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1.
PLoS Comput Biol ; 20(1): e1011783, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206969

RESUMO

Neurons throughout the brain modulate their firing rate lawfully in response to sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization in which neurons aim to robustly and efficiently represent sensory information. Our understanding of how this optimization varies across different areas in the brain, however, is still in its infancy. Here, we show that neural sensory responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation towards optimizing for perceptual discrimination. Focusing on the representation of binocular disparities-the slight differences in the retinal images of the two eyes-we re-analyze measurements characterizing neuronal tuning curves in brain areas V1, V2, and MT (middle temporal) in the macaque monkey. We compare these to measurements of the statistics of binocular disparity typically encountered during natural behaviors using a Fisher Information framework. The differences in tuning curve characteristics across areas are consistent with a shift in optimization goals: V1 and V2 population-level responses are more consistent with maximizing the information encoded about naturally occurring binocular disparities, while MT responses shift towards maximizing the ability to support disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective areas of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings emphasize the need to consider not just information preservation and neural resources, but also relevance to behavior, when assessing the optimality of neural codes.


Assuntos
Córtex Visual , Animais , Córtex Visual/fisiologia , Macaca , Disparidade Visual , Encéfalo , Neurônios/fisiologia , Estimulação Luminosa/métodos
2.
J Am Chem Soc ; 146(19): 13558-13570, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712910

RESUMO

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is used as a ligation tool throughout chemical and biological sciences. Despite the pervasiveness of CuAAC, there is a need to develop more efficient methods to form 1,4-triazole ligated products with low loadings of Cu. In this paper, we disclose a mechanistic model for the ynamine-azide (3 + 2) cycloadditions catalyzed by copper(II) acetate. Using multinuclear nuclear magnetic resonance spectroscopy, electron paramagnetic resonance spectroscopy, and high-performance liquid chromatography analyses, a dual catalytic cycle is identified. First, the formation of a diyne species via Glaser-Hay coupling of a terminal ynamine forms a Cu(I) species competent to catalyze an ynamine-azide (3 + 2) cycloaddition. Second, the benzimidazole unit of the ynamine structure has multiple roles: assisting C-H activation, Cu coordination, and the formation of a postreaction resting state Cu complex after completion of the (3 + 2) cycloaddition. Finally, reactivation of the Cu resting state complex is shown by the addition of isotopically labeled ynamine and azide substrates to form a labeled 1,4-triazole product. This work provides a mechanistic basis for the use of mixed valency binuclear catalytic Cu species in conjunction with Cu-coordinating alkynes to afford superior reactivity in CuAAC reactions. Additionally, these data show how the CuAAC reaction kinetics can be modulated by changes to the alkyne substrate, which then has a predictable effect on the reaction mechanism.

3.
Opt Express ; 32(7): 10761-10776, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570942

RESUMO

Hyperspectral cameras face challenging spatial-spectral resolution trade-offs and are more affected by shot noise than RGB photos taken over the same total exposure time. Here, we present a colorization algorithm to reconstruct hyperspectral images from a grayscale guide image and spatially sparse spectral clues. We demonstrate that our algorithm generalizes to varying spectral dimensions for hyperspectral images, and show that colorizing in a low-rank space reduces compute time and the impact of shot noise. To enhance robustness, we incorporate guided sampling, edge-aware filtering, and dimensionality estimation techniques. Our method surpasses previous algorithms in various performance metrics, including SSIM, PSNR, GFC, and EMD, which we analyze as metrics for characterizing hyperspectral image quality. Collectively, these findings provide a promising avenue for overcoming the time-space-wavelength resolution trade-off by reconstructing a dense hyperspectral image from samples obtained by whisk or push broom scanners, as well as hybrid spatial-spectral computational imaging systems.

4.
Anal Biochem ; 689: 115498, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38423238

RESUMO

We studied the spectral properties of 4'-6-diamidino-2-phenylindole (DAPI) in poly (vinyl alcohol) (PVA) films. Absorption and fluorescence spectra, emission and excitation spectra, quantum yield, and fluorescence lifetime have been characterized. An efficient room temperature phosphorescence (RTP) of DAPI has been observed with UV and blue light excitations. A few hundred millisecond phosphorescence lifetime enables a gated detection with sufficient background reduction. We found the phosphorescent Quantum Yield of DAPI in PVA Film to be 0.0009.


Assuntos
Indóis , Temperatura , Espectrometria de Fluorescência
5.
Paediatr Respir Rev ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38937210

RESUMO

High Flow Nasal Cannula therapy (HFNC) is a form of respiratory support for bronchiolitis. Recent evidence confirms HFNC reduces the risk of treatment escalation by nearly half (45%) compared to standard oxygen therapy (SOT), although most patients (75%) with mild-moderate respiratory distress manage well on SOT. The majority of children (60%) failing SOT respond well to HFNC making rescue use of HFNC a more cost-effective approach compared to its first-line use. HFNC is compared toCPAP in the setting of moderate to severe bronchiolitis. Patients on HFNC have a slightly elevated risk of treatment failure especially in severe bronchiolitis, but this does not translate to a significant difference in patient or healthcare centred outcomes. HFNC has improved tolerance, a lower complication rate and is more easily available in peripheral hospitals. It is therefore the preferred first line option followed by rescue CPAP. HFNC is clinically effective and safe to use in bronchiolitis of all severities.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38847576

RESUMO

OBJECTIVES: Our aim was to determine the prevalence and explanatory factors associated with outcomes in children with acute liver failure (ALF) admitted to the PICU, who also develop severe acute kidney injury (AKI). DESIGN: Retrospective cohort, 2003 to 2017. SETTING: Sixteen-bed PICU in a university-affiliated tertiary care hospital. PATIENTS: Admissions to the PICU with ALF underwent data review of the first week and at least 90-day follow-up. Patients with stages 2-3 AKI using the British Association of pediatric Nephrology definitions, or receiving continuous renal replacement therapy (CRRT) for renal indications, were defined as severe AKI. We excluded ALF cases on CRRT for hepatic-only indications. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, proportion with severe AKI, illness severity and interventions, and outcomes (i.e., transplant, survival with native liver, overall survival, duration of PICU stay, and mechanical ventilation).Ninety-four children with ALF admitted to the PICU were included. Over the first week, 29 had severe AKI, and another eight received CRRT for renal/mixed reno-hepatic indications; hence, the total severe AKI cohort was 37 of 94 (39.4%). In a multivariable logistic regression model, peak aspartate aminotransferase (AST) and requirement for inotropes on arrival were associated with severe AKI. Severe AKI was associated with longer PICU stay and duration of ventilation, and lower spontaneous survival with native liver. In another model, severe AKI was associated with greater odds of mortality (odds ratio 7.34 [95% CI, 1.90-28.28], p = 0.004). After 90 days, 3 of 17 survivors of severe AKI had serum creatinine greater than the upper limit of normal for age. CONCLUSIONS: Many children with ALF in the PICU develop severe AKI. Severe AKI is associated with the timecourse of PICU admission and outcome, including survival with native liver. Future work should look at ALF goal directed renoprotective strategies at the time of presentation.

7.
Pediatr Crit Care Med ; 25(1): 15-23, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38169336

RESUMO

OBJECTIVES: Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. DESIGN: Single-center, retrospective study, 2010-2019. SETTING: Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. PATIENTS: Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. CONCLUSIONS: Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Hipotensão , Hepatopatias , Humanos , Criança , Anticoagulantes/efeitos adversos , Terapia de Substituição Renal Contínua/efeitos adversos , Epoprostenol/efeitos adversos , Estudos Retrospectivos , Estado Terminal/terapia , Terapia de Substituição Renal/métodos , Heparina/uso terapêutico , Ácido Cítrico/uso terapêutico , Hemorragia/etiologia , Hipotensão/induzido quimicamente , Injúria Renal Aguda/etiologia
8.
Eur J Pediatr ; 182(8): 3619-3629, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37233776

RESUMO

Continuous Renal Replacement Therapy (CRRT) machines are used off-label in patients less than 20 kg. Infant and neonates-dedicated CRRT machines are making their way into current practice, but these machines are available only in select centres. This study assesses the safety and efficacy of CRRT using adult CRRT machines in children ≤ 10 kg and to determines the factors affecting the circuit life in these children. DESIGN: Retrospective cohort study of children ≤ 10 kg who received CRRT (January 2010-January 2018) at a PICU in a tertiary care centre in London, UK. Primary diagnosis, markers for illness severity, CRRT characteristics, length of PICU admission and survival to PICU discharge were collected. Descriptive analysis compared survivors and non-survivors. A subgroup analysis compared children ≤ 5 kg to children 5-10 kg. Fifty-one patients ≤ 10 kg received 10,328 h of CRRT, with median weight of 5 kg. 52.94% survived to hospital discharge. Median circuit life was 44 h (IQR 24-68). Bleeding episodes occurred with 6.7% of sessions and hypotension for 11.9%. Analysis of efficacy showed a reduction in fluid overload at 48 h (P = 0.0002) and serum creatinine at 24 and 48 h (P = 0.001). Blood priming was deemed to be safe as serum potassium decreased at 4 h (P = 0.005); there was no significant change in serum calcium. Survivors had a lower PIM2 score at PICU admission (P < 0.001) and had longer PICU length of stay (P < 0.001).    Conclusion: Pending neonatal and infant dedicated CRRT machines, CRRT can be safely and effectively applied to children weighing ≤ 10 kg using adult-sized CRRT machines. WHAT IS KNOWN: • Continuous Renal Replacement Therapy can be used for a variety of renal and non-renal indications to improve outcomes for children in the paediatric intensive care unit. These include, persistent oliguria, fluid overload, hyperkalaemia, metabolic acidosis, hyperlactatemia, hyperammonaemia, and hepatic encephalopathy. • Young children ≤ 10 kg are most often treated using standard adult machines, off-label. This potentially places them at risk of side effects due to high extracorporeal circuit volumes, relatively higher blood flows, and difficulty in achieving vascular access. WHAT IS NEW: • This study found that standard adult machines were effective in reducing fluid overload and creatinine in children ≤ 10 kg. This study also assessed safety of blood priming in this group and found no evidence of an acute fall in haemoglobin or calcium, and a fall in serum potassium by a median of 0.3 mmol/L. The frequency of bleeding episodes was 6.7%, and hypotension requiring vasopressors or fluid resuscitation occurred with 11.9% of treatment sessions. • These findings suggest that adult CRRT machines are sufficiently safe and efficacious for routine use in PICU for children ≤ 10 kg and suggest that further research is undertaken, regarding the routine rollout of dedicated machines.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Lactente , Recém-Nascido , Humanos , Criança , Adulto , Pré-Escolar , Terapia de Substituição Renal Contínua/efeitos adversos , Estudos Retrospectivos , Cálcio , Unidades de Terapia Intensiva Pediátrica
9.
Int J Health Plann Manage ; 38(5): 1360-1376, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37226322

RESUMO

AIM: During humanitarian emergencies, women and children are particularly vulnerable to health complications and neonatal mortality rates have been shown to rise. Additionally, health cluster partners face challenges in coordinating referrals, both between communities and camps to health facilities and across different levels of health facilities. The purpose of this review was to identify the primary referral needs of neonates during humanitarian emergencies, current gaps and barriers, and effective mechanisms for overcoming these barriers. METHODS: A systematic review was performed using four electronic databases (CINAHL, EMBASE, Medline, and Scopus) between June and August 2019 (PROSPERO registration number CRD42019127705). Title, abstract, and full text screening were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The target population was neonates born during humanitarian emergencies. Studies from high-income countries and prior to 1991 were excluded. The STROBE checklist was used to assess for risk of bias. RESULTS: A total of 11 articles were included in the analysis; these were mainly cross-sectional, field-based studies. The primary needs identified were referrals from homes to health facilities before and during labour, and inter-facility referrals after labour to more specialised services. Some of the main barriers included a lack of roads and infrastructure for transport, staff shortages-especially among more specialised services, and a lack of knowledge among patients for self-referral. Mechanisms for addressing these needs and gaps included providing training for community healthcare workers (CHWs) or traditional birth attendants to identify and address antenatal and post-natal complications; education programmes for pregnant women during the antenatal period; and establishing ambulance services in partnership with local Non-Governmental Organizations. CONCLUSION: This review benefited from a strong consensus among selected studies but was limited in the quality of data and types of data that were reported. Based on the above findings, the following recommendations were compiled: Focus on local capacity-building programmes to address programmes acutely. Recruit CHWs to raise awareness of neonatal complications among pregnant women. Upskill CHWs to provide timely, appropriate and quality care during humanitarian emergencies.


Assuntos
Emergências , Socorro em Desastres , Recém-Nascido , Criança , Feminino , Humanos , Gravidez , Estudos Transversais , Instalações de Saúde , Encaminhamento e Consulta
10.
Child Psychiatry Hum Dev ; 54(5): 1438-1445, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35380341

RESUMO

We explored the association between household alcohol use and behavior problems among South-African children, using data from the Asenze study, a population-based cohort of South African children and their caregivers. Household alcohol use and child behavior were assessed when children were 6-8 years old. To examine the association, we performed linear regressions. The sample included 1383 children with complete data under the care of 1251 adults. Children living in a household where self-reported caregiver alcohol use was scored as hazardous (4.6%) had higher levels of problem behavior (ß = 1.94, 95% CI 0.06-3.82). There were no statistically significant associations between reported hazardous alcohol use by another member of the household (14.5%) and child problem behavior. Hazardous household alcohol use was associated with child problem behavior and this effect appeared to be mainly driven by primary caregiver use.


Assuntos
Consumo de Bebidas Alcoólicas , Cuidadores , Comportamento Infantil , Comportamento Problema , Humanos , Criança , Masculino , Feminino , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , África do Sul/epidemiologia , Alcoolismo/epidemiologia , Estudos Transversais
11.
Diabet Med ; 39(10): e14911, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35789029

RESUMO

INTRODUCTION: The effects of the COVID-19 pandemic on mental health have been profound. Mental health and diabetes self-care are inter-related. We examined whether COVID-19 anxiety, depressive symptoms and health anxiety were associated with domains of diabetes self-management and investigated whether greater COVID-19 anxiety syndrome would independently contribute to suboptimal diabetes self-care. RESEARCH DESIGN AND METHODS: Surveys were sent to people attending diabetes clinics of three London hospitals. Participants completed the Diabetes Self-Management Questionnaire (DSMQ), the COVID-19 Anxiety Syndrome Scale (C-19 ASS), which measures perseveration and avoidant maladaptive coping behaviour, assessed with measures of co-existent depressive symptoms and anxiety, controlling for age, gender and social deprivation. Clinical data, including pre- and post-lockdown HbA1c measures, were obtained from hospital records for 369 respondents, a response rate of 12.8%. RESULTS: Depressive symptom scores were high. Both pre-existing health anxiety and depressive symptoms were independently linked to improvable measures of diabetes care, as was lower socio-economic rank. However, avoidant COVID-19 anxiety responses were independently associated with higher diabetes self-care scores. HbA1c levels improved modestly over the year of UK lockdown in this cohort. CONCLUSION: During the height of lockdown, avoidant coping behaviours characteristic of the COVID-19 anxiety syndrome may in fact work to improve diabetes self-care, at least in the short term. We recommend screening for depressive symptoms and being aware of the significant minority of people with COVID-19 anxiety syndrome who may now find it difficult to re-engage with face-to-face clinic opportunities.


Assuntos
COVID-19 , Diabetes Mellitus , Autogestão , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Depressão/epidemiologia , Depressão/psicologia , Depressão/terapia , Humanos , Pandemias
12.
J Pediatr Gastroenterol Nutr ; 74(1): 104-109, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560722

RESUMO

OBJECTIVES: To systematically review the social outcomes of patients with biliary atresia (BA), including educational, employment and family outcomes. METHODS: We conducted a systematic review of Medline, EMBASE, Global Health, Maternity and Infant Care Database, supplemented by reference searching. National Heart, Lung and Blood Institute scoring was conducted for quality assessment. The PROSPERO registration ID was CRD42020178846. RESULTS: Fifty-one studies were included (41 cohort, 10 cross-sectional), including 4631 participants across 16 countries. Cohorts were BA post-liver transplant (LT) (18 studies), native liver survivors (NLS) (16 studies), mixed (13 studies) and four other cohorts. Outcomes covered; education (n = 35), employment (n = 16), family outcomes (n = 22), and social functioning (n = 22). BA patients had lower school functioning scores than controls, with no difference between NLS versus post-LT. Between 2% and 48% of children required additional educational support. Between 60% and 100% of adult patients with BA were employed. Pregnancies were described in 17 studies, with small samples, and some noted complications. Social functioning scores were similar to healthy controls in 8 of 11 comparisons. CONCLUSIONS: Despite BA being the primary indication for liver transplantation in childhood, social outcomes for children and adolescents are predominantly reported in non-controlled, single-centre survey-based studies. School functioning is lower compared to peer groups, with no evidence of a difference for those having a liver transplant. We recommend routine psychosocial assessment of these patients during follow-up, alongside multi-centre collaborations, to maximise the quality of evidence for future patients.


Assuntos
Atresia Biliar , Transplante de Fígado , Adolescente , Adulto , Atresia Biliar/psicologia , Atresia Biliar/cirurgia , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Gravidez , Sobreviventes/psicologia
13.
Pediatr Nephrol ; 37(8): 1775-1788, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34647173

RESUMO

Paediatric acute liver failure (PALF) is a rare but devastating condition with high mortality. An exaggerated inflammatory response is now recognised as pivotal in the pathogenesis and prognosis of ALF, with cytokine spill from the liver to systemic circulation implicated in development of multi-organ failure associated with ALF. With advances in medical management, especially critical care, there is an increasing trend towards spontaneous liver regeneration, averting the need for emergency liver transplantation or providing stability to the patient awaiting a graft. Hence, research is ongoing for therapies, including extracorporeal liver support devices, that can bridge patients to transplant or spontaneous liver recovery. Considering the immune-related pathogenesis and inflammatory phenotype of ALF, plasma exchange serves as an ideal liver assist device as it performs both the excretory and synthetic functions of the liver and, in addition, works as an immunomodulatory therapy by suppressing the early innate immune response in ALF. After a recent randomised controlled trial in adults demonstrated a beneficial effect of high-volume plasma exchange on clinical outcomes, this therapy was incorporated in European Association for the Study of Liver (EASL) recommendations for managing adult patients with ALF, but no guidelines exist for PALF. In this review, we discuss rationale, timing, practicalities, and existing evidence regarding the use of plasma exchange as an immunomodulatory treatment in PALF. We discuss controversies in delivery of this therapy as an extracorporeal device, and practicalities of use of plasma exchange as a 'hybrid' therapy alongside other extracorporeal liver assist devices, before finally reviewing outstanding research questions for the future.


Assuntos
Falência Hepática Aguda , Transplante de Fígado , Criança , Cuidados Críticos , Humanos , Falência Hepática Aguda/terapia , Insuficiência de Múltiplos Órgãos , Troca Plasmática
14.
Proc Natl Acad Sci U S A ; 116(46): 22959-22965, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31659026

RESUMO

Jumping spiders (Salticidae) rely on accurate depth perception for predation and navigation. They accomplish depth perception, despite their tiny brains, by using specialized optics. Each principal eye includes a multitiered retina that simultaneously receives multiple images with different amounts of defocus, and from these images, distance is decoded with relatively little computation. We introduce a compact depth sensor that is inspired by the jumping spider. It combines metalens optics, which modifies the phase of incident light at a subwavelength scale, with efficient computations to measure depth from image defocus. Instead of using a multitiered retina to transduce multiple simultaneous images, the sensor uses a metalens to split the light that passes through an aperture and concurrently form 2 differently defocused images at distinct regions of a single planar photosensor. We demonstrate a system that deploys a 3-mm-diameter metalens to measure depth over a 10-cm distance range, using fewer than 700 floating point operations per output pixel. Compared with previous passive depth sensors, our metalens depth sensor is compact, single-shot, and requires a small amount of computation. This integration of nanophotonics and efficient computation brings artificial depth sensing closer to being feasible on millimeter-scale, microwatts platforms such as microrobots and microsensor networks.


Assuntos
Cristalino/química , Óptica e Fotônica/instrumentação , Aranhas/fisiologia , Animais , Percepção de Profundidade , Desenho de Equipamento , Olho/química , Metais/química , Visão Ocular
15.
J Pediatr Gastroenterol Nutr ; 72(2): 184-193, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427793

RESUMO

ABSTRACT: Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?


Assuntos
Atresia Biliar , Microbioma Gastrointestinal , Adulto , Atresia Biliar/etiologia , Criança , Disbiose , Transplante de Microbiota Fecal , Humanos , Lactente , Fatores de Risco
16.
J Pediatr Gastroenterol Nutr ; 73(1): 93-98, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33720092

RESUMO

OBJECTIVES: To assess the utility of prognostic scoring systems for adolescents with biliary atresia (BA) surviving with native liver, for predicting the subsequent requirement for liver transplantation (LT). METHODS: Single-centre retrospective analysis of 397 BA patients who received Kasai Portoenterostomy (KP) 1980-1996 and survived with the native liver at 16 years. Laboratory and clinical variables at 16 years (timepoint 16 years) were used to calculate (i) LT allocation scores; Model for End-Stage Liver Disease [MELD/MELD-sodium (Na)], and UK End-Stage Liver Disease (UKELD); (ii) Mayo Primary Sclerosing Cholangitis risk score (MayoPSC) and (iii) a modified Paediatric End-Stage Liver Disease (PELD) score. Scores were compared between patients requiring LT after 16 years of age (LT > 16 years), and those who survived with native liver, at the latest follow-up. Additional subgroup analysis for patients with data available at 12 years (timepoint 12 years). RESULTS: MELD (area under the receiver operating characteristic [AUROC] 0.847) and UKELD (AUROC: 0.815) at 16 years of age predict the need for LT > 16 years. No advantage for MELD-Na over MELD was demonstrated. MELD >8.5 and UKELD >47 predicted LT > 16 years with 84% and 79% sensitivity and 73% and 73% specificity. PELD had a similar performance to MELD, but superiority to UKELD. MayoPSC revealed predictive accuracy for LT >16 years (AUROC 0.859), with a score of >0.87 predicting LT > 16 years with 85% sensitivity and 82% specificity. At timepoint 12 years, MELD and MayoPSC predicted LT >16 years. Change in MELD, PELD and MayoPSC between 12 and 16 years of age, was associated with LT >16 years. CONCLUSIONS: Adult LT allocation scores may help monitor progress in adolescent BA, but the omission of relevant risk factors limits their utility for listing in this cohort. A BA-specific prognostic score would improve the management of adolescent BA.


Assuntos
Atresia Biliar , Doença Hepática Terminal , Adolescente , Adulto , Atresia Biliar/diagnóstico , Atresia Biliar/cirurgia , Criança , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
J Asthma ; 58(1): 112-120, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532264

RESUMO

OBJECTIVE: Asthma outcomes are significantly worse for minority groups, including South Asians (SAs), in high-income settings. Despite this, comparatively few existing studies have focused on SAs when studying the effectiveness of behavioral interventions on asthma self-management, and no prior study has synthesized these findings. We review the effectiveness of behavioral interventions on asthma management in adults and children of SA origin across low- (LICs), middle- (MICs), and high-income countries (HICs). METHODS: Data sources included EMBASE, MEDLINE, Cochrane Library and Trial registries: WHO, ICTRP and ClinicalTrials.gov. Eligibility criteria: randomized controlled trials (RCTs), quasi-RCTs and non-RCTs (controlled before-after [CBA] studies), published in English, with no publication year or country restrictions in adults and children of South Asian origin. Exclusion criteria: those focusing solely on pharmacological interventions. Search terms were "asthma" and "South Asian". RESULTS: We included 33 studies, 27 from MICs and 6 from HICs (education [n = 10], self-management plans [n = 6], yoga/breathing exercises [n = 10]) organizational interventions [n =1], diet therapy [n = 1] and combined interventions [n = 5]). Outcome measures included: blood biochemistry, lung function, healthcare utilization and quality of life. A meta-analysis was not performed due to significant study heterogeneity. CONCLUSION: Behavioral interventions for asthma management in SAs are effective. Educational interventions that aim to optimize asthma knowledge, control, and inhaler technique, and yoga/breathing exercises are most effective for improved long-term outcomes in adults and children across LICs and MICs. Further research is needed to evaluate the effectiveness of all behavioral interventions for SAs in HICs to better inform current guidance by policy makers and health care providers.


Assuntos
Asma/terapia , Terapia Comportamental , Autogestão , Adulto , Ásia , Criança , Humanos
18.
Public Health Nutr ; 24(11): 3498-3519, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33593453

RESUMO

OBJECTIVE: To systematically review the literature with the primary aim of identifying behavioural interventions to improve vitamin D stores in children from at-risk ethnic groups. DESIGN: Review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PROSPERO registration number: CRD42017080932. Health Behaviour Model and Behaviour Change Wheel framework constructs used to underpin evaluation of interventions. Methodological quality evaluated using Cochrane Risk of Bias, Cochrane ROBINS-I and NHLBI tools. SETTING: Databases Cochrane Library, MEDLINE, EMBASE, CINAHL with secondary search of Google Scholar. No country limits set. Papers between January 1990 and February 2018, published in English included. Anticipating study heterogeneity, outcome measures not pre-specified and identified from individual full papers. Updated literature search November 2020. PARTICIPANTS: Patient or population including pregnant women, newborns and children aged under 18 years, from Asian or African ethnic groups. RESULTS: Of 10 690 articles screened, 298 underwent full-text review, with 24 ultimately included for data extraction. All identified studies conducted a vitamin D pharmacological supplementation intervention, with two also incorporating a behavioural intervention strategy. No study explicitly defined a primary aim of evaluating a behavioural intervention, undertaken to study its effect on vitamin D supplement uptake. CONCLUSIONS: There is a need to address the paucity of data in ethnic at-risk children on how behavioural interventions ideally developed and co-produced with the community under study, affect and help improve vitamin D uptake, within the antenatal and pregnancy phase as well as during childhood.


Assuntos
Etnicidade , Vitamina D , Adolescente , Terapia Comportamental , Criança , Pré-Escolar , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Recém-Nascido , Gravidez , Vitaminas
19.
Health Expect ; 24(4): 1270-1285, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33932315

RESUMO

BACKGROUND: Our study aimed to evaluate to what extent Zero2 Expo's 'Birthing a Better Future', a co-created multimedia exhibition, was effective in raising awareness on the importance of the first 1001 days of life and explore what refinements would help to optimize the impact of future exhibitions. METHODS: We conducted a mixed-methods evaluation of the exhibition delivered in the John Radcliffe Hospital, Oxford. Through convenience sampling, 14 participants were selected to participate in 12 structured interviews and 19 participants completed a questionnaire. Interviews were thematically analysed alongside quantitative analysis of questionnaire responses through Likert scales. RESULTS: The majority (78.6%, n = 11/14) of participants who completed the questionnaire either agreed or strongly agreed that the exhibition raised their awareness about the first 1001 days of life. This was supported by the analysis of interviews. The use of art was found to provoke an emotional engagement from participants. Participants felt that the length of the written pieces and location of the exhibition were important factors for designers to consider in future exhibitions. CONCLUSION: This study demonstrated that multimedia exhibitions, combining science with art, may be an effective way to raise awareness of public health messages. Engaging with key stakeholders will be an essential step in order to improve future public health exhibitions. PUBLIC CONTRIBUTION: When designing the study, the public reviewed the study tools, which were refined based on their feedback. At every phase of the study, members of the public who are artists co-created the exhibition content.


Assuntos
Proteção da Criança , Conscientização , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Inquéritos e Questionários
20.
Child Psychiatry Hum Dev ; 52(6): 1194-1217, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33369706

RESUMO

Childhood exposure to alcohol misuse by household adults has been related to childhood developmental delay, cognitive impacts, mental illness, and problem behaviours. Most evidence comes from high income countries. This systematic review only included studies from low- and middle-income countries (LMICs). Five databases were searched from 1990-2020. Twenty-eight studies of children 0-12 years were included, with 42,599 participants from 11 LMICs. The most common outcome was behavioural problems/disorders (19 studies). Despite varying study designs, this review found that alcohol misuse by household members in LMICs is associated with adverse child neurodevelopmental outcomes, although casual inferences cannot be drawn in the absence of well conducted prospective studies. Statistically significant correlations were described between parental alcohol misuse and child emotional and behavioural difficulties, cognitive delay, and risky behaviours. In future, prospective cohort studies are recommended, with adjustment for confounders.


Assuntos
Países em Desenvolvimento , Transtornos Mentais , Adulto , Criança , Características da Família , Humanos , Renda , Estudos Prospectivos
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