as life engagement in major depressive disorder (MDD), which reflects life fulfillment, well-being, and participation in valued and meaningful activities. This analysis investigated the effects of brexpiprazole adjunct to antidepressant treatment (ADT) on patient life engagement over the short and long term, using the 10-item Inventory of Depressive Symptomatology Self-Report (IDS-SR10) Life Engagement subscale. METHODS: Short-term data were pooled from three 6-week, randomized, double-blind studies of ADT + brexpiprazole 2-3 mg/day versus ADT + placebo in adult outpatients with MDD (DSM-IV-TR criteria) and inadequate response to ADTs. Long-term data were from a 26-52-week, open-label extension study of ADT + brexpiprazole 0.5-3 mg/day. RESULTS: Over 6 weeks, ADT + brexpiprazole (n = 579) showed greater improvement in IDS-SR10 Life Engagement subscale score than ADT + placebo (n = 583), with a least squares mean difference of -1.19 (95% confidence limits: -1.78, -0.59; p = 0.0001; Cohen's d effect size: 0.23). Greater improvement for ADT + brexpiprazole versus ADT + placebo (p < 0.05) was also observed on eight life engagement items, with effect sizes ranging from 0.12 to 0.24. In the long-term study, mean (standard deviation) IDS-SR10 Life Engagement subscale score changed by -2.4 (4.9) points to Week 26 (n = 2047), and -3.7 (5.3) points to Week 52 (n = 768), with mean improvements on all ten items. CONCLUSIONS: Beyond its efficacy on depressive symptoms, adjunctive brexpiprazole may improve patient life engagement, thereby helping patients with MDD to achieve personally meaningful functional outcomes.


Assuntos
Transtorno Depressivo Maior , Adulto , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Autorrelato , Resultado do Tratamento , Quimioterapia Combinada , Antidepressivos/farmacologia , Método Duplo-Cego
10.
Sci Adv ; 9(49): eadi0505, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064561

RESUMO

Tyrannosaurids were large carnivorous dinosaurs that underwent major changes in skull robusticity and body proportions as they grew, suggesting that they occupied different ecological niches during their life span. Although adults commonly fed on dinosaurian megaherbivores, the diet of juvenile tyrannosaurids is largely unknown. Here, we describe a remarkable specimen of a juvenile Gorgosaurus libratus that preserves the articulated hindlimbs of two yearling caenagnathid dinosaurs inside its abdominal cavity. The prey were selectively dismembered and consumed in two separate feeding events. This predator-prey association provides direct evidence of an ontogenetic dietary shift in tyrannosaurids. Juvenile individuals may have hunted small and young dinosaurs until they reached a size when, to satisfy energy requirements, they transitioned to feeding on dinosaurian megaherbivores. Tyrannosaurids occupied both mesopredator and apex predator roles during their life span, a factor that may have been key to their evolutionary success.


Assuntos
Dinossauros , Fósseis , Humanos , Animais , Conteúdo Gastrointestinal , Evolução Biológica , Crânio/anatomia & histologia , Dieta , Dinossauros/anatomia & histologia
11.
Eur Psychiatry ; 65(1): e42, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35855645

RESUMO

BACKGROUND: Noninterventional naturalistic studies are an important complement to randomized controlled trials. Aripiprazole once-monthly (AOM) is an atypical antipsychotic in a long-acting injectable formulation. METHODS: A pooled analysis of two noninterventional studies was undertaken to validate previous results on AOM effectiveness and safety in a larger population and improve statistical power for preplanned subgroup analyses. We analyzed data from 409 patients with schizophrenia who were treated with AOM and were enrolled in noninterventional studies in Germany (via noninterventional studies registry 15,960 N) and Canada (NCT02131415). Data collected at baseline, 3 and 6 months were analyzed. Among the endpoints were psychopathology (brief psychiatric rating scale [BPRS]) and disease severity (clinical global impression [CGI]). RESULTS: Mean patient age was 38.9 (SD 14.8) years, and 59.9% were male. BPRS decreased from 48.1 (SD 15.6) at baseline to 36.5 (SD 13.7) at month 6 (p < 0.001). CGI decreased from 4.47 (SD 0.90) at baseline to 3.64 (SD 1.16) at month 6 (p < 0.001). A total of 54.4% were responders (at least 20% reduction) on the BPRS, and 56.5% had a CGI-S-score that was at least 1 level better than baseline. A total of 43.4% were considered responders on both the BPRS and CGI scales. A total of 45.2% were considered in remission. Adverse events were rare and corresponded to the previously known safety profile of AOM. CONCLUSIONS: Treatment with AOM for patients with schizophrenia appeared effective and safe under real-life conditions.


Assuntos
Antipsicóticos , Aripiprazol , Esquizofrenia , Adulto , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Escalas de Graduação Psiquiátrica Breve , Canadá , Estudos Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento
12.
J Patient Rep Outcomes ; 6(1): 111, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224450

RESUMO

BACKGROUND: Patient-reported outcomes can measure health aspects that are meaningful to patients, such as 'life engagement' in major depressive disorder (MDD). Expert psychiatrists recently identified ten items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) that can be used to measure patient life engagement. This study aimed to explore the concept of patient life engagement and provide support for the IDS-SR10 Life Engagement subscale from the patient perspective. METHODS: Semi-structured video interviews were conducted with adults with MDD in the United States. Patients were asked if they ever felt engaged with life, and how this affected their feelings, activities, socializing, and thoughts. Then, patients discussed the ten expert-selected IDS-SR items, and rated the relevance of all 30 items to patient life engagement on a 4-point scale. RESULTS: Patients (N = 20) understood the 'engaged with life' concept and could provide examples from their own lives, such as increased energy/motivation (100%), being more social/spending time with others (85%), being more communicative (80%), and having better mood (75%). Nineteen patients (95%) indicated that all ten IDS-SR10 Life Engagement items were relevant to patient life engagement, and nine of the ten items had a mean score ≥ 3 (moderately relevant). Four additional items (all relating to mood) also scored ≥ 3. CONCLUSIONS: Patients found the concept of life engagement to be important and relatable, and confirmed the IDS-SR10 captures the defining non-mood-related aspects of patient life engagement. This research supports the relevance of patient life engagement as a potential clinical outcome beyond core mood symptoms, and the use of the IDS-SR10 Life Engagement subscale in patient-oriented research.

13.
J Affect Disord ; 316: 201-208, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35970327

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a clinically heterogenous condition and its treatment should be individualized according to the presence of particular symptom clusters. The aim of this pooled analysis was to investigate the effects of adjunctive brexpiprazole on different symptom clusters in MDD. METHODS: Data were included from four similarly designed, short-term, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in adults with MDD and inadequate response to 2-4 antidepressant treatments (ADTs), including 1 administered by investigators. Mean changes from baseline and Cohen's d effect sizes (ES) versus placebo were determined for the following Montgomery-Åsberg Depression Rating Scale symptom clusters: core, anhedonia, dysphoria, retardation, vegetative, loss of interest, and lassitude. RESULTS: Over 6 weeks, ADT + brexpiprazole 2 mg (n = 486) showed greater improvement than ADT + placebo (n = 585) for all symptom clusters: core (ES = 0.36; p < 0.0001), anhedonia (ES = 0.43; p < 0.0001), dysphoria (ES = 0.27; p < 0.0001), retardation (ES = 0.32; p < 0.0001), vegetative (ES = 0.29; p < 0.0001), loss of interest (ES = 0.30; p < 0.0001), and lassitude (ES = 0.33; p < 0.0001). Improvements of similar magnitude were observed for ADT + brexpiprazole 2-3 mg (n = 770) versus ADT + placebo (n = 788) (ES = 0.24-0.38; all clusters p < 0.0001). In most cases, improvement over ADT + placebo was observed from Week 1 onwards. LIMITATIONS: Post hoc analysis with no adjunctive active comparator. CONCLUSIONS: Patients receiving adjunctive brexpiprazole versus adjunctive placebo showed improvements across a range of MDD symptom clusters. Improvements appeared early (generally from Week 1) and were maintained over 6 weeks. These data indicate that adjunctive brexpiprazole may benefit multiple subtypes of patient with MDD and inadequate response to ADTs.


Assuntos
Transtorno Depressivo Maior , Adulto , Anedonia , Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Fadiga/tratamento farmacológico , Humanos , Quinolonas , Síndrome , Tiofenos , Resultado do Tratamento
14.
J Clin Psychiatry ; 83(2)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235720

RESUMO

Objective: To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia.Methods: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia (DSM-IV-TR criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies). Functioning was measured using the Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF) scales, with response defined as a PSP/GAF increase of ≥ 10 points and remission as PSP score ≥ 71 or GAF score ≥ 61.Results: Patients receiving brexpiprazole (n = 831) showed greater improvement than those receiving placebo (n = 490) from baseline to week 6 in PSP score (least squares mean difference, 3.20; 95% confidence interval, 1.82-4.58; P < .0001; Cohen d = 0.31) and in all 4 PSP domains. At week 52 of the maintenance study (which had a low completion rate primarily due to the early termination), GAF functional remission was achieved by 65.3% (62/95) of stabilized patients randomized to brexpiprazole and 47.1% (48/102) of stabilized patients randomized to placebo, with a number needed to treat of 6 (95% confidence interval, 4-22; P = .0076). At week 52 of the open-label studies (n = 177), PSP functional response and remission were achieved by 84.2% and 41.8% of patients receiving brexpiprazole, respectively.Conclusions: Although limited by the lack of an active comparator, analyses of this large dataset demonstrate that brexpiprazole treatment is associated with clinically relevant improvement in functioning among patients with schizophrenia, in the short term and long term.Trial Registration: Data used in this post hoc analysis were from studies with ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, and NCT01810783.


Assuntos
Antipsicóticos , Quinolonas , Esquizofrenia , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Humanos , Quinolonas/efeitos adversos , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Tiofenos/efeitos adversos , Resultado do Tratamento
15.
Proc Biol Sci ; 278(1725): 3625-34, 2011 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-21490022

RESUMO

Little is known about the olfactory capabilities of extinct basal (non-neornithine) birds or the evolutionary changes in olfaction that occurred from non-avian theropods through modern birds. Although modern birds are known to have diverse olfactory capabilities, olfaction is generally considered to have declined during avian evolution as visual and vestibular sensory enhancements occurred in association with flight. To test the hypothesis that olfaction diminished through avian evolution, we assessed relative olfactory bulb size, here used as a neuroanatomical proxy for olfactory capabilities, in 157 species of non-avian theropods, fossil birds and living birds. We show that relative olfactory bulb size increased during non-avian maniraptoriform evolution, remained stable across the non-avian theropod/bird transition, and increased during basal bird and early neornithine evolution. From early neornithines through a major part of neornithine evolution, the relative size of the olfactory bulbs remained stable before decreasing in derived neoavian clades. Our results show that, rather than decreasing, the importance of olfaction actually increased during early bird evolution, representing a previously unrecognized sensory enhancement. The relatively larger olfactory bulbs of earliest neornithines, compared with those of basal birds, may have endowed neornithines with improved olfaction for more effective foraging or navigation skills, which in turn may have been a factor allowing them to survive the end-Cretaceous mass extinction.


Assuntos
Evolução Biológica , Aves/fisiologia , Dinossauros/fisiologia , Bulbo Olfatório/anatomia & histologia , Olfato , Animais , Aves/anatomia & histologia , Dinossauros/anatomia & histologia
16.
Sci Adv ; 6(7): eaax9361, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32110726

RESUMO

Studying the origin of avian thermoregulation is complicated by a lack of reliable methods for measuring body temperatures in extinct dinosaurs. Evidence from bone histology and stableisotopes often relies on uncertain assumptions about the relationship between growth rate and body temperature, or the isotopic composition (δ18O) of body water. Clumped isotope (Δ47) paleothermometry, based on binding of 13C to 18O, provides a more robust tool, but has yet to be applied across a broad phylogenetic range of dinosaurs while accounting for paleoenvironmental conditions. Applying this method to well-preserved fossil eggshells demonstrates that the three major clades of dinosaurs, Ornithischia, Sauropodomorpha, and Theropoda, were characterized by warm body temperatures. Dwarf titanosaurs may have exhibited similar body temperatures to larger sauropods, although this conclusion isprovisional, given current uncertainties in taxonomic assignment of dwarf titanosaur eggshell. Our results nevertheless reveal that metabolically controlled thermoregulation was the ancestral condition for Dinosauria.


Assuntos
Regulação da Temperatura Corporal , Dinossauros/metabolismo , Casca de Ovo/química , Animais , Peso Corporal , Calibragem , Carbonatos/análise , Fósseis , Isótopos , Moluscos/química , Filogenia , Temperatura , Oligoelementos/análise
17.
Proc Biol Sci ; 276(1657): 667-73, 2009 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-18957367

RESUMO

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.


Assuntos
Evolução Biológica , Dinossauros/fisiologia , Olfato/fisiologia , Jacarés e Crocodilos/anatomia & histologia , Jacarés e Crocodilos/fisiologia , Animais , Dinossauros/anatomia & histologia , Extinção Biológica , Mamíferos/anatomia & histologia , Mamíferos/fisiologia , Bulbo Olfatório/anatomia & histologia , Bulbo Olfatório/fisiologia , Filogenia , Análise de Regressão
18.
Sci Rep ; 9(1): 17801, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31780682

RESUMO

Daspletosaurus is a large tyrannosaurine found in upper Campanian deposits of Alberta and Montana. Although several large subadult and adult individuals of this taxon are known, only one juvenile individual, TMP 1994.143.1, has been identified. This specimen has played a key role in the idea that juvenile tyrannosaurid individuals are difficult to differentiate among species. Here the taxonomic affinity of TMP 1994.143.1 is reassessed in light of a juvenile tyrannosaurine postorbital recently discovered in the Dinosaur Park Formation of Alberta. Anatomical comparisons and phylogenetic analyses reveal that TMP 1994.143.1 is referable to the albertosaurine Gorgosaurus libratus, whereas the new postorbital belongs to a small juvenile Daspletosaurus. This taxonomic reassignment of TMP 1994.143.1 results in the juvenile ontogenetic stage of Daspletosaurus being known only from two isolated cranial elements. The new postorbital provides insights into early Daspletosaurus ontogeny, revealing that the cornual process developed earlier or faster than in other tyrannosaurids. Although some ontogenetic changes in the postorbital are found to be unique to Daspletosaurus, overall changes are most consistent with those of other large tyrannosaurines. Our results also show that diagnostic features develop early in ontogeny, such that juveniles of different tyrannosaurid species are easier to differentiate than previously thought.


Assuntos
Anatomia Comparada/métodos , Dinossauros/anatomia & histologia , Dinossauros/classificação , Alberta , Animais , Dinossauros/genética , Fósseis/anatomia & histologia , Montana , Paleontologia/métodos , Filogenia , Crânio/anatomia & histologia
19.
Sci Rep ; 8(1): 3170, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29545620

RESUMO

Dinosaurs thrived and reproduced in various regions worldwide, including the Arctic. In order to understand their nesting in diverse or extreme environments, the relationships between nests, nesting environments, and incubation methods in extant archosaurs were investigated. Statistical analyses reveal that species of extant covered nesters (i.e., crocodylians and megapodes) preferentially select specific sediments/substrates as a function of their nesting style and incubation heat sources. Relationships between dinosaur eggs and the sediments in which they occur reveal that hadrosaurs and some sauropods (i.e., megaloolithid eggs) built organic-rich mound nests that relied on microbial decay for incubation, whereas other sauropods (i.e., faveoloolithid eggs) built sandy in-filled hole nests that relied on solar or potentially geothermal heat for incubation. Paleogeographic distribution of mound nests and sandy in-filled hole nests in dinosaurs reveals these nest types produced sufficient incubation heat to be successful up to mid latitudes (≤47°), 10° higher than covered nesters today. However, only mound nesting and likely brooding could have produced sufficient incubation heat for nesting above the polar circle (>66°). As a result, differences in nesting styles may have placed restrictions on the reproduction of dinosaurs and their dispersal at high latitudes.


Assuntos
Comportamento de Nidação , Animais , Regiões Árticas , Comportamento Animal , Dinossauros , Ecossistema , Meio Ambiente , Ambientes Extremos , Feminino , Fósseis , História Antiga , Óvulo/metabolismo , Paleografia , Reprodução
20.
PLoS One ; 10(11): e0142829, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26605799

RESUMO

Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests with fully exposed eggs only became widespread among Euornithes. A potential co-evolution of open nests and brooding behavior among maniraptorans may have freed theropods from the ground-based restrictions inherent to covered nests and allowed the exploitation of alternate nesting locations. These changes in nesting styles and behaviors thus may have played a role in the evolutionary success of maniraptorans (including birds).


Assuntos
Evolução Biológica , Aves/classificação , Dinossauros/classificação , Casca de Ovo/anatomia & histologia , Comportamento de Nidação/fisiologia , Filogenia , Animais , Aves/fisiologia , Difusão , Dinossauros/fisiologia , Análise Discriminante , Casca de Ovo/fisiologia , Feminino , Fósseis , Masculino , Porosidade , Reprodução/fisiologia , Água , Zigoto/classificação , Zigoto/fisiologia
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