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1.
Infant Ment Health J ; 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843073

RESUMO

A pilot randomized controlled trial (RCT) was conducted in El Salvador of an intervention ('Thula Sana') previously shown to enhance maternal sensitivity and infant security of attachment in a South African sample. In El Salvador, trained community workers delivered the intervention from late pregnancy to 6 months postpartum as part of a home-visiting programme. The sample comprised 64 pregnant adolescent women, aged 14-19 years, living in predominantly rural settings. They were randomised to receive either the intervention or normal care. Demographic information was collected at baseline and, immediately post-intervention, blind assessments were made of parental sensitivity and infant emotion regulation. The intervention was found to have a substantial positive impact on maternal sensitivity. Further, compared to control group, infants in the intervention group showed more regulated behaviour: in a social challenge task they showed more attempts to restore communication, and in a non-social challenge task they showed more social and goal-directed behaviour. This replication and extension of the South African findings in a small El Salvador sample shows promise and justifies the conduct of a large-scale RCT in a Central or South American context.

2.
Am J Hematol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075179

RESUMO

Low arginine bioavailability is associated with vaso-occlusive painful crisis (VOC) severity in sickle cell anemia (SCA) and predicts need for pediatric hospitalization. Intravenous arginine therapy has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOC in a phase-two randomized placebo-controlled trial (RCT). Efficacy of oral arginine is unknown. Our objective was to determine the safety and efficacy of oral arginine therapy in Nigerian children with SCA. A double-blind RCT of oral L-arginine-hydrochloride (100 mg/kg TID) was conducted in children with SCA-VOC, aged 5-17 years, hospitalized at two Nigerian sites. The primary outcome measure was analgesic usage, quantified by difference in the mean Analgesic Medication Quantification Scale (MQS). Secondary outcomes included daily pain scores, time-to-crisis-resolution and length-of-hospital-stay. An intention-to-treat analysis was performed. Sixty-eight children (age 5-17 years, mean 10.6 ± 0.4 years; 56% male), were randomized to receive L-arginine (35 patients) or placebo (33 patients). The mean total MQS for the arginine group was 73.4 (95% CI, 62.4-84.3) vs 120.0 (96.7-143.3) for placebo (P < .001). The mean rate of decline in worst pain scores was faster in the arginine arm vs placebo (1.50 [1.23-1.77] vs 1.09 [0.94-1.24] point/d, P = .009). Children receiving arginine had a shorter time-to-crisis-resolution (P = .02), shorter hospital-stay (P = .002) and experienced no serious adverse event. Pain control was more rapid, total analgesic requirement was significantly reduced, and most notably, time-to-crisis-resolution and length-of-hospital-stay were shorter in children with SCA-VOC receiving arginine vs placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA-VOC management.

3.
Infant Ment Health J ; 41(6): 850-858, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32667053

RESUMO

BACKGROUND: Maternal-infant feeding interactions are a primary context for engagement between mothers and their infants, and constitute a unique space in which reciprocity, attunement and maternal sensitivity can be expressed. Increasingly, research demonstrates the importance of the psychological and social nature of the feeding context, and how it may be affected by maternal mental state, feeding skills and sensitivity. As such, feeding interactions may provide useful contexts for observations of maternal sensitivity, reflecting well on day-to-day maternal sensitivity. AIMS AND OBJECTIVES: This paper is a post hoc examination of the impact of an intervention on maternal sensitivity during a feeding interaction when the infants were 6 months old. PARTICIPANTS: A total of 449 women consented to participate in the original intervention and were randomly assigned to the intervention or control groups. Mothers and infants were assessed during pregnancy, and then at 2, 6, 12 and 18 months of infant age. At the 6 month follow-up visit, 79% (354 out of 449) of the participants were retained. Post hoc analyses were conducted on the original sample to determine breastfeeding status. Sixty-nine percent of the women completed the feeding observation at the 6 months follow-up visit, of which 47% reported exclusively breastfeeding and 22% reported bottle-feeding. RESULTS: Results demonstrated that during a feeding interaction, maternal sensitivity was significantly improved among non-breastfeeding mothers who received the intervention. Particularly, maternal responsiveness to infant cues and synchronous interactions was higher among non-breastfeeding intervention mothers compared to control group mothers. The results also show that non-breastfeeding mothers who received the intervention were significantly less intrusive in their interactions with their infants. CONCLUSION: The intervention had particular beneficial effects for mothers who were not breastfeeding and suggest that the intervention offered a protective effect for non-breastfeeding mothers.

4.
Cardiol Young ; 30(2): 162-170, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31973786

RESUMO

BACKGROUND: Sickle cell anaemia is characterised by frequent, sometimes serious events referred to as "crisis". Cardiopulmonary consequences such as pulmonary hypertension and myocardial ischaemia may accompany a serious crisis. OBJECTIVE: To determine the cardiovascular changes that occur during a severe sickle cell crisis. METHODS: A cross-sectional comparative study of sickle cell anaemia in children (5-17 years) admitted during a severe crisis (cases) and those in steady state (controls) was conducted over a 2-year period. Effects of the crisis on the cardiopulmonary system were assessed. The diagnosis of myocardial ischaemia was made using electrocardiography and serological cardiac biomarkers, while cardiac dysfunction and the presence of pulmonary hypertension were determined using echocardiography. The presence of systemic hypertension and tachycardia was also evaluated. RESULTS: A total of 176 patients were recruited, 92 in steady state (male:female ratio, 1.2:1) and 84 in severe crisis (male:female ratio, 1.3:1). The mean age was 10.4 ± 3.2 years for steady state and 10.5 ± 3.4 years for those in crisis. The mean heart rate in crisis was higher than in steady state (p < 0.0001). The blood pressures (systolic, p < 0.0001, diastolic, p < 0.0001, mean, p < 0.0001) as well as myocardial ischaemia scores (p < 0.0001) were higher in patients with crisis than in those in steady state. Similarly, conduction abnormalities, pulmonary hypertension, and ventricular dysfunction were more prevalent in the crisis than in the steady state. CONCLUSION: The present data suggest that sickle cell crisis results in a derangement of clinical, electrocardiographical, and echocardiographical parameters in children with sickle cell anaemia. Further research on these cardiovascular events may improve the overall care of these patients.

5.
J Thromb Haemost ; 18(2): 271-277, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31999059

RESUMO

Inherited protein C (PC) deficiency increases risk of venous thromboembolism (VTE) by 5 to 10-fold in thrombosis-prone families; however, heterozygous PC deficiency alone does not determine that a subject has thrombophilia. Protein C deficient subjects, who lack additional inherited risk factors such as factor V Leiden or have no major acquired risk factors, may not suffer from VTE. In addition, PC deficiency may be acquired, often due to vitamin K antagonist treatment or liver disease. In contrast, homozygous or compound heterozygous PC deficiencies are rare and serious disorders, and affected infants are often in families with no history of PC deficiency or thrombosis. Laboratories commonly use the chromogenic PC assay to diagnose deficiency. Chromogenic assay is recommended due to its good specificity, but this assay fails to detect the rare type 2b deficiency where the defect is due to poor interaction with calcium ions, phospholipid, protein S, and factor Va and factor VIIIa. The clotting-based assay of PC is capable of detecting type 2b deficiency but it has reduced specificity. Importantly, PC level varies with age, adult reference ranges cannot be applied to babies or children and levels may not reach those of adults even in adolescence. Pre-analytical variables in the specimen affect measurement of PC, and can be assay-dependent; for example, a partially clotted sample will have falsely raised PC level by chromogenic assay but reduced level by clotting-based assay. Direct oral anticoagulants falsely raise PC level in the clotting-based assay but the standard chromogenic assay is unaffected.

6.
Eur Respir J ; 55(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31949117

RESUMO

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.

7.
J Child Psychol Psychiatry ; 61(7): 779-788, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31916250

RESUMO

BACKGROUND: Social anxiety disorder (SAD) aggregates in families. To elucidate intergenerational transmission of risk, we examined whether childhood SAD and symptoms of anxiety were prospectively predicted by stable infant temperamental inhibition, maternal SAD, maternal generalized anxiety disorder (GAD) and maternal parenting behaviours. METHODS: We conducted a longitudinal study beginning prenatally with follow-up at 4, 10, 14 and 58 months postnatally. Mothers were assessed for anxiety disorders prenatally and assigned to one of three groups: SAD (n = 67), GAD (n = 56) and nonanxious controls (n = 94). We assessed infant temperamental inhibition at 4 and 14 months, maternal parenting behaviours at 10 and 58 months, and child anxiety disorders and symptoms at 58 months. RESULTS: Child SAD at 58 months was predicted by prenatal maternal SAD (OR = 23.76, 95% CI = 1.15-60.37), but not by prenatal maternal GAD (OR = 7.44, 95% CI = 0.32-124.49), stable temperamental inhibition or maternal behaviours. Child anxiety symptoms at 58 months were predicted specifically by maternal SAD (but not GAD), and also by concurrent maternal intrusiveness. Stable temperamental inhibition moderated the association between 10-month maternal encouragement and 58-month child anxiety symptoms. CONCLUSIONS: We found evidence for specificity of risk for child SAD and anxiety symptoms from maternal SAD compared to maternal GAD. Childhood anxiety symptoms were also predicted by an interaction between a lack of maternal encouragement in infancy and stable temperamental inhibition, as well as concurrent maternal intrusiveness. The findings have clinical implications for targeted prevention of child anxiety.

8.
J Thromb Haemost ; 18(1): 17-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894660

RESUMO

Hereditary deficiency of antithrombin, a natural anticoagulant, causes a thrombophilia with a high risk for venous thromboembolism. Guidance for laboratory testing to diagnose antithrombin deficiency include the use of an activity assay for initial testing, performing an antigen test and activity-to-antigen ratio when the activity level is low, using pediatric reference ranges until the age of 6 months, excluding acquired causes of low antithrombin (e.g. liver dysfunction, proteinuria, heparin, disseminated intravascular coagulation, thrombosis, surgery) or falsely normal/elevated results (e.g. argatroban, bivalirudin, dabigatran in factor IIa-based assays; rivaroxaban, apixaban, edoxaban, but not betrixaban in Xa-based assays). Molecular testing, if available, may help determine the risk for thrombosis as this might vary among the different mutations. Moreover, it will identify mutations that can be missed by traditional activity assays. Strategies for interpreting laboratory test results are provided.

9.
J Pediatric Infect Dis Soc ; 9(1): 67-70, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30339241

RESUMO

Disease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti-granulocyte macrophage colony-stimulating factor autoantibodies.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Autoanticorpos/sangue , Brônquios/microbiologia , Broncopatias/microbiologia , Cryptococcus gattii/isolamento & purificação , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Meningite Criptocócica/diagnóstico por imagem , Obstrução das Vias Respiratórias/diagnóstico , Animais , Antifúngicos/uso terapêutico , Encéfalo/diagnóstico por imagem , Brônquios/patologia , Broncopatias/diagnóstico , Broncopatias/terapia , Broncoscopia , Criança , Criptococose/complicações , Criptococose/diagnóstico por imagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imagem por Ressonância Magnética , Meningoencefalite/diagnóstico por imagem , Meningoencefalite/microbiologia , Phascolarctidae/microbiologia
10.
Behav Cogn Psychother ; 48(3): 253-267, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31727188

RESUMO

BACKGROUND: Chronic childhood adversity, negative life events, and anxiogenic parenting behaviours have all been implicated in the development and maintenance of childhood anxiety disorders. However, few studies have addressed whether these factors are associated with particular types of childhood anxiety disorders. AIMS: The aims of this study were to investigate whether specific associations were obtained between specific types of childhood anxiety disorder - namely, social anxiety disorder (SOC), separation anxiety disorder (SEP) and generalized anxiety disorder (GAD) - and the nature of particular forms of psycho-social risk - namely, chronic childhood adversity, negative life events, and particular forms of parenting behaviours. METHOD: Two-hundred and ten children (aged 7-12 years) who met diagnostic criteria for SOC, SEP or GAD and their primary caregivers completed questionnaire measures on chronic childhood adversity and negative life events. In addition, dyads participated in two laboratory-based assessments of parent-child interactions. RESULTS: We found little evidence for disorder specificity for chronic childhood adversity and negative life events, except in the case of separation anxiety disorder. Anxious children with separation anxiety were more likely than children with other forms of anxiety disorders to live with a single parent, experience more frequent parent arguments, and more negative life events. No group differences in observed parenting behaviours were found. CONCLUSIONS: Childhood SEP may be particularly associated with family challenges which may need specific consideration to optimize prevention and/or treatment. Beyond this, there is limited evidence of specific associations between family and environmental factors and specific types of childhood anxiety disorders.


Assuntos
Transtornos de Ansiedade , Ansiedade , Ansiedade de Separação , Cuidadores , Criança , Humanos , Acontecimentos que Mudam a Vida , Poder Familiar
11.
Child Dev ; 91(2): e383-e399, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30737957

RESUMO

Interventions that train parents to share picture books with children are seen as a strategy for supporting child language development. We conducted meta-analyses using robust variance estimation modeling on results from 19 RCTs (Ntotal  = 2,594; Mchildage  = 1-6 years). Overall, book-sharing interventions had a small sized effect on both expressive language (d = 0.41) and receptive language (d = 0.26). They had a large effect on caregiver book-sharing competence (d = 1.01). The impact of the intervention on child language was moderated by intervention dosage, with lower dosage associated with a minimal impact. Child age and caregiver education level were unrelated to child outcome. This review and meta-analysis confirms the promise of book-sharing interventions for enhancing and accelerating child language development.

12.
J Child Psychol Psychiatry ; 61(1): 62-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364169

RESUMO

BACKGROUND: This study evaluated whether clinical and economic outcomes from CBT for child anxiety disorders in the context of maternal anxiety disorders are improved by adding treatment focused on (a) maternal anxiety disorders or (b) mother-child interactions. METHODS: Two hundred and eleven children (7-12 years, 85% White British, 52% female) with a primary anxiety disorder, whose mothers also had a current anxiety disorder, were randomised to receive (a) child-focused CBT with nonspecific control interventions (CCBT+Con), (b) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (c) CCBT with an intervention targeting the mother-child interaction (CCBT+MCI). A cost-utility analysis from a societal perspective was conducted using mother/child combined quality-adjusted life years (QALYs). [Trial registration: https://doi.org/10.1186/isrctn19762288]. RESULTS: MCBT was associated with immediate reductions in maternal anxiety compared to the nonspecific control; however, after children had also received CCBT, maternal outcomes in the CCBT+MCI and CCBT+Con arms improved and CCBT+MCBT was no longer superior. Neither CCBT+MCBT nor CCBT+MCI conferred a benefit over CCBT+Con in terms of child anxiety disorder diagnoses post-treatment [primary outcome] (adj RR: 1.22 (95% CI: 0.88, 1.67), p = .23; adj RR: 1.21 (95% CI: 0.88, 1.65), p = .24, respectively) or global improvement ratings (adj RR: 1.25 (95% CI: 0.99, 1.57), p = .06; adj RR: 1.18 (95% CI: 0.93, 1.50), p = .17) or six and 12 months later. No significant differences between the groups were found on the main economic outcome measures (child/mother combined QALY mean difference: CCBT+MCBT vs. CCBT+Con: -0.04 (95% CI: -0.12, 0.04), p = .29; CCBT+MCI vs. CCBT+Con: 0.02 (95% CI: -0.05, -0.09), p = .54). CCBT+MCI was associated with nonsignificantly higher costs than CCBT (mean difference: £154 (95% CI: -£1,239, £1,547), p = .83) but, when taking into account sampling uncertainty, it may be cost-effective compared with CCBT alone. CONCLUSIONS: Good outcomes were achieved for children and their mothers across treatment arms. There was no evidence of significant clinical benefit from supplementing CCBT with either CBT for the maternal anxiety disorder or treatment focussed on mother-child interactions, but the addition of MCI (and not MCBT) may be cost-effective.

13.
BMC Pediatr ; 19(1): 320, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-31493789

RESUMO

BACKGROUND: Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. AIM: This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. METHODS: This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. RESULTS: There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo-ß lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. CONCLUSIONS: There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

14.
Psychol Assess ; 31(8): 1006-1018, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31070449

RESUMO

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preadolescent children. This study aimed to establish the ability of the Spence Children's Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Transtornos de Ansiedade/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Criança , Feminino , Humanos , Masculino , Mães , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Trials ; 20(1): 253, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046826

RESUMO

BACKGROUND: Children in many low- and middle-income countries (LMICs) are at high risk for exposure to violence and later violent behaviour. The World Health Organization has declared an urgent need for the evaluation and implementation of low-cost parenting interventions in LMICs to prevent violence. Two areas of significant early risk are harsh parenting and poor child cognitive and socio-emotional development. Parenting interventions suitable for LMIC contexts have been developed targeting these risk factors and have been shown to have promising effects. However, their impact on child aggression, a key precursor of violence, has yet to be determined. The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) has been designed to address this issue. METHODS: We are conducting a randomised controlled trial to evaluate two early parenting interventions for mothers of children aged between 30 and 42 months in a Brazilian city. The first of these, dialogic book-sharing (DBS), aims to promote child cognitive and socio-emotional development; and the second, the ACT Raising Safe Kids Program (ACT), is designed to reduce harsh parenting. These interventions are being compared with a control group receiving neither intervention. Three hundred and sixty-nine families in a birth cohort are being randomly allocated to one of the three groups (DBS, ACT, Control). Facilitators deliver the interventions to groups of five to 10 mothers at weekly sessions for 8 weeks in DBS and 9 weeks in ACT. Independent assessments of parenting and child development are being made before the interventions, shortly afterwards, and at follow-up 6 months later. The primary outcome is child aggression, and the two main secondary outcomes are: (1) child cognitive and socio-emotional development and (2) harsh parenting. Longer-term outcomes will be investigated as the birth cohort is followed into late childhood, adolescence, and adulthood. DISCUSSION: The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) aims to evaluate the impact of two early parenting interventions on child aggression and several other key risk factors for the development of violence, including aspects of parenting and child cognition and socio-emotional functioning. The study is being carried out in a LMIC context where violence constitutes a major social and health burden. Since the two interventions are brief and, with modest levels of training, readily deliverable in LMIC settings, a demonstration that they benefit parenting and reduce risk factors for violence would be of major significance. TRIAL REGISTRATION: Brazilian Ministry of Health Register of Clinical Trials, ID: RBR-2kwfsk . Registered on 6 June 2018.


Assuntos
Agressão , Comportamento Infantil , Desenvolvimento Infantil , Educação não Profissionalizante/métodos , Relações Mãe-Filho , Mães/educação , Poder Familiar/psicologia , Violência/prevenção & controle , Fatores Etários , Brasil , Pré-Escolar , Cognição , Emoções , Feminino , Humanos , Masculino , Mães/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento Social , Fatores de Tempo , Resultado do Tratamento , Violência/psicologia
16.
Transl Psychiatry ; 9(1): 150, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123309

RESUMO

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/estatística & dados numéricos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Criança , Humanos
17.
Front Chem ; 7: 287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106198

RESUMO

Titanium is a strong, corrosion-resistant light-weight metal which is poised to replace steel in automobiles, aircraft, and watercraft. However, the titanium oxide (titania) layer that forms on the surface of titanium in air is notoriously difficult to lubricate with conventional lubricants, which restricts its use in moving parts such as bearings. Ionic liquids (ILs) are potentially excellent lubricants for titania but the relationship between IL molecular structure and lubricity for titania remains poorly understood. Here, three-ball-on-disk macrotribology and atomic force microscopy (AFM) nanotribology measurements reveal the lubricity of four IL lubricants: trioctyl(2-ethylhexyl)phosphonium bis(2-ethylhexyl)phosphate (P8,8,8,6(2) BEHP), trihexyl(tetradecyl)phosphonium bis(2-ethylhexyl)phosphate (P6,6,6,14 BEHP), trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate (P6,6,6,14 ( i C8)2PO2), and trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide (P6,6,6,14 TFSI). The macrotribology measurements demonstrated that friction decreased in P6,6,6,14 TFSI by four times (µ = 0.13) compared to in hexadecane, even at 60°C and loads up to 10 N. On the other hand, P8,8,8,6(2) BEHP reduced friction most effectively in the AFM nanotribology measurements. The results were interpreted in terms of the lubrication regime. The lower viscosity of P6,6,6,14 TFSI coupled with its good boundary lubrication made it the most effective IL for the macrotribology measurements, which were in the mixed lubrication regime. Conversely, the cation structure of P8,8,8,6(2) BEHP allowed it to adsorb strongly to the surface and minimized energy dissipation in the nanotribology measurements, although its high bulk viscosity inhibited its performance in the mixed regime. These results reinforce the importance of carefully selecting IL lubricants based on the lubrication regime of the sliding surfaces.

19.
Blood Cells Mol Dis ; 78: 14-21, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-27499018

RESUMO

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187.


Assuntos
Terapia de Reposição de Enzimas , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Adulto , Idoso , Biomarcadores , Terapia de Reposição de Enzimas/métodos , Feminino , Doença de Gaucher/sangue , Doença de Gaucher/diagnóstico , Glucosilceramidase/administração & dosagem , Glucosilceramidase/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
20.
Clin Genitourin Cancer ; 17(2): e247-e257, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30579699

RESUMO

BACKGROUND: Procoagulant activity attributed to tissue factor (TF, CD142) bound to lipid microvesicles has previously been shown to be elevated in urine of patients with various solid cancers. The phosphorylation of the C-terminal signal transduction peptide (STP) at Ser253 and Ser258 has been determined to be important for the formation of TF-microvesicles. The purpose of this work was to investigate the marker potential of the TF-STP domain in urine of patients with cancer using immunologic methods to quantitate unphosphorylated TF and TF phosphorylated at Ser253 and Ser258. MATERIALS AND METHODS: We developed monoclonal and polyclonal antibodies directed against the 3 C-terminal STP species of TF and constructed 3 enzyme-linked immunosorbent assays (ELISAs) that specifically recognize unphosphorylated TF and TF phosphorylated at either Ser253 or Ser258. As proof of principle, a preliminary pilot study with stored Biobank-sourced urinary specimens from 45 healthy individuals and 38 patients with bladder cancer were studied using these ELISAs. RESULTS: We report that all 3 species of TF were found in the urine. Two species, TF-pSer258 and unphosphorylated TF, were significantly elevated in the cohort with bladder cancer. The sensitivity of TF-pSer258 by the receiver operator characteristic technique was 86.8%, with a specificity of 97.8% at a cutoff value of 0.55 ng/mL. Using a simplified sample preparation method for the ELISAs on the same clinical specimens, the sensitivity of TF-pSer258 was 86.8%, with a specificity of 93.3% at a cutoff value of 0.53 ng/mL. The unphosphorylated TF species was significantly elevated in later stage bladder cancer with best results seen for the unfractionated preparation technique (95% confidence interval, 10.55-15.74; N = 20) but not early stage non-muscle-invasive bladder cancer (95% confidence interval, 4.71-10.73; N = 18; P < .02). CONCLUSIONS: The development of these new ELISAs allows the quantitation of the urinary biomarkers TF-pSer258 and unphosphorylated TF, which may lead to a new diagnostic approach to the early detection of bladder cancer and warrant further investigation in a prospective trial.


Assuntos
Biomarcadores Tumorais/urina , Serina/metabolismo , Tromboplastina/urina , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/química , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Fosforilação , Projetos Piloto , Estudos Prospectivos , Sinais Direcionadores de Proteínas , Tromboplastina/química , Neoplasias da Bexiga Urinária/patologia
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