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1.
PLoS One ; 19(7): e0305004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959439

RESUMO

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Humanos , Feminino , Gravidez , Hidrocarbonetos Policíclicos Aromáticos/urina , Estados Unidos , Adulto , Estudos de Coortes , Exposição Materna/efeitos adversos , Adulto Jovem
2.
Clin Pharmacol Drug Dev ; 13(4): 410-418, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311833

RESUMO

Baxdrostat is a selective small-molecule aldosterone synthase inhibitor in development for treatment of hypertension and chronic kidney disease. This phase 1, open-label, parallel-group study assessed the safety and pharmacokinetics (PK) of baxdrostat in participants with varying degrees of renal function. Participants were enrolled into control (estimated glomerular filtration rate [eGFR] ≥60 mL/min), moderate to severe renal impairment (eGFR 15-59 mL/min), or kidney failure (eGFR <15 mL/min) groups and received a single 10-mg baxdrostat dose followed by 7 days of inpatient PK blood and urine sampling. Safety was assessed by adverse events, clinical laboratory evaluations, vital signs, physical examinations, and electrocardiograms (ECGs). Thirty-2 participants completed the study. There were no deaths and only 1 mild drug-related adverse event (diarrhea). No clinically meaningful changes in laboratory values, vital signs, physical examinations, or ECGs occurred. Plasma concentration-time curves of baxdrostat were similar among all groups. Urine PK parameters were similar (approximately 12% excreted) in the moderate to severe renal impairment and control groups. Inadequate urine production in the kidney failure group resulted in minimal urinary baxdrostat excretion. Renal impairment had no significant impact on systemic exposure or clearance of baxdrostat, suggesting that dose adjustment due to PK differences in patients with kidney disease is unnecessary.


Assuntos
Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Citocromo P-450 CYP11B2 , Taxa de Filtração Glomerular , Rim
3.
Int J Spine Surg ; 17(S3): S35-S43, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38050045

RESUMO

The technology surrounding spinal fusion surgery has continuously evolved in tandem with advancements made in bioengineering. Over the past several decades, developments in biomechanics, surgical techniques, and materials science have expanded innovation in the spinal implant industry. This narrative review explores the current state of implant surface technologies utilized in spinal fusion surgery. This review covers various types of implant surface materials, focusing on interbody spacers composed of modified titanium, polyetheretherketone, hydroxyapatite, and other materials, as well as pedicle screw surface modifications. Advantages and disadvantages of the different surface materials are discussed, including their biocompatibility, mechanical properties, and radiographic visibility. In addition, this review examines the role of surface modifications in enhancing osseointegration and reducing implant-related complications and, hopefully, improving patient outcomes. The findings suggest that while each material has its potential advantages, further research is needed to determine the optimal surface properties for enhancing spinal fusion outcomes.

4.
Clin Spine Surg ; 36(9): 391-397, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37798824

RESUMO

STUDY DESIGN: Narrative review. OBJECTIVES: The purpose of this study was to provide a review of the current evidence on the impact of posterior cervical foraminotomy (PCF) performed before or after cervical disk replacement (CDR). SUMMARY OF BACKGROUND DATA: The impact of PCF on outcomes in the setting of CDR is an evolving field, given the recent widespread adoption of CDR and the relative rarity of patients who have undergone both procedures. METHODS: A literature search was conducted using PubMed to determine current evidence regarding the indications, outcomes, and biomechanical effects of CDR and PCF when performed alone or in combination. RESULTS: When radicular symptoms persist following PCF, a CDR can be safely performed to provide further decompression. Conversely, a PCF can be safely performed following CDR for these same indications. The biomechanical effects of these procedures in combination demonstrate maintained stability when the facetectomy is less than 50% of the facet joint. Studies demonstrate that stability is not significantly decreased by the presence, amount, or level of posterior foraminotomies in the setting of CDR. CONCLUSIONS: A PCF can be safely performed before or after cervical disk arthroplasty for recurrent radicular symptoms. LEVEL OF EVIDENCE: Level V.


Assuntos
Foraminotomia , Radiculopatia , Humanos , Foraminotomia/métodos , Resultado do Tratamento , Radiculopatia/cirurgia , Vértebras Cervicais/cirurgia , Pescoço
5.
Child Neuropsychol ; 29(2): 235-254, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35678295

RESUMO

Although predictive associations between childhood executive control (EC) and adolescent substance use have been established in prior research, the developmental pathways involved in these long-term links have not been well understood. The goal of the current study was to investigate the degree to which aggressive behaviors, including both physical and relational aggression, and prosocial behaviors in elementary school operate as developmental pathways between preschool EC and adolescent substance use, while accounting for participants' age, sex, family history of substance use, and family socioeconomic status. Participants were 329 youth (49% male; 63.6% European American) who were recruited to participate in a study between 2006 and 2012 while youth were in preschool and elementary school and followed into adolescence. The sample was recruited from a small Midwestern city in the United States. EC was assessed with performance-based tasks when children were 5 years 3 months. Youth behaviors with peers were reported by teachers when participants were in elementary school. Self-reports of the substance use initiation (e-cigarettes, cigarettes, alcohol, and marijuana) were obtained in adolescence via phone surveys. Mediation analyses revealed a statistically significant indirect effect from preschool EC to adolescent substance use through youth's engagement in relational aggression in elementary school (b = > -0.22 [-0.51; -0.08]; ß = > -0.18). Our results suggest that developmental pathways to adolescent substance use may begin in preschool, setting the stage for susceptibility to engagement in relational aggression, which increases, in turn, youth's likelihood for substance use initiation in adolescence.


Assuntos
Comportamento do Adolescente , Sistemas Eletrônicos de Liberação de Nicotina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Criança , Masculino , Pré-Escolar , Adolescente , Feminino , Função Executiva , Altruísmo , Agressão , Grupo Associado , Estudos Longitudinais
6.
Leukemia ; 37(3): 560-570, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36550214

RESUMO

Fms-like tyrosine kinase 3 (Flt3) tyrosine kinase inhibitors (Flt3-TKI) have improved outcomes for patients with Flt3-mutated acute myeloid leukemia (AML) but are limited by resistance and relapse, indicating persistence of leukemia stem cells (LSC). Here utilizing a Flt3-internal tandem duplication (Flt3-ITD) and Tet2-deleted AML genetic mouse model we determined that FLT3-ITD AML LSC were enriched within the primitive ST-HSC population. FLT3-ITD LSC showed increased expression of the CXCL12 receptor CXCR4. CXCL12-abundant reticular (CAR) cells were increased in Flt3-ITD AML marrow. CXCL12 deletion from the microenvironment enhanced targeting of AML cells by Flt3-TKI plus chemotherapy treatment, including enhanced LSC targeting. Both treatment and CXCL12 deletion partially reduced p38 mitogen-activated protein kinase (p38) signaling in AML cells and further reduction was seen after treatment in CXCL12 deleted mice. p38 inhibition reduced CXCL12-dependent and -independent maintenance of both murine and human Flt3-ITD AML LSC by MSC and enhanced their sensitivity to treatment. p38 inhibition in combination with chemotherapy plus TKI treatment leads to greater depletion of Flt3-ITD AML LSC compared with CXCL12 deletion. Our studies support roles for CXCL12 and p38 signaling in microenvironmental protection of AML LSC and provide a rationale for inhibiting p38 signaling to enhance Flt3-ITD AML targeting.


Assuntos
Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms , Animais , Humanos , Camundongos , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Sistema de Sinalização das MAP Quinases , Mutação , Transdução de Sinais , Células-Tronco/metabolismo , Microambiente Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno
7.
ESMO Open ; 7(5): 100562, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35987165

RESUMO

BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/metabolismo , Fatores de Transcrição Forkhead , Microambiente Tumoral
8.
Environ Int ; 164: 107246, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35453081

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous chemicals with mechanisms of toxicity that include endocrine disruption. We examined associations of prenatal urinary PAH with spontaneous preterm birth (PTB) and gestational age (GA) at birth. We also assessed whether infant sex modifies the association of PAH exposure with spontaneous PTB and GA at birth. METHODS: Participants included 1,677 non-smoking women from three cohorts (CANDLE, TIDES, and GAPPS) in the ECHO PATHWAYS Consortium. Twelve monohydroxylated-PAHs were measured in second trimester maternal urine. Seven metabolites with >60% overall detection were included in analyses: 1-hydroxynaphthalene [1-OH-NAP], 2-hydroxynaphthalene [2-OH-NAP], 2-hydroxyphenanthrene [2-OH-PHEN], 3-hydroxyphenanthrene [3-OH-PHEN], 1/9-hydroxyphenanthrene [1/9-OH-PHEN], 2/3/9-hydroxyfluorene [2/3/9-OH-FLUO], and 1-hydroxypyrene [1-OH-PYR]. Logistic and linear regression models were fit for spontaneous PTB and GA among births ≥34 weeks, respectively, with log10-transformed OH-PAH concentrations as the exposure, adjusted for specific gravity and suspected confounders. Effect modification by infant sex was assessed using interaction terms and marginal estimates. RESULTS: Percent detection was highest for 2-OH-NAP (99.8%) and lowest for 1-OH-PYR (65.2%). Prevalence of spontaneous PTB was 5.5% (N = 92). Ten-fold higher 2-OH-NAP exposure was associated with 1.60-day (95% CI: -2.92, -0.28) earlier GA at birth. Remaining associations in the pooled population were null. Among females, we observed significant inverse associations between 1-OH-PYR and PTB (OR: 2.65 [95% CI: 1.39, 5.05]); and 2-OH-NAP with GA: -2.46 days [95% CI: -4.15, -0.77]). Among males, we observed an inverse association between 2/3/9-OH-FLUO and PTB (OR = 0.40 [95% CI: 0.17,0.98]). ORs for PTB were higher among females than males for 2-OH-PHEN (p = 0.02) and 1-OH-PYR (p = 0.02). DISCUSSION: We observed inverse associations of 2-OH-NAP exposure with GA and null associations of remaining OH-PAHs with GA and PTB. Females may be more susceptible to spontaneous PTB or shorter GA following prenatal exposure to some OH-PAHs. This study is the first to assess sex-specific OH-PAH toxicity in relation to spontaneous PTB and GA.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores/urina , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/urina , Gravidez , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
9.
Addict Behav ; 119: 106923, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33826966

RESUMO

BACKGROUND: Adolescent cigarette smoking has continued to decline, whereas electronic cigarette (e-cigarette) use has increased dramatically among youth. Nicotine use in any form, even at low levels, during adolescence can have adverse consequences, particularly for low-income individuals. To elucidate potential early intervention targets, this study examined childhood executive control (EC), a set of cognitive processes for directing attention and behavior, in relation to adolescent cigarette and e-cigarette onset, testing for differential prediction by poverty level. METHOD: Participants were 313 children (51% female, 64% European American) recruited in a small city in the Midwestern United States beginning in 2006 and then followed into adolescence between ages 14 and 16 years. EC was measured in the laboratory with performance-based tasks when children were age 5 years, 3 months. Self-reports of cigarette onset and e-cigarette onset were obtained in adolescence (Mage = 15.65 years). Overall, 24% of the sample was at or below the poverty line. RESULTS: Cigarette onset was higher in the poverty group (17%) than in the non-poverty (8%) group, but e-cigarette onset did not differ by poverty level (36% poverty versus 38% non-poverty). Multiple group structural equation modeling revealed a statistically significant group difference such that EC ability was a significant negative predictor of e-cigarette onset for poverty but not for non-poverty youth. A similar group difference was evident as a trend for cigarette onset. CONCLUSIONS: Because EC has been shown to be modifiable, early interventions to improve EC for children living in poverty might help prevent adolescent e-cigarette onset.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adolescente , Criança , Pré-Escolar , Função Executiva , Feminino , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Pobreza
10.
J Am Vet Med Assoc ; 258(7): 740-747, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33754813

RESUMO

CASE DESCRIPTION: An 8-month-old 41.2-kg (90.6-lb) sexually intact male Dogue de Bordeaux with urinary incontinence and signs of nausea was referred for further evaluation and treatment of bilateral hydronephrosis, hydroureter, and ectopic ureters. CLINICAL FINDINGS: Clinicopathologic analyses revealed urine specific gravity and serum concentrations of urea nitrogen and creatinine within reference limits. Abdominal ultrasonography and CT revealed unilateral abdominal cryptorchidism, ureters that bilaterally passed dorsal to and appeared compressed by the external iliac arteries (retroiliac ureters), and bilateral hydronephrosis, hydroureter, and ectopic ureters. On CT, minimal uptake of contrast medium by the right kidney indicated either a lack of renal function or ureteral obstruction. TREATMENT AND OUTCOME: The dog underwent exploratory laparotomy, right ureteronephrectomy, left neoureterocystostomy, bilateral castration, and incisional gastropexy without complication and was discharged 2 days postoperatively. Eleven days after surgery, the dog had improved but continued urinary incontinence, improved left hydronephrosis and hydroureter, and serum concentrations of urea nitrogen and creatinine within reference limits. At 24 months after surgery, the dog was reportedly clinically normal, other than having persistent urinary incontinence. CLINICAL RELEVANCE: To our knowledge, this was the first report of a dog with retroiliac ureters and compression-induced ureteral obstruction with secondary hydroureter and hydronephrosis. Retroiliac ureters should be considered as a differential diagnosis in young dogs with ureteral obstruction. Our findings indicated that a good outcome was possible for a dog with retroiliac ureters treated surgically; however, the presence of additional congenital anomalies should be considered and may alter the prognosis in dogs with retroiliac ureters.


Assuntos
Doenças do Cão , Hidronefrose , Ureter , Obstrução Ureteral , Incontinência Urinária , Animais , Doenças do Cão/cirurgia , Cães , Hidronefrose/etiologia , Hidronefrose/cirurgia , Hidronefrose/veterinária , Masculino , Ureter/cirurgia , Obstrução Ureteral/veterinária , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgia , Incontinência Urinária/veterinária
11.
Vet Radiol Ultrasound ; 62(4): 445-454, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33634942

RESUMO

Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.


Assuntos
Neoplasias Encefálicas/veterinária , Doenças do Cão/diagnóstico por imagem , Imageamento por Ressonância Magnética/veterinária , Meningoencefalite/veterinária , Animais , Neoplasias Encefálicas/patologia , Doenças do Cão/patologia , Cães , Granuloma/complicações , Masculino , Meningoencefalite/complicações , Meningoencefalite/diagnóstico por imagem , Estudos Retrospectivos
12.
Vet Radiol Ultrasound ; 62(3): 271-281, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33439529

RESUMO

Radiographic assessment of heart size is important for clinical management of dogs with cardiovascular disease (CVDz). We sought to compare the ability of vertebral heart size (VHS), vertebral left atrial size (VLAS), and radiologists' assessment of left atrial size (RadLAE) to predict echocardiographic left atrial size (EchoLAE), an important marker of left heart disease severity. We also compared the ability of VHS and VLAS to predict echocardiographic criteria for ACVIM stage B2 (EchoB2) in dogs with myxomatous mitral valve disease (MMVD). This prospective observational study enrolled 183 dogs with known or suspected CVDz that had an echocardiographic examination and thoracic radiographs obtained within 24 h. Compared to increased VHS, VLAS >2.3 was a more accurate predictor of EchoLAE (P = .002). VLAS >2.3 and RadLAE (both P <.0001) were independently associated with EchoLAE but VHS was not (P = .45). Optimal cutoffs for VLAS and VHS to predict EchoLAE were >2.3 vertebrae (sensitivity [Sn] = 90.3%, specificity [Sp] = 73.6%) and >11.1 vertebrae (Sn = 75.8%, Sp = 76.0%), respectively. Diagnostic accuracy of VLAS (AUC 0.84, 95% CI 0.73-0.92) and VHS (AUC 0.78, 95% CI 0.66-0.88) to predict EchoB2 in dogs with subclinical MMVD (n = 64) were not significantly different (P = .17). Results demonstrate that VLAS and RadLAE were superior indicators of EchoLAE compared to VHS in dogs with known or suspected CVDz. Both VLAS and VHS are useful predictors of EchoB2 in dogs with subclinical MMVD. When echocardiography is unavailable, VLAS represents a useful radiographic measurement to aid clinical management of dogs with known or suspected CVDz.


Assuntos
Cardiomegalia/veterinária , Doenças do Cão/diagnóstico por imagem , Animais , Cardiomegalia/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Doenças das Valvas Cardíacas/veterinária , Masculino , Estudos Prospectivos
13.
bioRxiv ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33442684

RESUMO

The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

14.
Prev Sci ; 21(5): 681-690, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32372380

RESUMO

This study examined whether cognitive processes in preschool, conceptualized as a unitary construct of executive control (EC) as well as foundational cognitive abilities (FCA), predict both maladaptive and adaptive functioning in middle childhood and mediate associations between early childhood socio-familial stress and those functional outcomes. Performance-based, multidimensional, and age-appropriate measures of EC and FCA were collected in a laboratory setting from 313 preschool-age children at age 5, along with questionnaire data from children and their parents on three dimensions of early socio-familial stress and parent smoking. Parent, teacher, and child self-report data on 285 of these children were obtained when they were in grade 3 or 4. Middle childhood data were used to create indices of maladaptive and adaptive functioning. A bi-factor structural equation modeling analysis captured distinct dimensions of preschool EC and FCA and was used to test the hypothesized pathways. EC had a statistically significant negative association with later maladaptive functioning. FCA, but not EC, served as a mediator in links between each type of family stressor and both maladaptive and adaptive functioning in middle childhood. Results suggest that EC may play a role in predicting maladaptation, whereas early childhood FCA may operate as an intervening variable in pathways from early family stressors to subsequent maladaptation as well as adaptation. Findings point to the need to address FCA by reducing early family stressors. Early interventions that enhance cognitive abilities may help reduce maladaptive and promote adaptive functioning later in childhood, thereby potentially preventing, in turn, later behavioral problems.


Assuntos
Adaptação Psicológica , Cognição , Função Executiva , Comportamento Problema , Estresse Psicológico/psicologia , Criança , Pré-Escolar , Análise Fatorial , Feminino , Humanos , Masculino , Observação , Inquéritos e Questionários
15.
Addiction ; 115(1): 19-31, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31140213

RESUMO

BACKGROUND AND AIMS: Alcohol use and marijuana use tend to be social activities among adolescents. Some youth use alcohol or marijuana while alone. This article provides a framework for examining the risk factors for and consequences of solitary alcohol and marijuana use, grounded in a motivational model that emphasizes coping with negative emotions, and provides the first systematic review of research on solitary alcohol and marijuana use among middle school- and high school-aged adolescents in the United States. METHODS: PubMed, PsycINFO and Web of Science were searched. Articles were included if they mention solitary alcohol or marijuana (or illicit drug) use among adolescents aged 12-18 years. Studies on non-human animals, college students, non-English language publications and articles exclusively about solitary tobacco or inhalant use were excluded. Overall, 22 articles were selected. RESULTS: Prevalence of adolescent solitary alcohol and marijuana use was relatively high (e.g. 14% life-time solitary drinking in the general adolescent population), particularly in high-risk subgroups (e.g. 38.8% life-time solitary drinking in a sample of youth recruited from clinical and community settings). Risk factors for solitary alcohol and marijuana use include earlier onset and heavier use, coping motives, negative emotions and positive expectancies about use. Solitary alcohol and marijuana use are prospectively associated with later substance use disorder (SUD) symptoms, diminished academic performance and perceived health. CONCLUSIONS: Approximately 1 in 7 adolescents in the US appear to have engaged in solitary alcohol and marijuana use at some point. It is positively associated with extent of drinking and marijuana use, cop;ing motives, negative emotions, and positive expectancies, as well as subsequent SUD symptoms and poor academic and health-related outcomes.


Assuntos
Comportamento do Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Uso da Maconha/epidemiologia , Espaço Pessoal , Isolamento Social , Adolescente , Criança , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Estados Unidos/epidemiologia
16.
Curr Oncol ; 26(4): e458-e465, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31548813

RESUMO

Objective: Paraneoplastic neurologic syndrome (pns) is a rare condition indirectly caused by an underlying malignancy. In many cases, the malignancy is occult at the time of the pns diagnosis, and the optimal diagnostic modality to detect the underlying tumour is unclear. In the present study, we aimed to assess the utility of 18F-fluorodeoxyglucose positron-emission tomography (fdg-pet) or pet integrated with computed tomography (pet/ct) in the investigation of these patients. Methods: We retrospectively analyzed data from the PET Access Program (pap) database in the province of Ontario to identify patients who underwent fdg-pet/ct imaging as part of a workup for pns. In all patients, prior conventional imaging was negative or indeterminate. To determine the diagnostic accuracy of fdg-pet/ct, data about demographics, presenting symptoms, and biochemical and radiologic workup, including fdg-pet/ct imaging results, were compared with data collected by the Ontario Cancer Registry (ocr). A systematic review of the literature and meta-analysis using our study inclusion criteria were performed for studies of fdg-pet accuracy. Results: Of 29 patients identified in the pap database, 9 had fdg-pet/ct results suspicious for malignancy. When correlated with data from the ocr, 5 fdg-pet/ct results were informative, resulting in a detection rate of 17%. Local sensitivity and specificity were 0.83 and 0.83 respectively. Two studies meeting our criteria were identified in the literature. The pooled sensitivity and specificity from the literature and local data were 0.88 and 0.90 respectively. Conclusions: When investigating for underlying malignancy in patients with suspected pns and negative conventional imaging, pet has high sensitivity and specificity.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
17.
J Trauma Stress ; 32(5): 753-763, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31441982

RESUMO

Trauma screening is an important element for providing trauma-informed services to youth in residential care. Unfortunately, lack of time and resources may deter clinicians from conducting trauma screening at intake. This study tested the psychometric properties of the Brief Trauma Symptom Screen for Youth (BTSSY), which could be used during intake into residential care. Participants included 572 youth, ages 10-18 years (M = 14.28 years, SD = 2.31), of whom 58.9% were boys, 78.7% were Caucasian, 51.7% were youth receiving services in residential care, 15.6% were youth with clinical needs, and 32.7% were typically developing youth from the local community. Participants completed the BTSSY; other questionnaires of psychopathology, childhood maltreatment, and symptomology of posttraumatic stress disorder (PTSD); and diagnostic interviews, which were conducted by licensed psychiatrists. The total BTSSY score had a good composite reliability (CR) of .80 and was valid based on a significant positive correlation, r = .64, with the UCLA PTSD-Reaction Index. The BTSSY score was also fair, area under the curve = .75, at detecting a diagnosis of PTSD from a psychiatrist. Significant group differences in the BTSSY scores were found between youth with a diagnosis of PTSD and the other two groups, with moderate-to-large effect sizes, ds = 0.73-1.22. Preliminary results indicated the BTSSY may be a useful screening tool for identifying youth at residential care intake who may need additional assessment for PTSD. Limitations and implications for future research and practice are discussed.


Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Psicometría de la escala breve de síntomas de trauma para jóvenes en atención residencial TAMIZAJE BREVE DE SÍNTOMAS DE TRAUMA PARA JOVENES La detección de los traumas es un elemento importante para proporcionar servicios informados en el trauma a los jóvenes en atención residencial. Desafortunadamente, la falta de tiempo y recursos puede impedir a los médicos realizar detección de traumas en el ingreso. Este estudio probó las propiedades psicométricas de la Escala Breve de Síntomas de Trauma para Jóvenes (BTSSY en su sigla en inglés), que podría usarse durante el ingreso a la atención residencial. Los participantes incluyeron 572 jóvenes, de 10 a 18 años (M = 14.28 años, DE = 2.31), de los cuales 58.9% eran niños, 78.7% eran caucásicos, 51.7% eran jóvenes que recibían servicios de atención residencial, 15.6% eran jóvenes con necesidades clínicas, y 32.7% eran jóvenes con desarrollo normativo de la comunidad local. Los participantes completaron el BTSSY; otros cuestionarios de psicopatología, maltrato infantil, y sintomatología del trastorno de estrés postraumático (TEPT); y entrevistas de diagnóstico, realizadas por psiquiatras calificados. El puntaje BTSSY total tuvo una buena confiabilidad compuesta (CR en su sigla en inglés) de .80 y fue válido en base a una correlación positiva significativa, r = .64, con el Índice de Reacción del TEPT de UCLA. El puntaje BTSSY también fue favorable, área bajo la curva = .75, al detectar un diagnóstico del TEPT de un psiquiatra. Se encontraron diferencias significativas entre los grupos en los puntajes BTSSY entre los jóvenes con diagnóstico del TEPT y los otros dos grupos, con tamaños del efecto moderados a grandes, ds = 0.73-1.22. Los resultados preliminares indicaron que el BTSSY puede ser una herramienta útil de detección para identificar a los jóvenes que reciben atención residencial y que pueden necesitar una evaluación adicional para el TEPT. Se discuten las limitaciones e implicaciones para futuras investigaciones y la práctica.


Assuntos
Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários , Avaliação de Sintomas/métodos , Adolescente , Criança , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Psicometria , Reprodutibilidade dos Testes , Instituições Residenciais , Fatores Sexuais
19.
Photoacoustics ; 11: 14-27, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30073147

RESUMO

Optoacoustic imaging is a medical imaging modality that uses optical excitation and acoustic detection to generate images of tissue structures based up optical absorption within a tissue sample. This imaging modality has been widely explored as a tool for a number of clinical applications, including cancer diagnosis and wound healing tracking. Recently, the optoacoustic imaging community has published a number of reports of hand-held optoacoustic imaging devices and platforms; these hand-held configurations improve the modality's potential for commercial clinical implementation. Here, we review recent advancements in hand-held optoacoustic imaging platforms and methods, including recent pre-clinical applications, and we present an overview of the remaining limitations in optoacoustic imaging that must be addressed to increase the translation of the modality into commercial and clinical use.

20.
J Child Fam Stud ; 27(3): 717-724, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29861618

RESUMO

This study examined whether there are subgroups of families with distinct profiles of prenatal/birth contextual risk, and whether subgroup membership was differentially related to adolescent substance use. Data from the Northern Finland Birth Cohort 1986 were used. A five-class model provided the most meaningful solution. Large Family Size (7.72%) and Low Risk (69.69%) groups had the lowest levels of alcohol, cigarette, and illegal drug use. Similar high levels for each of the three substance-related outcomes were found for Parent Substance Misuse (11.20%), Maternal School Dropout (4.66%), and Socioeconomic Disadvantage (6.72%) groups. Maternal smoking and drinking while pregnant and paternal heavy alcohol use were found to be key prenatal risk factors that tended to cluster together and co-occur with other prenatal risk factors differently for different subgroups of youth.

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