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1.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34711679

RESUMO

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.


Assuntos
Pesquisa Empírica , Reprodutibilidade dos Testes , Insegurança Alimentar , Humanos , Medição da Dor , Projetos de Pesquisa , Alocação de Recursos
2.
J Biol Chem ; 298(5): 101899, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35398354

RESUMO

The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration of the cerebellum that results in movement disorder. Recently, a new heritable form of SCA, spinocerebellar ataxia type 48 (SCA48), was attributed to dominant mutations in STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these mutations cause SCA48. STUB1 encodes for the protein C terminus of Hsc70 interacting protein (CHIP), an E3 ubiquitin ligase. CHIP is known to regulate proteostasis by recruiting chaperones via a N-terminal tetratricopeptide repeat domain and recruiting E2 ubiquitin-conjugating enzymes via a C-terminal U-box domain. These interactions allow CHIP to mediate the ubiquitination of chaperone-bound, misfolded proteins to promote their degradation via the proteasome. Here we have identified a novel, de novo mutation in STUB1 in a patient with SCA48 encoding for an A52G point mutation in the tetratricopeptide repeat domain of CHIP. Utilizing an array of biophysical, biochemical, and cellular assays, we demonstrate that the CHIPA52G point mutant retains E3-ligase activity but has decreased affinity for chaperones. We further show that this mutant decreases cellular fitness in response to certain cellular stressors and induces neurodegeneration in a transgenic Caenorhabditis elegans model of SCA48. Together, our data identify the A52G mutant as a cause of SCA48 and provide molecular insight into how mutations in STUB1 cause SCA48.


Assuntos
Ataxias Espinocerebelares , Ubiquitina-Proteína Ligases , Ubiquitina , Humanos , Mutação , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
3.
J Urol ; 207(3): 573-580, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34694140

RESUMO

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) is recommended for staging of prostate cancer, but its additional benefit above mpMRI alone in local evaluation for prostate cancer is unclear. The study aim was to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot-assisted laparoscopic radical prostatectomy (RALP) histology. MATERIALS AND METHODS: We retrospectively reviewed 1,123 men with a preoperative mpMRI and 68Ga-PSMA PET/CT prior to a RALP. Tumor locations were collected from both imaging modalities and compared to totally embedded prostate histology. Lowest apparent diffusion coefficient value on mpMRI and the highest maximum standardized uptake value (SUVmax) on 68Ga-PSMA PET/CT were collected on the index lesions to perform analysis on detection rates. RESULTS: Median prostate specific antigen was 6. Median Gleason score on biopsy and RALP histology was 4+3. The index lesion and multifocal tumor detection were similar between mpMRI and 68Ga-PSMA PET/CT (p=0.10; p=0.11). When combining mpMRI and 68Ga-PSMA PET/CT, index Gleason score ≥3+4 cancer at RALP was identified in 92%. Only 10% of patients with Gleason score ≤3+4 on biopsy with an SUVmax <5 were upgraded to ≥4+3 on RALP histology, compared to 90% if the SUVmax was >11. CONCLUSIONS: The addition of a diagnostic 68Ga-PSMA PET/CT to mpMRI can improve the detection of significant prostate cancer and improve the ability to identify men suitable for active surveillance.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/sangue , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/cirurgia , Radioisótopos , Estudos Retrospectivos
4.
Psychol Sci ; 33(6): 889-905, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35482995

RESUMO

Although White Americans increasingly express egalitarian views, how they express egalitarianism may reveal inegalitarian tendencies and sow mistrust with Black Americans. In the present experiments, Black perceivers inferred likability and trustworthiness and accurately inferred underlying racial attitudes and motivations from White writers' declarations that they are nonprejudiced and egalitarian (Experiments 1 and 2). White writers believed that their egalitarianism seemed more inoffensive and indicative of allyship than was perceived by Black Americans (Experiment 1a). Linguistic analysis revealed that, when inferring racial attitudes and motivations, Black perceivers accurately attended to language emphasizing humanization, support for equal opportunity, personal responsibility, and the idea that equality already exists (Experiment 1b). We found causal evidence that these linguistic cues informed Black Americans' perceptions of White egalitarians (Experiment 2). Suggesting societal costs of these perceptions, White egalitarians' underlying racial beliefs negatively predicted Black participants' actual trust and cooperation in an economic game (Experiment 3). Our experiments (N = 1,335 adults) showed that White Americans' insistence that they are egalitarian itself perpetuates mistrust with Black Americans.


Assuntos
Negro ou Afro-Americano , Confiança , População Negra , Humanos , Preconceito , População Branca
5.
J Public Health (Oxf) ; 44(4): 851-862, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121114

RESUMO

BACKGROUND: Brief advice is recommended to increase physical activity (PA) within primary care. This study assessed change in PA levels and mental well-being after a motivational interviewing (MI) community-based PA intervention and the impact of signposting (SP) and social action (SA) (i.e. weekly group support) pathways. METHODS: Participants (n = 2084) took part in a community-based, primary care PA programme using MI techniques. Self-reported PA and mental well-being data were collected at baseline (following an initial 30-min MI appointment), 12 weeks, 6 months and 12 months. Participants were assigned based upon the surgery they attended to the SP or SA pathway. Multilevel models derived point estimates and 95% confidence intervals for outcomes at each time point and change scores. RESULTS: Participants increased PA and mental well-being at each follow-up time point through both participant pathways and with little difference between pathways. Retention was similar between pathways at 12 weeks, but the SP pathway retained more participants at 6 and 12 months. CONCLUSIONS: Both pathways produced similar improvements in PA and mental well-being; however, the addition of a control would have provided further insight as to the effectiveness. Due to lower resources yet similar effects, the SP pathway could be incorporated to support PA in primary care settings.


Assuntos
Entrevista Motivacional , Humanos , Exercício Físico , Saúde Mental , Autorrelato
6.
Community Dent Health ; 39(3): 181-186, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35605141

RESUMO

INTRODUCTION: Oral health inequalities existed before Covid, but the pandemic presented an unprecedented challenge for health services. Our aim was to determine whether patient groups at risk of health care inequality due to the pandemic could be identified from NHS dental claims. METHODS: Secondary analysis of routinely collected NHS Business Services Authority data for patients treated by General Dental Practitioners in England and Wales between April 2019 and January 2022 to assess the effect of the Covid pandemic on claims for patients attending general dental practices. Data for treatment items claimed after the start of the first lockdown were compared to the pre-lockdown period. RESULTS: The proportion of claims for child fillings, child extractions and child fluoride varnish application after March 2020 were lower than equivalent proportions for adults, in both England and Wales. Similarly, there were consistently fewer claims for fillings and extractions for patients claiming pension credit guarantee credit than all pensioners in both England and Wales. CONCLUSION: The Covid pandemic may have caused health care inequality for children and patients claiming pension credit guarantee credit. This may compound the inequality in oral health for these patients.


Assuntos
COVID-19 , Odontologia Estatal , Adulto , Criança , Controle de Doenças Transmissíveis , Odontólogos , Disparidades em Assistência à Saúde , Humanos , Pandemias/prevenção & controle , Papel Profissional , Medicina Estatal
7.
Pancreatology ; 20(3): 394-408, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32173257

RESUMO

BACKGROUND: Death from pancreatic ductal adenocarcinoma (PDAC) is rising across the world and PDAC is predicted to be the second most common cause of cancer death in the USA by 2030. Development of effective biotherapies for PDAC are hampered by late presentation, a low number of differentially expressed molecular targets and a tumor-promoting microenvironment that forms both a physical, collagen-rich barrier and is also immunosuppressive. In 2017 Pancreatic Cancer UK awarded its first Grand Challenge Programme award to tackle this problem. The team plan to combine the use of novel CAR T cells with strategies to overcome the barriers presented by the tumor microenvironment. In advance of publication of those data this review seeks to highlight the key problems in effective CAR T cell therapy of PDAC and to describe pre-clinical and clinical progress in CAR T bio-therapeutics.


Assuntos
Carcinoma Ductal Pancreático/genética , Perfilação da Expressão Gênica , Neoplasias Pancreáticas/genética , Humanos , Imunoterapia Adotiva , Masculino , Pessoa de Meia-Idade , Reino Unido
8.
Healthc Manage Forum ; 32(2): 92-96, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30700152

RESUMO

Niagara Health, a multi-site hospital organization, has developed a multimodal, comprehensive strategy to manage patients with a Difficult Airway (DA) in a non-operative setting. The Difficult Airway Pathway (DAP) is an evidence-based strategy aimed to train staff to reduce critical events. The DAP initiative aligns with the LEADS framework for change management and includes an annual review of reported critical incidents and an Enterprise Risk Management (ERM) Assessment Summary, with the goal to "create a regional systematic approach to support personnel, equipment and education." The guiding vision is: "Right people, Right equipment, Right timing: No failed airway." Preliminary evaluation suggests the strategy reduces morbidity and mortality of difficulty airway incidents outside the operating room.


Assuntos
Manuseio das Vias Aéreas/métodos , Procedimentos Clínicos , Liderança , Gestão de Riscos/métodos , Manuseio das Vias Aéreas/efeitos adversos , Algoritmos , Competência Clínica , Educação Médica Continuada , Humanos , Avaliação das Necessidades , Ontário , Avaliação de Programas e Projetos de Saúde
9.
Ann Oncol ; 29(2): 466-471, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29145573

RESUMO

Background: Inverted sinonasal (Schneiderian) papilloma (ISP) is a locally aggressive neoplasm often associated with sinonasal squamous cell carcinoma (SNSCC). While the etiology of ISP is not well understood, human papillomavirus (HPV) has been detected in a subset of cases. Our group recently identified activating somatic EGFR mutations in the majority of ISP and ISP-associated SNSCC. However, the relationship between EGFR mutations and HPV infection has not been explored. Patients and methods: We evaluated 58 ISP and 22 ISP-associated SNSCC (including 13 patients with matched ISP/SNSCC samples), as well as 14 SNSCC without clinical or pathologic evidence of an associated ISP. Formalin-fixed, paraffin-embedded samples were evaluated for EGFR mutations using Sanger sequencing and for HPV infection using GP5+/GP6+ PCR. HPV subtyping based on the L1 sequence was done for HPV positive cases including temporally distinct tumors for four patients. Clinicopathologic data including progression free survival was also analyzed. Results: All ISP and ISP-associated SNSCC demonstrated either an EGFR mutation or HPV infection. HPV and EGFR mutation were mutually exclusive in all cases of ISP-associated SNSCC and all but one ISP; this case was only weakly HPV positive, and analysis of a prior temporally distinct ISP specimen from this patient failed to show HPV infection, suggesting transient infection/incidental colonization. HPV subtypes in ISP and ISP-associated SNSCC were predominantly low-risk, in contrast with SNSCC without ISP association, which showed frequent high-risk HPV. All paired ISP and associated SNSCC samples demonstrated concordant HPV status and EGFR genotypes. ISP progression to SNSCC was significantly associated with the presence of HPV infection and the absence of an EGFR mutation (log-rank = 9.620, P = 0.002). Conclusions: Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.


Assuntos
Neoplasias Primárias Múltiplas/etiologia , Papiloma Invertido/etiologia , Infecções por Papillomavirus/complicações , Neoplasias dos Seios Paranasais/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Genes erbB-1 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Seios Paranasais , Estudos Retrospectivos
10.
Nutr Metab Cardiovasc Dis ; 28(6): 582-591, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29691148

RESUMO

BACKGROUND AND AIMS: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD. METHODS AND RESULTS: HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA. CONCLUSION: Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , HDL-Colesterol/sangue , Falência Renal Crônica/terapia , Ramipril/uso terapêutico , Diálise Renal , Valsartana/uso terapêutico , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Ramipril/efeitos adversos , Diálise Renal/efeitos adversos , Tennessee , Fatores de Tempo , Resultado do Tratamento , Valsartana/efeitos adversos
11.
Scand J Med Sci Sports ; 28(10): 2123-2134, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29790207

RESUMO

Changes in muscle fascicle mechanics have been postulated to underpin the repeated bout effect (RBE) observed following exercise-induced muscle damage (EIMD). However, in the medial gastrocnemius (MG), mixed evidence exists on whether fascicle stretch amplitude influences the level of EIMD, thus questioning whether changes in fascicle mechanics underpin the RBE. An alternative hypothesis is that neural adaptations contribute to the RBE in this muscle. The aim of this study was to investigate the neuromechanical adaptations during and after repeated bouts of a highly controlled muscle lengthening exercise that aimed to maximize EIMD in MG. In all, 20 subjects performed two bouts of 500 active lengthening contractions (70% of maximal activation) of the triceps surae, separated by 7 days. Ultrasound constructed fascicle length-torque (L-T) curves of MG, surface electromyography (EMG), maximum torque production, and muscle soreness were assessed before, 2 hours and 2 days after each exercise bout. The drop in maximum torque (4%) and the increase in muscle soreness (24%) following the repeated bout were significantly less than following the initial bout (8% and 59%, respectively), indicating a RBE. However, neither shift in the L-T curve nor changes in EMG parameters were present. Furthermore, muscle properties during the exercise were not related to the EIMD or RBE. Our results show that there are no global changes in gastrocnemius mechanical behavior or neural activation that could explain the observed RBE in this muscle. We suggest that adaptations in the non-contractile elements of the muscle are likely to explain the RBE in the triceps surae.


Assuntos
Adaptação Fisiológica , Exercício Físico/fisiologia , Contração Muscular , Músculo Esquelético/fisiologia , Adulto , Fenômenos Biomecânicos , Eletromiografia , Feminino , Humanos , Masculino , Mialgia , Torque , Ultrassonografia , Adulto Jovem
12.
BMC Pediatr ; 18(1): 44, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426307

RESUMO

BACKGROUND: The World Health Organization (WHO) recommends rapid intravenous rehydration, using fluid volumes of 70-100mls/kg over 3-6 h, with some of the initial volume given rapidly as initial fluid boluses to treat hypovolaemic shock for children with acute gastroenteritis (AGE) and severe dehydration. The evidence supporting the safety and efficacy of rapid versus slower rehydration remains uncertain. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) on 11th of May 2017 comparing different rates of intravenous fluid therapy in children with AGE and moderate or severe dehydration, using standard search terms. Two authors independently assessed trial quality and extracted data. Non-RCTs and non-English articles were excluded. The primary endpoint was mortality and secondary endpoints included adverse events (safety) and treatment efficacy. MAIN RESULTS: Of the 1390 studies initially identified, 18 were assessed for eligibility. Of these, 3 studies (n = 464) fulfilled a priori criteria for inclusion; most studied children with moderate dehydration and none were conducted in resource-poor settings. Volumes and rates of fluid replacement varied from 20 to 60 ml/kg given over 1-2 h (fast) versus 2-4 h (slow). There was substantial heterogeneity in methodology between the studies with only one adjudicated to be of high quality. There were no deaths in any study. Safety endpoints only identified oedema (n = 6) and dysnatraemia (n = 2). Pooled analysis showed no significant difference between the rapid and slow intravenous rehydration groups for the proportion of treatment failures (N = 468): pooled RR 1.30 (95% CI: 0.87, 1.93) and the readmission rates (N = 439): pooled RR 1.39 (95% CI: 0.68, 2.85). CONCLUSIONS: Despite wide implementation of WHO Plan C guideline for severe AGE, we found no clinical evaluation in resource-limited settings, and only limited evaluation of the rate and volume of rehydration in other parts of the world. Recent concerns over aggressive fluid expansion warrants further research to inform guidelines on rates of intravenous rehydration therapy for severe AGE.


Assuntos
Desidratação/terapia , Hidratação/métodos , Gastroenterite/complicações , Doença Aguda , Adolescente , Criança , Pré-Escolar , Desidratação/etiologia , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Fatores de Tempo , Resultado do Tratamento
13.
Water Sci Technol ; 78(1-2): 165-173, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30101799

RESUMO

Microalgae commonly found in waste stabilization ponds (WSPs) are able to accumulate elevated phosphorus levels within their cells in a process known as luxury uptake. However, there are few studies focused on luxury uptake in full scale WSPs. In order to comprehensively quantify the occurrence of this phenomenon, eight different WSP sites comprising seven primary facultative, six maturation and two high rate algal ponds (HRAPs) spread over several climatic regions were monitored over four seasons. Of the 15 ponds studied, 13 of these exhibited elevated levels of biomass phosphorus content at some point; however, the occurrence in HRAPs was limited. More than half of the samples tested had elevated phosphorus contents and this occurred in all climatic zones surveyed. The phosphorus content of the biomass was significantly correlated to decreasing rainfall and increasing total dissolved phosphorus. Microscopic analysis revealed that nearly all the 17 microalgal and five cyanobacterial genera identified performed luxury uptake, but at varying frequencies. This is the first time that the genera of algae responsible for luxury uptake in full scale WSPs has been studied. Chlamydomonas/Cryptomonas, Micractinium/Microcystis and Scenedesmus were the only microalgal genera found to both commonly occur in WSPs and consistently perform luxury uptake.


Assuntos
Microalgas , Fósforo , Lagoas/química , Eliminação de Resíduos Líquidos/métodos , Biodegradação Ambiental , Clorófitas/química , Clorófitas/metabolismo , Microalgas/química , Microalgas/metabolismo , Fósforo/química , Fósforo/isolamento & purificação , Fósforo/metabolismo , Estações do Ano , Águas Residuárias/química
14.
Br J Biomed Sci ; 74(3): 110-120, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28625099

RESUMO

In recent years, there have been a number of significant developments in toxicology within clinical laboratories, both with the available instrumentation and in the range of compounds abused by the drug using communities. There have also been developments in the regulation of forensic science in the UK which may in time impact clinical toxicology. This review is designed to provide an update of these changes within toxicology to the more general pathology laboratory audience. For detailed information in specific areas, the reader is referred to the references in the text. In the preparation of this review, the references held by the author as part of his practice of an analytical toxicologist in the NHS were supplemented by a full literature search in Medline and Embase and a review of pertinent UK and European Governments and regulatory agency websites for recent documentation.


Assuntos
Técnicas de Laboratório Clínico , Toxicologia , Ciências Forenses , Humanos , Imunoensaio , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
15.
Child Care Health Dev ; 43(4): 577-587, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28480514

RESUMO

BACKGROUND: Undernutrition contributes to at least half the estimated six million annual childhood deaths worldwide. Furthermore, one in three children fails to meet their developmental potential because of risks including stunting, illness, under-stimulation, poor responsive interactions and maternal depressive symptoms. Our study investigates the role of caregiving processes on children's height-for-age at 2 and 4 years. METHODS: The Pakistan Early Child Development Scale-up study assessed the longitudinal effectiveness of early nutrition and responsive stimulation interventions on growth and development at 4 years of age. In total, 1302 children were followed up from birth to 4 years. We leveraged path analyses to explore potential mediators of early intervention effects on children's height-for-age at 4 years, including maternal depressive symptoms, mother-child interaction quality, diarrhoeal illness and height-for-age at 2 years. RESULTS: Our final model had excellent model fit (comparative fix index = 0.999, Tucker-Lewis index = 0.998, root mean square error of approximation = 0.008) and showed that mother-child interaction quality mediated the effects of both enhanced nutrition and responsive stimulation interventions on height-for-age at 4 years via its longitudinal stability from 2 years of age (ß = 0.016, p = 0.005; ß = 0.048, p < 0.001, respectively). Further, diarrhoeal illness mediated the effects of maternal depressive symptoms at 1 year post partum on children's height-for-age at 4 years via the longitudinal stability of height-for-age z-score from 2 years of age onwards (ß = -0.007, p = 0.019). CONCLUSIONS: The quality of early caregiving experience mediated the association between both interventions and height-for-age. The effect of maternal depressive symptoms on growth was mediated by diarrhoeal illness. Programmatic approaches to child nutrition and growth must address all these potentially modifiable factors.


Assuntos
Desenvolvimento Infantil , Intervenção Educacional Precoce , Transtornos do Crescimento , Promoção da Saúde/organização & administração , Relações Mãe-Filho , Mães , Estatura , Desenvolvimento Infantil/fisiologia , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Diarreia/complicações , Diarreia/epidemiologia , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Longitudinais , Masculino , Relações Mãe-Filho/psicologia , Mães/educação , Estado Nutricional , Paquistão , Pobreza
16.
Paediatr Child Health ; 22(5): 249-254, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29479228

RESUMO

OBJECTIVES: To compare short- and long-term neurodevelopmental outcomes at 3 years of corrected age of preterm infants cared for by 24-hour in-house staff neonatologists and those cared for by staff neonatologists during daytime only. METHODS: Retrospective analysis of prospectively collected follow-up data on all nonanomalous preterm infants from 1998 to 2004 excluding year 2001 as a washout period. Infants were divided into two groups based on care provided by staff neonatologists: 24-hour in-house coverage (24-hour coverage 1998-2000) and daytime coverage (day coverage 2002-2004). Short- and long-term outcomes were compared. RESULTS: A total of 387 (78%) of the screened infants were included. Twenty-four-hour coverage (n=179) and day coverage (n=208) groups had a median birth weight (BW) of 875 g (range 470-1250) and 922 g (480-1530; P=0.028), respectively, and both had a median gestational age of 27 weeks. In the day coverage group, a smaller proportion of mothers had chorioamnionitis (20% vs. 30%; P=0.025), received less antibiotics (62% vs. 73%; P=0.023), and infants had fewer cases of confirmed sepsis (14% vs. 23%; P=0.022). In the day coverage group, a larger number of infants had respiratory distress syndrome (87% vs. 77%; P=0.011) and required prolonged mechanical ventilation (median 31 vs. 21 days; P=0.002). The incidence of major neurodevelopmental impairment was not significantly different between the two groups (odds ratio 0.76; 95% confidence interval 0.34-1.65). CONCLUSIONS: Duration of mechanical ventilation was reduced with 24-hour in-house coverage by staff neonatologists. However, 24-hour coverage was not associated with any difference in neurodevelopmental (ND) outcomes at 3-year corrected age.

17.
Clin Genet ; 89(1): 115-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25810209

RESUMO

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Histona-Lisina N-Metiltransferase/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Fenótipo , Criança , Pré-Escolar , Exoma , Feminino , Loci Gênicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino
18.
Allergy ; 71(5): 701-10, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27111273

RESUMO

BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.


Assuntos
Suplementos Nutricionais , Eczema/prevenção & controle , Fórmulas Infantis , Leite/imunologia , Prebióticos/administração & dosagem , Adulto , Alérgenos/imunologia , Animais , Biomarcadores , Bovinos , Citocinas , Eczema/epidemiologia , Eczema/etiologia , Feminino , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Hipersensibilidade a Leite/epidemiologia , Hipersensibilidade a Leite/prevenção & controle , Fatores de Risco
19.
Scand J Med Sci Sports ; 26(7): 774-81, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26103786

RESUMO

Generating high leg power outputs is important for executing rapid movements. Squats are commonly used to increase leg strength and power. Therefore, it is useful to understand factors affecting power output in squatting. We aimed to deconstruct the mechanisms behind why power is maximized at certain resistances in squatting. Ten male rowers (age = 20 ± 2.2 years; height = 1.82 ± 0.03 m; mass = 86 ± 11 kg) performed maximal power squats with resistances ranging from body weight to 80% of their one repetition maximum (1RM). Three-dimensional kinematics was combined with ground reaction force (GRF) data in an inverse dynamics analysis to calculate leg joint moments and powers. System center of mass (COM) velocity and power were computed from GRF data. COM power was maximized across a range of resistances from 40% to 60% 1RM. This range was identified because a trade-off in hip and knee joint powers existed across this range, with maximal knee joint power occurring at 40% 1RM and maximal hip joint power at 60% 1RM. A non-linear system force-velocity relationship was observed that dictated large reductions in COM power below 20% 1RM and above 60% 1RM. These reductions were due to constraints on the control of the movement.


Assuntos
Articulação do Quadril/fisiologia , Articulação do Joelho/fisiologia , Movimento/fisiologia , Força Muscular/fisiologia , Adolescente , Fenômenos Biomecânicos , Humanos , Masculino , Adulto Jovem
20.
J Environ Manage ; 183: 280-293, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27600332

RESUMO

Marine Protected Areas (MPAs), marine areas in which human activities are restricted, are implemented worldwide to protect the marine environment. However, with a large proportion of these MPAs being no more than paper parks, it is important to be able to evaluate MPA success, determined by improvements to biophysical, socio-economic and governance conditions. In this study a systematic literature review was conducted to determine the most frequently used indicators of MPA success. These were then applied to a case study to demonstrate how success can be evaluated. The fifteen most frequently used indicators included species abundance, level of stakeholder participation and the existence of a decision-making and management body. Using the indicator framework with a traffic light system, we demonstrate how an MPA can be evaluated in terms of how well it performs against the indicators using secondary data from the literature. The framework can be used flexibly. For example, where no MPA data currently exist, the framework can be populated by qualitative data provided by local stakeholder knowledge. This system provides a cost-effective and straightforward method for managers and decision-makers to determine the level of success of any MPA and identify areas of weakness. However, given the variety of motivations for MPA establishment, this success needs to be determined in the context of the original management objectives of the MPA with greater weighting being placed on those objectives where appropriate.


Assuntos
Conservação dos Recursos Naturais/métodos , Ecossistema , Fenômenos Biofísicos , Análise Custo-Benefício , Bases de Dados Factuais , Tomada de Decisões , Inglaterra , Oceanos e Mares , Fatores Socioeconômicos
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