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1.
Rev Sci Instrum ; 94(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117203

RESUMO

We present the development of a flexible tape-drive target system to generate and control secondary high-intensity laser-plasma sources. Its adjustable design permits the generation of relativistic MeV particles and x rays at high-intensity (i.e., ≥1 × 1018 W cm-2) laser facilities, at high repetition rates (>1 Hz). The compact and robust structure shows good mechanical stability and a high target placement accuracy (<4 µm RMS). Its compact and flexible design allows for mounting in both the horizontal and vertical planes, which makes it practical for use in cluttered laser-plasma experimental setups. The design permits ∼170° of access on the laser-driver side and 120° of diagnostic access at the rear. A range of adapted apertures have been designed and tested to be easily implemented to the targetry system. The design and performance testing of the tape-drive system in the context of two experiments performed at the COMET laser facility at the Lawrence Livermore National Laboratory and at the Advanced Lasers and Extreme Photonics (ALEPH) facility at Colorado State University are discussed. Experimental data showing that the designed prototype is also able to both generate and focus high-intensity laser-driven protons at high repetition rates are also presented.

2.
Water Res X ; 19: 100183, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37292177

RESUMO

This paper reports conclusions from a recent study completed for the Water Research Foundation and the State of California to offer guidance on UV-chlorine advanced oxidation for potable water reuse. The fundamentals of UV-chlorine advanced oxidation are discussed, and lessons learned from some of the early adopters of this technology are presented. Important highlights include the significant impact of ammonia and chloramines on UV-chlorine treatment, challenges associated with predicting UV-chlorine performance due to complex photochemistry, and an ongoing need to monitor potential byproducts and transformation products when employing any form of advanced oxidation for potable reuse.

3.
Biochim Biophys Acta Mol Cell Res ; 1870(6): 119479, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37100352

RESUMO

BACKGROUND: The large extracellular matrix protein SVEP1 mediates cell adhesion via integrin α9ß1. Recent studies have identified an association between a missense variant in SVEP1 and increased risk of coronary artery disease (CAD) in humans and in mice Svep1 deficiency alters the development of atherosclerotic plaques. However how SVEP1 functionally contributes to CAD pathogenesis is not fully understood. Monocyte recruitment and differentiation to macrophages is a key step in the development of atherosclerosis. Here, we investigated the requirement for SVEP1 in this process. METHODS: SVEP1 expression was measured during monocyte-macrophage differentiation in primary monocytes and THP-1 human monocytic cells. SVEP1 knockout THP-1 cell lines and the dual integrin α4ß1/α9ß1 inhibitor, BOP, were utilised to investigate the effect of these proteins in THP-1 cell adhesion, migration and cell spreading assays. Subsequent activation of downstream integrin signalling intermediaries was quantified by western blotting. RESULTS: SVEP1 gene expression increases in monocyte to macrophage differentiation in human primary monocytes and THP-1 cells. Using two SVEP1 knockout THP-1 cells we observed reduction in monocyte adhesion, migration, and cell spreading compared to control cells. Similar results were found with integrin α4ß1/α9ß1 inhibition. We demonstrate reduced activity of Rho and Rac1 in SVEP1 knockout THP-1 cells. CONCLUSIONS: SVEP1 regulates monocyte recruitment and differentiation phenotypes through an integrin α4ß1/α9ß1 dependent mechanism. GENERAL SIGNIFICANCE: These results describe a novel role for SVEP1 in monocyte behaviour relevant to CAD pathophysiology.


Assuntos
Integrina alfa4beta1 , Monócitos , Humanos , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular/genética , Integrina alfa4beta1/metabolismo , Macrófagos/metabolismo
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-968514

RESUMO

Purpose@#Children with inflammatory bowel disease (IBD) frequently undergo clinical assessments, involving triadic communication between clinician, parent, and child. During such encounters parents are traditionally the main communicator of information on their child’s IBD, including subjective symptom reports. The level of agreement between children and their parents for IBD symptoms is poorly understood, and this study aimed to examine this factor. @*Methods@#This was a cross-sectional study among children with IBD, and one parent. A validated paediatric IBD symptom report tool (IBDnow) enabled children and their parent to rate seven pain, well-being, and stool metrics, with dyads completing the tool concurrently. @*Results@#were assessed using: Individual agreement: proportion of identical symptom reports by each dyad (ideal score >0.7); Category agreement: percentage of identical reports for IBDnow metrics for the cohort; Inter-rater reliability: Gwet’s AC1 coefficient with higher scores indicating better reliability (maximum=1). @*Results@#Seventy-four parent/child dyads participated; child’s mean age 12.2 years (standard deviation [SD] 2.9, range 6-16), mean time since diagnosis 2.8 years (SD 3), 54% female, 73% had Crohn’s Disease. Mean individual agreement level was 0.6, with 27% of dyads agreeing on ≥6/7 IBDnow metrics. Category agreement was reported by 61% of dyads, 20% of parents overestimated, and 19% underestimated, their child’s symptoms. Inter-rater reliability ranged from fair to good. @*Conclusion@#These results should improve clinician awareness of how IBD symptom reports from parents may introduce bias. Children should be considered the most important source of symptom reports, and tools such as IBDnow utilised to enhance communication.

5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-968507

RESUMO

Purpose@#The cow’s milk-related-symptom-score (CoMiSS) tool was developed as an awareness tool for the assessment of cow’s milk-related symptoms in infants or children.Fecal calprotectin (FC) is a noninvasive biomarker of gut inflammation that can be measured in serum and stool. This study aimed to investigate the relationship between FC levels and CoMiSS scores in infants with cow’s milk protein allergy. @*Methods@#Infants (aged 6–12 months) who were allergic to cow’s milk protein were enrolled prospectively. Following completion of the CoMiSS scoring, the infants were divided into group 1 (positive CoMiSS scores ≥12) and group 2 (negative CoMiSS scores <12). FC was measured using immunoassay. @*Results@#Of the 120 infants enrolled in this study, 60 (50.0%) had positive CoMiSS scores (group 1), while 60 (50.0%) had negative scores (group 2). The mean FC level was higher in the infants in group 1 than those in group 2 (2,934.57 µg/g vs. 955.13 µg/g; p<0.001). In addition, there was a positive correlation between FC and CoMiSS scores (R=0.168, p<0.0001). A FC level of 1,700 µg/g provided a sensitivity of 98.3%, specificity of 93.3%, and accuracy of 95.8% for the diagnosis of cow’s milk protein allergy (CMPA). @*Conclusion@#FC measurement may have a role in the assessing infants with CMPA.

6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-967666

RESUMO

Objectives@#Pregnancy complications, including pre-eclampsia, gestational diabetes (GDM), and perinatal mood and anxiety disorders (PMADs), impact long-term health. We compared the frequency of screening documentation for pregnancy complications versus a general medical history at well woman visits between providers in primary care and obstetrics and gynecology. @*Methods@#We conducted a retrospective cohort study of subjects with at least 1 prior birth who presented for a well woman visit in 2019-2020. Charts were reviewed for documentation of a general medical history (hypertension, diabetes, and mood disorders) versus screening for comparable obstetric complications (pre-eclampsia, GDM, and PMADs). The results were compared using the McNemar and chi-square tests as appropriate. @*Results@#In total, 472 encounters were identified, and 137 met the inclusion criteria. Across specialties, clinicians were significantly more likely to document general medical conditions than pregnancy complications, including hypertensive disorders (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.18 to 5.48), diabetes (OR, 7.67; 95% CI, 3.27 to 22.0), and mood disorders (OR, 10.5; 95% CI, 3.81 to 40.3). Obstetrics and gynecology providers were more likely to document any pregnancy history (OR, 4.50; 95% CI, 1.24 to 16.27); however, they were not significantly more likely to screen for relevant obstetric complications (OR, 2.49; 95% CI, 0.90 to 6.89). Overall, the rate of pregnancy complication documentation was low in primary care and obstetrics and gynecology clinics (8.8 and 19.0%, respectively). @*Conclusions@#Obstetrics and gynecology providers more frequently documented a pregnancy history than those in primary care; however, the rate was low across specialties, and providers reported screening for clinically relevant complications less frequently than for general medical conditions.

7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-977316

RESUMO

Crohn’s disease (CD) is a chronic, incurable and relapsing disease involving any part of the gastrointestinal tract and exclusive enteral nutrition (EEN) is first-line therapy. Few studies have examined the patient experience of EEN. The aim of this study was to assess the child’ s experiences of EEN, to identify problematic themes and understand the child’s mindset. Children with CD who previously completed EEN were recruited to complete a survey. All data were analyzed using Microsoft Excel and reported as N (%). Forty-four children (mean age 11.3 years) consented to participate. Sixty-eight percent of children reported limited formula flavors as the most challenging aspect and 68% of children identified ‘support’ to be important. This study highlights the psychological impact of chronic disease and its therapies on children. Providing adequate support is essential to insure EEN is successful. Further studies are required to determine psychological support strategies for children taking EEN.

8.
Small GTPases ; 13(1): 307-326, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342857

RESUMO

P-Rex1 and P-Rex2 are guanine-nucleotide exchange factors (GEFs) that activate Rac small GTPases in response to the stimulation of G protein-coupled receptors and phosphoinositide 3-kinase. P-Rex Rac-GEFs regulate the morphology, adhesion and migration of various cell types, as well as reactive oxygen species production and cell cycle progression. P-Rex Rac-GEFs also have pathogenic roles in the initiation, progression or metastasis of several types of cancer. With one exception, all P-Rex functions are known or assumed to be mediated through their catalytic Rac-GEF activity. Thus, inhibitors of P-Rex Rac-GEF activity would be valuable research tools. We have generated a panel of small-molecule P-Rex inhibitors that target the interface between the catalytic DH domain of P-Rex Rac-GEFs and Rac. Our best-characterized compound, P-Rex inhibitor 1 (PREX-in1), blocks the Rac-GEF activity of full-length P-Rex1 and P-Rex2, and of their isolated catalytic domains, in vitro at low-micromolar concentration, without affecting the activities of several other Rho-GEFs. PREX-in1 blocks the P-Rex1 dependent spreading of PDGF-stimulated endothelial cells and the production of reactive oxygen species in fMLP-stimulated mouse neutrophils. Structure-function analysis revealed critical structural elements of PREX-in1, allowing us to develop derivatives with increased efficacy, the best with an IC50 of 2 µM. In summary, we have developed PREX-in1 and derivative small-molecule compounds that will be useful laboratory research tools for the study of P-Rex function. These compounds may also be a good starting point for the future development of more sophisticated drug-like inhibitors aimed at targeting P-Rex Rac-GEFs in cancer.


Assuntos
Fatores de Troca do Nucleotídeo Guanina , Neoplasias , Animais , Camundongos , Células Endoteliais/metabolismo , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fosfatidilinositol 3-Quinases , Espécies Reativas de Oxigênio
9.
AJNR Am J Neuroradiol ; 43(7): 1048-1053, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35772801

RESUMO

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.


Assuntos
Neoplasias Encefálicas , Histonas , Malformações do Desenvolvimento Cortical , Transtornos do Neurodesenvolvimento , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Células Germinativas/patologia , Histonas/genética , Humanos , Masculino , Malformações do Desenvolvimento Cortical/patologia , Transtornos do Neurodesenvolvimento/patologia , Estudos Retrospectivos
10.
Surg Endosc ; 36(2): 1206-1214, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33661381

RESUMO

INTRODUCTION: Cholecystectomy is the accepted treatment for patients with symptomatic gallstones. In this study, we evaluate a simplified strategy for managing suspected synchronous choledocholithiasis by focussing on intra-operative imaging as the primary decision-making tool to target common bile duct (CBD) stone treatment. METHODS: All elective and emergency patients undergoing laparoscopic cholecystectomy (LC) for gallstones with any markers of synchronous choledocholithiasis were included. Patients unfit for surgery or who had pre-operative proof of choledocholithiasis were excluded. Intra-operative imaging was used for evaluation of the CBD. CBD stone treatment was with bile duct exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (LC + ERCP). Outcomes were safety, effectiveness and efficiency. RESULTS: 506 patients were included. 371 (73%) had laparoscopic ultrasound (LUS), 80 (16%) had on-table cholangiography (OTC) and 55 (11%) had both. 164 (32.4%) were found to have CBD stones. There was no increase in length of surgery for LC + LUS compared with average time for LC only in our unit (p = 0.17). 332 patients (65.6%) had clear ducts. Imaging was indeterminate in 10 (2%) patients. Overall morbidity was 10.5%. There was no mortality. 142 (86.6%) patients with stones on intra-operative imaging proceeded to LCBDE. 22 (13.4%) patients had ERCP. Sensitivity and specificity of intra-operative imaging were 93.3 and 99.1%, respectively. Success rate of LCBDE was 95.8%. Effectiveness was 97.8%. CONCLUSIONS: Eliminating pre-operative bile duct imaging in favour of intra-operative imaging is safe and effective. When combined with intra-operative stone treatment, this method becomes a true 'single-stage' approach to managing suspected choledocholithiasis.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase , Cálculos Biliares , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia por Ressonância Magnética , Colecistectomia Laparoscópica/métodos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Humanos
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-918696

RESUMO

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current metaanalysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as “cystic fibrosis,” “intestine,” “calprotectin,” and “inflammation.” Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/ dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I2 =0), pulmonary function (r=–0.39; 95% CI, –0.58 to –0.15; p=0.002; I2 =60%), body mass index (r=–0.514; 95% CI, 0.26 to 0.69; p2 =71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

12.
Semin Fetal Neonatal Med ; 26(5): 101272, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34417137

RESUMO

Neonatal encephalopathy (NE) describes the clinical syndrome of a newborn with abnormal brain function that may result from a variety of etiologies. HIE should be distinguished from neonatal encephalopathy due to other causes using data gathered from the history, physical and neurological exam, and further investigations. Identifying the underlying cause of encephalopathy has important treatment implications. This review outlines conditions that cause NE and may be mistaken for HIE, along with their distinguishing clinical features, pathophysiology, investigations, and treatments. NE due to brain malformations, vascular causes, neuromuscular causes, genetic conditions, neurogenetic disorders and inborn errors of metabolism, central nervous system (CNS) and systemic infections, and toxic/metabolic disturbances are discussed.


Assuntos
Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Humanos , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/terapia
13.
Phys Rev E ; 103(3-1): 033203, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33862755

RESUMO

The generation of hot, directional electrons via laser-driven stimulated Raman scattering (SRS) is a topic of great importance in inertial confinement fusion (ICF) schemes. Little recent research has been dedicated to this process at high laser intensity, in which back, side, and forward scatter simultaneously occur in high energy density plasmas, of relevance to, for example, shock ignition ICF. We present an experimental and particle-in-cell (PIC) investigation of hot electron production from SRS in the forward and near-forward directions from a single speckle laser of wavelength λ_{0}=1.053µm, peak laser intensities in the range I_{0}=0.2-1.0×10^{17}Wcm^{-2} and target electron densities between n_{e}=0.3-1.6%n_{c}, where n_{c} is the plasma critical density. As the intensity and density are increased, the hot electron spectrum changes from a sharp cutoff to an extended spectrum with a slope temperature T=34±1keV and maximum measured energy of 350 keV experimentally. Multidimensional PIC simulations indicate that the high energy electrons are primarily generated from SRS-driven electron plasma wave phase fronts with k vectors angled ∼50^{∘} with respect to the laser axis. These results are consistent with analytical arguments that the spatial gain is maximized at an angle which balances the tendency for the growth rate to be larger for larger scattered light wave angles until the kinetic damping of the plasma wave becomes important. The efficiency of generated high energy electrons drops significantly with a reduction in either laser intensity or target electron density, which is a result of the rapid drop in growth rate of Raman scattering at angles in the forward direction.

15.
Patient Educ Couns ; 104(11): 2834-2838, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33838939

RESUMO

OBJECTIVES: To explore gender-based differences in experiences with a telehealth-delivered intervention for reduction of cardiovascular risk. METHODS: We conducted 23 semi-structured qualitative interviews by telephone with 11 women and 12 men who received a 12-month, pharmacist-delivered, telephone-based medication and behavioral management intervention. We used content analysis to identify themes. RESULTS: We identified three common themes for both men and women: ease and convenience of phone support, preference for proactive outreach, and need for trust building in the context of telehealth. While both genders appreciated the social support from the intervention pharmacist, women voiced appreciation for accountability whereas men generally spoke about encouragement. CONCLUSIONS: Rapport building may differ between telehealth and in-person healthcare visits; our work highlights how men and women's experiences can differ with telehealth care and which can inform the development of future, purposeful rapport building activities to strengthen the clinician-patient interaction. PRACTICE IMPLICATIONS: Clinicians should seek opportunities to provide frequent and routine support for patients with chronic disease. Telehealth interventions may benefit from gender-specific tailoring of social support.


Assuntos
Doenças Cardiovasculares , Telemedicina , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Masculino , Avaliação de Resultados da Assistência ao Paciente , Pesquisa Qualitativa , Fatores de Risco , Telefone
16.
PLoS One ; 16(3): e0247972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33684160

RESUMO

INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786.


Assuntos
Injúria Renal Aguda , Anticorpos Monoclonais Humanizados , Função Retardada do Enxerto , Interleucina-18/sangue , Transplante de Rim , Doadores de Tecidos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
17.
Psychol Med ; 51(8): 1338-1344, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32063235

RESUMO

BACKGROUND: Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. METHODS: A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. RESULTS: In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. CONCLUSIONS: Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.


Assuntos
Apatia , Disfunção Cognitiva , Doença de Huntington , Humanos , Pré-Escolar , Doença de Huntington/genética , Doença de Huntington/psicologia , Estudos Prospectivos , Disfunção Cognitiva/complicações , Cognição
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-904058

RESUMO

BACKGROUND@#Atelocollagen is widely recognized as a biomaterial for regenerative medicine because of its good compatibility and low antigenicity. Injury of the outermost layer of articular cartilage, known as the lamina splendens, can lead to osteoarthritis (OA) and eventually full-thickness cartilage loss. The intra-articular injection of atelocollagen has been designed to restore the cartilage layer and cartilage defects in OA joints. In this study, we investigated the efficacy of atelocollagen as a cartilage supplement for joint defects. @*METHODS@#In this study, we evaluated the therapeutic effects of atelocollagen in animals with cartilage defects. Femoral groove defects were artificially created in 12 male New Zealand white rabbits, which were treated with intra-articular injection of either atelocollagen (experimental) or normal saline (control). The results were observed 3, 6, 9, and 12 weeks following macroscopic and histological evaluations. @*RESULTS@#At 3 weeks, cartilage tissue was restored in the experimental group, whereas the control group did not show signs of restoration. At 12 weeks, defects in both groups were filled with regenerated tissue, but the experimental group displayed a morphologically better appearance. Histologically, the regenerated tissue in the experimental group showed statistically significant improvement compared to the control group, with a structure similar to that of normal articular cartilage. @*CONCLUSION@#The results showed that the intra-articular injection of atelocollagen enhanced cartilage regeneration following rabbit patellar groove defects. Therefore, intra-articular injection of atelocollagen can be used as an effective supplement for joint defects.

19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-896354

RESUMO

BACKGROUND@#Atelocollagen is widely recognized as a biomaterial for regenerative medicine because of its good compatibility and low antigenicity. Injury of the outermost layer of articular cartilage, known as the lamina splendens, can lead to osteoarthritis (OA) and eventually full-thickness cartilage loss. The intra-articular injection of atelocollagen has been designed to restore the cartilage layer and cartilage defects in OA joints. In this study, we investigated the efficacy of atelocollagen as a cartilage supplement for joint defects. @*METHODS@#In this study, we evaluated the therapeutic effects of atelocollagen in animals with cartilage defects. Femoral groove defects were artificially created in 12 male New Zealand white rabbits, which were treated with intra-articular injection of either atelocollagen (experimental) or normal saline (control). The results were observed 3, 6, 9, and 12 weeks following macroscopic and histological evaluations. @*RESULTS@#At 3 weeks, cartilage tissue was restored in the experimental group, whereas the control group did not show signs of restoration. At 12 weeks, defects in both groups were filled with regenerated tissue, but the experimental group displayed a morphologically better appearance. Histologically, the regenerated tissue in the experimental group showed statistically significant improvement compared to the control group, with a structure similar to that of normal articular cartilage. @*CONCLUSION@#The results showed that the intra-articular injection of atelocollagen enhanced cartilage regeneration following rabbit patellar groove defects. Therefore, intra-articular injection of atelocollagen can be used as an effective supplement for joint defects.

20.
Gut and Liver ; : 128-134, 2021.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-874571

RESUMO

Background/Aims@#This study assessed the significance of biliary stricture in symptomatic chronic pancreatitis patients requiring extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) to remove obstructing pancreatic calculi. @*Methods@#A total of 97 patients underwent ESWL followed by ERCP to remove pancreatic calculi between October 2014 and October 2017 at Virginia Mason Medical Center. Significant biliary stricture (SBS) was defined as a stricture with upstream dilation on computed tomography scan or magnetic resonance cholangiopancreatography scans accompanied by cholestasis and/or cholangitis. SBS was initially managed by either a plastic stent or fully covered self-expandable metallic stent (fcSEMS). If the stricture did not resolve, the stent was replaced with either multiple plastic stents or another fcSEMS. Data were collected by retrospectively reviewing the medical records. @*Results@#Biliary strictures were noted in approximately one-third of patients (34/97, 35%) undergoing ESWL for pancreatic calculi. Approximately one-third of the biliary strictures (11/34, 32%) were SBS. Pseudocysts were more frequently found in those with SBS (36% vs 8%, p=0.02), and all pseudocysts in the SBS group were located in the pancreatic head. The initial stricture resolution rates with fcSEMSs and plastic prostheses were 75% and 29%, respectively. The overall success rate for stricture resolution was 73% (8/11), and the recurrence rate after initial stricture resolution was 25% (2/8). @*Conclusions@#Although periductal fibrosis is the main mechanism underlying biliary stricture development in chronic pancreatitis, inflammation induced by obstructing pancreatic calculi, including pseudocysts, is an important contributing factor to SBS formation during the acute phase.

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