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1.
J Clin Psychol ; 77(1): 254-267, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32662088

RESUMO

OBJECTIVE: Emotional or psychological pain is a core symptom of complicated grief (CG), yet its correlates are largely unexamined among bereaved individuals. METHOD: Bereaved adults (N = 135) completed self-reports regarding psychological pain, CG, depression, and suicidality. We assessed correlations among these variables and tested whether psychological pain was elevated among individuals with CG and individuals with current or past suicidal thoughts and behaviors. Using logistic regression, we also assessed psychological pain, depression, and CG symptom severity as predictors of suicide risk. RESULTS: Psychological pain was strongly associated with both CG and depression severity and was elevated among subjects reporting current or past suicidality. CG and depression were not statistically significant predictors of suicidal ideation after accounting for the effects of psychological pain. CONCLUSIONS: Psychological pain is strongly associated with bereavement-related psychopathology and warrants further investigation in studies examining the nature and treatment of CG.


Assuntos
Luto , Suicídio , Adulto , Depressão , Pesar , Humanos , Dor
2.
J Am Anim Hosp Assoc ; 57(6): 278-284, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606579

RESUMO

The study objective was to evaluate sedative, hemodynamic, and echocardiographic effects of cats receiving single-dose, oral gabapentin. A prospective, double-blinded, placebo-controlled, crossover study was conducted with 10 client-owned cats. Vital parameters, physical exam, blood pressure, echocardiography, and sedation scoring were performed at each visit within 2 hr of receiving either a placebo or gabapentin capsule. Vital parameters, blood pressure recordings, and echocardiographic measurements were compared between baseline, gabapentin, and placebo; interobserver agreement for sedation scoring and correlation between variables were also evaluated. Seven of 10 cats exhibited mild sedation within 120 min after receiving gabapentin, and no adverse events occurred. Significant differences were detected with two-dimensional fractional shortening (P = .022), left ventricular internal diameter in systole using M-mode (P = .014), and left atrial volume (P < .0001). Interobserver agreement for sedation scoring was near-perfect (κ = 0.84). No significant correlation was found for gabapentin dosage and sedation score. Single-dose oral gabapentin is well tolerated in healthy cats and produces a modest decrease in several echocardiographic parameters of systolic function; however, all affected variables remained within established reference ranges. These results suggest gabapentin may be an appropriate sedative to administer before echocardiography in cats necessitating mild sedation.


Assuntos
Ecocardiografia , Hipnóticos e Sedativos , Animais , Gatos , Estudos Cross-Over , Ecocardiografia/veterinária , Gabapentina , Hemodinâmica , Estudos Prospectivos
3.
Nanomedicine ; 19: 39-48, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31022465

RESUMO

This work looks to improve the efficacy of Adriamycin (ADR) while mitigating its cardiotoxicity using combinations of micellar resveratrol (R): quercetin (Q) (mRQ) or R: curcumin (C) (mRC) in healthy mice and ovarian cancer xenograft models. Ovarian cancer cells, ES2-Luc, or A2780ADR are inoculated in mice (n =4/group) and sorted into eight cohorts. Mice are treated weekly for 4 weeks with ADR, ADR+mRQ, ADR+mRC, or controls (saline, empty micelles, ADR+EM, mRQ, or mRC). To evaluate the degree of cardioprotection, serum is collected to determine the cardiac Troponin I (cTnI). Cardiac tissue is collected for morphological evaluation and evaluation of creatine kinase levels. Our results indicate that mRQ+ADR is statistically significant in tumor reduction in xenograft models. In healthy mice, the left ventricular ejection fraction and fractional shortening in the ADR treated group is most compromised. Co-administration of mRQ with ADR can reduce ADR dosing through chemosensitization while being cardioprotective.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Curcumina/uso terapêutico , Doxorrubicina/efeitos adversos , Micelas , Neoplasias Ovarianas/tratamento farmacológico , Polímeros/química , Quercetina/uso terapêutico , Resveratrol/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/fisiopatologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Concentração Inibidora 50 , Medições Luminescentes , Camundongos , Neoplasias Ovarianas/diagnóstico por imagem , Quercetina/administração & dosagem , Quercetina/farmacologia , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Volume Sistólico/efeitos dos fármacos , Troponina I/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Trauma Stress ; 29(3): 259-67, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27163435

RESUMO

Previous studies have demonstrated bidirectional associations between posttraumatric stress disorder (PTSD) and romantic relationship dissatisfaction. Most of these studies were focused at the level of the disorder, examining the association between relationship dissatisfaction and having a diagnosis of PTSD or the total of PTSD symptoms endorsed. This disorder-level approach is problematic for trauma theorists who posit symptom-level mechanisms for these effects. In the present study, we examined the prospective, bidirectional associations between PTSD symptom clusters (e.g., reexperiencing) and relationship satisfaction using the data from 101 previously studied individuals who had had a recent motor vehicle accident. We also conducted exploratory analyses examining the prospective, bidirectional associations between individual PTSD symptoms and relationship satisfaction. Participants had completed the PTSD Checklist-Civilian Version and the Relationship Assessment Scale at 4, 10, and 16 weeks after the MVA. We performed time-lagged mixed-effects regressions to examine the effect of lagged relationship satisfaction on PTSD clusters and symptoms, and vice versa. No cluster effects were significant after controlling for a false discovery rate. Relationship satisfaction predicted prospective decreases in reliving the trauma (d = 0.42), emotional numbness (d = 0.46), and irritability (d = 0.49). These findings were consistent with the position that relationship satisfaction affects PTSD through symptom-level mechanisms.


Assuntos
Acidentes de Trânsito/psicologia , Relações Interpessoais , Satisfação Pessoal , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Autorrelato , Índice de Gravidade de Doença
5.
Proc Natl Acad Sci U S A ; 110(32): E2958-66, 2013 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-23861496

RESUMO

The chaperonin proteins GroEL and GroES are cellular nanomachines driven by the hydrolysis of ATP that facilitate the folding of structurally diverse substrate proteins. In response to ligand binding, the subunits of a ring cycle in a concerted manner through a series of allosteric states (T, R, and R″), enabling work to be performed on the substrate protein. Removing two salt bridges that ordinarily break during the allosteric transitions of the WT permitted the structure of GroEL-ADP in the R state to be solved to 2.7 Šresolution. Whereas the equatorial domain displays almost perfect sevenfold symmetry, the apical domains, to which substrate proteins bind, and to a lesser extent, the intermediate domains display a remarkable asymmetry. Freed of intersubunit contacts, the apical domain of each subunit adopts a different conformation, suggesting a flexibility that permits interaction with diverse substrate proteins. This result contrasts with a previous cryo-EM study of a related allosteric ATP-bound state at lower resolution. After artificially imposing sevenfold symmetry it was concluded that a GroEL ring in the R-ATP state existed in six homogeneous but slightly different states. By imposing sevenfold symmetry on each of the subunits of the crystal structure of GroEL-ADP, we showed that the synthetic rings of (X-ray) GroEL-ADP and (cryo-EM) GroEL-ATP are structurally closely related. A deterministic model, the click stop mechanism, that implied temporal transitions between these states was proposed. Here, however, these conformational states are shown to exist as a structurally heterogeneous ensemble within a single ring.


Assuntos
Difosfato de Adenosina/química , Chaperonina 60/química , Conformação Proteica , Estrutura Terciária de Proteína , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Regulação Alostérica , Chaperonina 10/química , Chaperonina 10/metabolismo , Chaperonina 60/genética , Chaperonina 60/metabolismo , Microscopia Crioeletrônica , Cristalografia por Raios X , Hidrólise , Modelos Moleculares , Mutação , Ligação Proteica
6.
Biochim Biophys Acta ; 1834(7): 1292-301, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23523885

RESUMO

The RIO kinases are essential protein factors required for the synthesis of new ribosomes in eukaryotes. Conserved in archaeal organisms as well, RIO kinases are among the most ancient of protein kinases. Their exact molecular mechanisms are under investigation and progress of this research would be significantly improved with the availability of suitable molecular probes that selectively block RIO kinases. RIO kinases contain a canonical eukaryotic protein kinase fold, but also display several unusual structural features that potentially create opportunity for the design of selective inhibitors. In an attempt to identify structural leads to target the RIO kinases, a series of pyridine caffeic acid benzyl amides (CABA) were tested for their ability to inhibit the autophosphorylation activity of Archeaoglobus fulgidus Rio1 (AfRio1). Screening of a small library of CABA molecules resulted in the identification of four compounds that measurably inhibited AfRio1 activity. Additional biochemical characterization of binding and inhibition activity of these compounds demonstrated an ATP competitive inhibition mode, and allowed identification of the functional groups that result in the highest binding affinity. In addition, docking of the compound to the structure of Rio1 and determination of the X-ray crystal structure of a model compound (WP1086) containing the desired functional groups allowed detailed analysis of the interactions between these compounds and the enzyme. Furthermore, the X-ray crystal structure demonstrated that these compounds stabilize an inactive form of the enzyme. Taken together, these results provide an important step in identification of a scaffold for the design of selective molecular probes to study molecular mechanisms of Rio1 kinases in vitro and in vivo. In addition, it provides a rationale for the future design of potent inhibitors with drug-like properties targeting an inactive form of the enzyme. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).


Assuntos
Archaea/enzimologia , Proteínas Arqueais/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Proteínas Arqueais/química , Proteínas Arqueais/metabolismo , Sítios de Ligação , Ligação Competitiva , Domínio Catalítico , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Cinética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Ligação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Terciária de Proteína , Piridinas/química , Piridinas/metabolismo , Piridinas/farmacologia , Espectrometria de Massas por Ionização por Electrospray
7.
J Nerv Ment Dis ; 202(8): 620-2, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25075646

RESUMO

Complicated grief (CG) is a bereavement-specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (AS; i.e., the fear of anxiety-related sensations) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms.


Assuntos
Ansiedade/diagnóstico , Ansiedade/psicologia , Pesar , Adulto , Luto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Am Coll Health ; : 1-8, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227928

RESUMO

Objective: This manuscript describes an evidence-based, student-led, single-session group intervention to support emotional wellbeing among graduate students. The present objective is to provide a roadmap for other universities. Participants: Key participants include clinical psychology graduate students (leader and workshop facilitators), faculty supervisor, representatives from receiving departments or schools, and institutional advocates. Methods: The two-hour workshop was based on four core transdiagnostic cognitive behavioral skills, including psychoeducation about emotions, mindful emotional awareness, cognitive flexibility, and behavior change. The workshop was designed and continues to be led by trained graduate students. Results: Key steps and lessons learned are presented for the exploration, preparation, implementation, and sustainment phases. Conclusions: This program has the potential to be flexibly replicated at other universities to assist with graduate student mental health. It provides unique supports for recipients and unique training opportunities for student facilitators.

9.
Quant Plant Biol ; 5: e5, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774130

RESUMO

Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.

10.
Biochim Biophys Acta ; 1823(11): 2046-56, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22542781

RESUMO

Ubiquitin (Ub) is a small protein highly conserved among eukaryotes and involved in practically all aspects of eukaryotic cell biology. Polymeric chains assembled from covalently-linked Ub monomers function as molecular signals in the regulation of a host of cellular processes. Our previous studies have shown that the predominant state of Lys48-linked di- and tetra-Ub chains at near-physiological conditions is a closed conformation, in which the Ub-Ub interface is formed by the hydrophobic surface residues of the adjacent Ub units. Because these very residues are involved in (poly)Ub interactions with the majority of Ub-binding proteins, their sequestration at the Ub-Ub interface renders the closed conformation of polyUb binding incompetent. Thus the existence of open conformation(s) and the interdomain motions opening and closing the Ub-Ub interface is critical for the recognition of Lys48-linked polyUb by its receptors. Knowledge of the conformational properties of a polyUb signal is essential for our understanding of its specific recognition by various Ub-receptors. Despite their functional importance, open states of Lys48-linked chains are poorly characterized. Here we report a crystal structure of the open state of Lys48-linked di-Ub. Moreover, using NMR, we examined interactions of the open state of this chain (at pH4.5) with a Lys48-linkage-selective receptor, the UBA2 domain of a shuttle protein hHR23a. Our results show that di-Ub binds UBA2 in the same mode and with comparable affinity as the closed state. Our data suggest a mechanism for polyUb signal recognition, whereby Ub-binding proteins select specific conformations out of the available ensemble of polyUb chain conformations. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.


Assuntos
Enzimas Reparadoras do DNA/química , Proteínas de Ligação a DNA/química , Lisina/química , Poliubiquitina/química , Enzimas Ativadoras de Ubiquitina/química , Cristalografia por Raios X , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Lisina/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Poliubiquitina/metabolismo , Ligação Proteica , Conformação Proteica , Enzimas Ativadoras de Ubiquitina/metabolismo
11.
Depress Anxiety ; 30(2): 123-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23212730

RESUMO

BACKGROUND: Complicated grief (CG) is a bereavement-specific syndrome characterized by traumatic and separation distress lasting over 6 months. Little is known about the role of dissociation experienced during or immediately after the loss of a loved one (i.e., periloss dissociation [PLD]) in CG. The present study aimed to examine the psychometric properties of the PLD-adapted Peritraumatic Dissociative Experiences Questionnaire and its association with symptom severity, treatment response, and drop-out rate. METHODS: PLD data collected as part of a randomized controlled trial of two loss-focused psychotherapy approaches for CG were examined. Treatment-seeking individuals with primary CG (n = 193) were assessed for PLD at the initial visit, 95 of whom were randomized and completed at least one treatment session. RESULTS: The PLD-adapted Peritraumatic Dissociative Experiences Questionnaire was found to be internally consistent (α = 0.91) with good convergent and divergent validity. After controlling for age, gender, time since loss, and current comorbid psychiatric diagnosis, self-reported PLD was associated with greater CG symptom severity (P < .01). However, contrary to our hypotheses, after controlling for age, baseline symptoms severity, psychiatric comorbidity, and treatment arm, PLD was predictive of better treatment response (P < .05) and lower study discontinuation (P < .01). CONCLUSIONS: PLD may be useful in identifying individuals at risk for CG and those who might respond to psychotherapy. Additional research should investigate the relationship of PLD with treatment outcome for different treatment approaches, and whether PLD prospectively predicts the development of CG.


Assuntos
Depressão/terapia , Transtornos Dissociativos/terapia , Pesar , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Transtornos Dissociativos/psicologia , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários , Resultado do Tratamento
12.
Depress Anxiety ; 30(12): 1211-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23495105

RESUMO

BACKGROUND: Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD. METHODS: Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively. RESULTS: Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (ß = -0.140, P = 0.023) and greater impairment (ß = 0.141, P = 0.035) among individuals with AD. CONCLUSIONS: Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.


Assuntos
Transtornos de Ansiedade/psicologia , Luto , Pesar , Qualidade de Vida/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/psicologia , Transtornos Fóbicos/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia
13.
Hum Psychopharmacol ; 28(5): 447-56, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23776033

RESUMO

OBJECTIVE: We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. METHODS: Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. RESULTS: Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug × conditioned stimulus × trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). CONCLUSIONS: Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted.


Assuntos
Citalopram/administração & dosagem , Condicionamento Psicológico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Adulto , Condicionamento Psicológico/fisiologia , Método Duplo-Cego , Extinção Psicológica/fisiologia , Medo/fisiologia , Medo/psicologia , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Nucleic Acids Res ; 39(6): 2445-57, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21087996

RESUMO

Nucleolar Essential Protein 1 (Nep1) is required for small subunit (SSU) ribosomal RNA (rRNA) maturation and is mutated in Bowen-Conradi Syndrome. Although yeast (Saccharomyces cerevisiae) Nep1 interacts with a consensus sequence found in three regions of SSU rRNA, the molecular details of the interaction are unknown. Nep1 is a SPOUT RNA methyltransferase, and can catalyze methylation at the N1 of pseudouridine. Nep1 is also involved in assembly of Rps19, an SSU ribosomal protein. Mutations in Nep1 that result in decreased methyl donor binding do not result in lethality, suggesting that enzymatic activity may not be required for function, and RNA binding may play a more important role. To study these interactions, the crystal structures of the scNep1 dimer and its complexes with RNA were determined. The results demonstrate that Nep1 recognizes its RNA site via base-specific interactions and stabilizes a stem-loop in the bound RNA. Furthermore, the RNA structure observed contradicts the predicted structures of the Nep1-binding sites within mature rRNA, suggesting that the Nep1 changes rRNA structure upon binding. Finally, a uridine base is bound in the active site of Nep1, positioned for a methyltransfer at the C5 position, supporting its role as an N1-specific pseudouridine methyltransferase.


Assuntos
Metiltransferases/química , Proteínas de Ligação a RNA/química , Proteínas Ribossômicas/química , Proteínas de Saccharomyces cerevisiae/química , Sequência de Aminoácidos , Proteínas Arqueais/química , Archaeoglobus fulgidus/enzimologia , Domínio Catalítico , Dimerização , Metiltransferases/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Pseudouridina/metabolismo , RNA/química , Proteínas Ribossômicas/metabolismo , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/metabolismo
15.
J Vet Intern Med ; 37(1): 37-46, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36482834

RESUMO

BACKGROUND: There has been a recent association between nontraditional diets and development of diet-associated dilated cardiomyopathy (DCM) in dogs. HYPOTHESIS/OBJECTIVES: To compare echocardiographic measurements and cardiac biomarkers between healthy dogs eating nontraditional vs traditional diets. We hypothesized that dogs eating nontraditional diets would have lower measures of systolic myocardial performance compared to dogs eating traditional diets. ANIMALS: Forty-six healthy dogs: 23 eating nontraditional diets and 23 eating traditional diets. METHODS: Prospective, cross-sectional study. Dogs were divided into groups based on diet ingredients. Dogs underwent 2-dimensional (2D), 3-dimensional (3D), and Doppler echocardiographic examinations and analysis of plasma N-terminal prohormone of B-type natriuretic peptide, serum cardiac troponin I, and whole blood and plasma taurine concentrations. RESULTS: Mean 2D ejection fraction (EF) was lower for dogs eating nontraditional diets (48.65 ± 7.42%) vs dogs eating traditional diets (56.65 ± 4.63%; P < .001; mean difference 8.0% [4.0%-12.0%] 95% confidence interval [CI]). Mean 3D EF was lower for dogs eating nontraditional diets (45.38 ± 7.35%) vs dogs eating traditional diets (57.58 ± 4.84%; P < .001; 12.0% [8.0%-16.0%] 95% CI). Mean 2D left ventricular end-systolic volumes, indexed to body weight, were significantly higher in dogs eating nontraditional diets (1.46 ± 0.08 mL/kg) vs dogs eating traditional diets (1.06 ± 0.08 mL/kg; P = .002; 0.4 mL/kg [0.18-0.62 mL/kg] 95% CI). CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy dogs eating nontraditional diets had lower indices of systolic function and larger left ventricular volumes compared to dogs eating traditional diets. Screening of apparently healthy dogs eating nontraditional diets might allow for early detection of diet-associated DCM.


Assuntos
Cardiomiopatia Dilatada , Doenças do Cão , Animais , Cães , Biomarcadores , Cardiomiopatia Dilatada/veterinária , Estudos Transversais , Dieta/veterinária , Doenças do Cão/diagnóstico , Ecocardiografia/veterinária , Ecocardiografia/métodos , Estudos Prospectivos
16.
Anxiety Stress Coping ; 36(3): 366-381, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35603928

RESUMO

BACKGROUND: The co-occurrence of childhood trauma and posttraumatic stress disorder (PTSD) is highly prevalent and clinically significant. Existing research emphasizes the role of emotion regulation in the relation between childhood trauma and PTSD. Yet, research in this area has almost exclusively examined the influence of strategies aimed at regulating negative emotions, such as anger and sadness. OBJECTIVE: To extend existing research, the current study examined underlying roles of strategies for regulating positive emotions (i.e., self- and emotion-focused positive rumination and positive dampening) in the association between childhood trauma severity and PTSD symptoms. PARTICIPANTS AND SETTING: Participants were 320 trauma-exposed community individuals who reported past 30-day substance use (Mage = 35.78, 50.3% men, 81.6% white). METHOD: Analyses examined whether childhood trauma severity was indirectly related to PTSD symptoms through self-focused positive rumination, emotion-focused positive rumination, and positive dampening. RESULTS: Positive dampening, but not positive self- and emotion-focused positive rumination, indirectly explained associations between childhood trauma severity and PTSD symptoms (B = .17, SE = .03, 95% CI [.12, .24]). CONCLUSIONS: These findings highlight the potential utility of targeting positive dampening in the treatment of PTSD symptoms among individuals who use substances with a history of childhood trauma.


Assuntos
Experiências Adversas da Infância , Regulação Emocional , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/psicologia , Emoções , Transtornos Relacionados ao Uso de Substâncias/psicologia
17.
Front Genome Ed ; 4: 957289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120530

RESUMO

Bacterial cells are widely used to produce value-added products due to their versatility, ease of manipulation, and the abundance of genome engineering tools. However, the efficiency of producing these desired biomolecules is often hindered by the cells' own metabolism, genetic instability, and the toxicity of the product. To overcome these challenges, genome reductions have been performed, making strains with the potential of serving as chassis for downstream applications. Here we review the current technologies that enable the design and construction of such reduced-genome bacteria as well as the challenges that limit their assembly and applicability. While genomic reductions have shown improvement of many cellular characteristics, a major challenge still exists in constructing these cells efficiently and rapidly. Computational tools have been created in attempts at minimizing the time needed to design these organisms, but gaps still exist in modelling these reductions in silico. Genomic reductions are a promising avenue for improving the production of value-added products, constructing chassis cells, and for uncovering cellular function but are currently limited by their time-consuming construction methods. With improvements to and the creation of novel genome editing tools and in silico models, these approaches could be combined to expedite this process and create more streamlined and efficient cell factories.

18.
J Am Coll Health ; : 1-10, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881773

RESUMO

OBJECTIVE: Graduate students frequently experience anxiety, depression, and psychological distress. Counseling centers struggle to meet this need. Brief, skills-based treatments to mitigate burgeoning or mild mental health problems could alleviate this problem. PARTICIPANTS: Participants were 51 graduate students in years one through seven of their respective programs. METHODS: We examined a single-session virtual cognitive behavioral workshop and outcomes up to 6-months later. RESULTS: The program was feasible, acceptable, and beneficial for mood, anxiety, and emotion regulation, even during the COVID-19 pandemic. A majority of participants reported ongoing skills use at follow-up. Primary barriers to more frequent use were forgetting, time constraints, and difficulty when experiencing strong emotions. Few participants endorsed expecting that skills would not be helpful or forgetting how to use skills. CONCLUSIONS: This intervention may provide scalable, much needed aid to graduate schools. Moreover, results highlight opportunities for further enhancing brief interventions.

19.
J Am Vet Med Assoc ; 259(S1): 1-3, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35066474

RESUMO

In collaboration with the American College of Veterinary Radiology.


Assuntos
Radiologia , Animais , Humanos , Radiografia , Estados Unidos
20.
BMJ Open ; 12(8): e065005, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36041771

RESUMO

OBJECTIVE: Canadian fetal alcohol spectrum disorder (FASD) guidelines encourage an age-specific interdisciplinary diagnostic approach. However, there is currently no standard-of-care regarding FASD diagnosis disclosure and few studies document Canadian FASD clinical capacity. Our objectives were to describe clinical capacity (defined as skills and resources) for FASD assessment, diagnosis, disclosure and support in Canada. DESIGN, SETTING AND PARTICIPANTS: Data were drawn from the CanDiD study, a cross-sectional investigation of Canadian FASD clinical capacity. Forty-one clinics participated in the study. Data were collected in 2021 on the number and types of health professionals included in the assessment and diagnostic teams, the presence (or absence) of a minor patient when the FASD diagnosis is disclosed to parents/guardians, who is responsible for the diagnosis disclosure, the use of explanatory tools, and the types of support/counselling services available. The proportion of clinics that follow the Canadian interdisciplinary diagnostic guidelines by age group is described among participating clinics. RESULTS: Overall, 21, 13 and 7 specialised FASD clinics were in Western/Northern, Central and Atlantic Canada, respectively. The number of referrals per year surpassed the number of diagnostic assessments completed in all regions. Approximately, 60% of clinics who diagnosed FASD in infants and preschool children (n=4/7 and 15/25, respectively) followed the interdisciplinary guidelines compared with 80% (n=32/40) in clinics who diagnosed school-aged children/adolescents. Diagnostic reporting practices were heterogeneous, but most used an explanatory tool with children/adolescents (67%), offered support/counselling (90-95%) and used case-by-case approach (80%) when deciding who would disclose the diagnosis to the child/adolescent and when. CONCLUSIONS: Limited diagnostic capacity and lack of FASD resources across Canada highlights a critical need for continued FASD support. This study identifies gaps in assessment, diagnosis and reporting practices for FASD in children/adolescents across Canada.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Adolescente , Canadá , Criança , Pré-Escolar , Estudos Transversais , Revelação , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Humanos , Lactente , Gravidez , Encaminhamento e Consulta
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