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1.
Ir J Psychol Med ; : 1-6, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738538

ABSTRACT

BACKGROUND: A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the 'Maskey report' (MR), highlighted substandard prescribing practices. The aim of this 'Maskey Impact Study' (MIS) was to explore changes to child and adolescent psychiatrists' prescribing practices following the MR. METHOD: The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160). RESULTS: 102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced 'meaningless' bureaucracy and medication mistrust among families. DISCUSSION: Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.

2.
Sci Rep ; 14(1): 605, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38182609

ABSTRACT

Laser plasma-based accelerators provide an excellent source of collimated, bright, and adequately coherent betatron-type x-ray pulses with potential applications in science and industry. So far the laser plasma-based betatron radiation has been described within the concept of classical Liénard-Wiechert potentials incorporated in particle-in-cell simulations, a computing power-demanding approach, especially for the case of multi-petawatt lasers. In this work, we describe the laser plasma-based generation of betatron radiation at the most fundamental level of quantum mechanics. In our approach, photon emission from the relativistic electrons in the plasma bubble is described within a nonlinear quantum electrodynamics (QED) framework. The reported QED-based betatron radiation results are in excellent agreement with similar results using Liénard-Wiechert potentials, as well as in very good agreement with betatron radiation measurements, obtained with multi-10-TW lasers interacting with He and multielectron N[Formula: see text] gas targets. Furthermore, our QED approach results in a dramatic reduction of the computational runtime demands, making it a favorable tool for designing betatron radiation experiments, especially in multi-petawatt laser facilities.

3.
Sci Rep ; 13(1): 20699, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38001241

ABSTRACT

Nanowire array targets exhibit high optical absorption when interacting with short, intense laser pulses. This leads to an increased yield in the production of accelerated particles for a variety of applications. However, these interactions are sensitive to the laser prepulse and could be significantly affected. Here, we show that an array of aligned nanowires is imploded when irradiated by an Amplified Spontaneous Emission pedestal of a [Formula: see text] laser with an intensity on the order of [Formula: see text]. Using radiation hydrodynamics simulations, we demonstrate that the electron density profile is radially compressed at the tip by the rocket-like propulsion of the ablated plasma. The mass density compression increases up to [Formula: see text] when a more dense nanowire array is used. This is due to the ablation pressure from the neighboring nanowires. These findings offer valuable information for selecting an appropriate target design for experiments aimed at enhancing production of accelerated particles.

4.
Phys Rev E ; 107(6-2): 065208, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37464686

ABSTRACT

We show that an ultra-high-pressure plasma can be generated when an aligned nanowire is irradiated by a laser with relativistic transparent intensity. Using a particle-in-cell simulation, we demonstrate that the expanded plasma following the z pinch becomes relativistically transparent and compressed longitudinally by the oscillating component of the ponderomotive force. The compressed structure persists throughout the pulse duration with a maximum pressure of 40Tbar when irradiated with a laser at an intensity of 10^{23}Wcm^{-2}, 5× higher than the z-pinch pressure. These results suggest an alternative approach to extending the current attainable pressure in the laboratory.

5.
Sex Health ; 20(3): iii-v, 2023 07.
Article in English | MEDLINE | ID: mdl-37463116
8.
Ir Med J ; 116(10): 881, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38258909

Subject(s)
Dyspnea , Neck Pain , Humans
10.
Med J Malaysia ; 77(3): 347-356, 2022 05.
Article in English | MEDLINE | ID: mdl-35638492

ABSTRACT

INTRODUCTION: Organ donation (OD) rates in Malaysia have remained suboptimal for decades. Healthcare professionals (HCPs) working in critical care areas are responsible for diagnosing brain death (BD) and initiating the OD process. Impact of their knowledge and attitudes on willingness to offer the option of OD to families of potential donors is unknown. METHODS: Knowledge and attitudes about BD, OD, and organ transplantation (OT) of critical care HCPs in a Malaysian transplant centre were studied using a validated questionnaire. Responses were analysed using multivariable analysis with willingness to offer the option of OD to families of potential donors as dependent variable. RESULTS: Age (p = 0.04), profession (doctors > nurses, p < 0.001), religion (Buddhists > others, p = 0.013) [but not ethnicity], higher knowledge scores for Brain Death Test, Brain Death Knowledge, Organ Donation and Transplantation, and overall knowledge score (p < 0.001) were associated with greater odds of offering OD to families. Belief in the reliable diagnosis of BD, confidence in explaining BD, and belief that OD will not affect religious services were significantly associated with willingness to offer OD, while HCPs who were willing to personally donate organs had greatest odds (p < 0.001). Other factors that significantly influenced HCPs' willingness to offer included their perception about families' willingness to donate, body disfigurement, and confidence in OT. CONCLUSIONS: Overall, HCPs had highly positive attitudes. However, potential barriers in offering OD to families were identified. Proven interventions from international experience could help address these issues and likely improve OD rates in Malaysia.


Subject(s)
Organ Transplantation , Tissue and Organ Procurement , Brain Death/diagnosis , Critical Care , Health Knowledge, Attitudes, Practice , Humans , Surveys and Questionnaires , Tertiary Care Centers
11.
Med J Malaysia ; 77(2): 224-231, 2022 03.
Article in English | MEDLINE | ID: mdl-35338631

ABSTRACT

INTRODUCTION: In Malaysia, the prevalence of diabetes mellitus has been increasing annually, currently affecting 18.3% of the population. Diabetic foot ulcer, a common complication of diabetes, is associated with high morbidity and mortality, consequently increasing health care expenditure. A previous study showed that foot care knowledge and foot self-care practices help to reduce the development of ulcers.1,2 This study aims to identify the level of foot care knowledge and self-care practices among diabetic patients in the primary care setting. OBJECTIVE: This study was to determine the level of foot care knowledge and foot self-care practices among diabetic patients in the primary care setting in Penang Island and its determinants and the correlation between level of foot care knowledge and self-care practices among diabetic patients. MATERIAL AND METHODS: A cross sectional study was performed on 311 diabetic patients who were registered to two government health clinics in Penang. Information regarding respondents' demographic status, foot care knowledge, and foot self-care practices were gathered using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Sciences (SPSS) 22. The Mann-Whitney U test and Kruskal-Wallis test were applied to the analysis. Multiple linear regression was performed to identify the determinants. Correlation between knowledge and self-care practice was determined using the linear regression model. RESULTS: One hundred and sixty-five (53.1%) respondents achieved good knowledge scores and 196 respondents (63%) achieved good self-care practice scores. The median age of respondents was 61 years, who were mostly females (56.6%), Malays (41.2%), and unemployed (48.6%). Median HbA1c level was 7.5%, and 42.8% of respondents had diabetes for 5 to 10 years. Lowest scores for knowledge and self-care practices were observed in foot skin care questions. Formal foot care education was found to be a significant predictor of foot care knowledge (p<0.05, 95% CI -1.102, -0.098). Foot care knowledge was significantly and positively correlated with foot self-care practices (p<0.001, 95% CI 0.548, 0.727). CONCLUSION: Foot care knowledge has significant positive correlation with foot self-care practices. Empowering diabetic patients with foot care knowledge may lead to significantly better foot self-care practices.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Cross-Sectional Studies , Diabetic Foot/epidemiology , Diabetic Foot/therapy , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Primary Health Care , Self Care
12.
Curr HIV/AIDS Rep ; 19(2): 154-165, 2022 04.
Article in English | MEDLINE | ID: mdl-35147855

ABSTRACT

PURPOSE OF REVIEW: Effective ways to diagnose the remaining people living with HIV who do not know their status are a global priority. We reviewed the use of risk-based tools, a set of criteria to identify individuals who would not otherwise be tested (screen in) or excluded people from testing (screen out). RECENT FINDINGS: Recent studies suggest that there may be value in risk-based tools to improve testing efficiency (i.e. identifying those who need to be tested). However, there has not been any systematic reviews to synthesize these studies. We identified 18,238 citations, and 71 were included. The risk-based tools identified were most commonly from high-income (51%) and low HIV (<5%) prevalence countries (73%). The majority were for "screening in" (70%), with the highest performance tools related to identifying MSM with acute HIV. Screening in tools may be helpful in settings where it is not feasible or recommended to offer testing routinely. Caution is needed for screening out tools, where there is a trade-off between reducing costs of testing with missing cases of people living with HIV.


Subject(s)
HIV Infections , Delivery of Health Care , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Testing , Humans , Mass Screening , Prevalence
13.
Int J Comput Assist Radiol Surg ; 17(1): 55-64, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34533757

ABSTRACT

PURPOSE: Sliding genioplasty is used to surgically correct a retruded or misaligned chin: in this procedure, an osteotomy is performed and the bony segment is repositioned. In this study we investigate the effect of surgical parameters (bony segment movement, osteotomy design) on postop soft tissue changes in a patient cohort. METHODS: Seven patients were retrospectively recruited. Cone beam computed tomography data were obtained and soft tissue and bone shape reconstructions were performed. 3D models were created and surgical cuts were replicated according to postop scans. Each model was imported in ANSYS 2019R1 (Ansys Inc, USA) for simulation: the effect of variation in osteotomy plane as well as extent of bony segment movement were assessed by means of design of experiment: surgical parameters were varied in a surgically acceptable range and the soft tissue predictions were evaluated as displacement output of five craniometric landmarks. RESULTS: Simulation results show the overall changes of the lower third of the face are sensitive to changes in horizontal and vertical displacement of the bony segment as well as segment rotation. No significant changes in the soft tissue response were to attribute to the osteotomy design. CONCLUSIONS: Our results are consistent with experimental findings reported in the literature: when planning genioplasty in orthognathic surgery, particular focus on the segment movement (horizontal translation, vertical translation and rotation), rather than on the design of the osteotomy itself, should be considered.


Subject(s)
Genioplasty , Orthognathic Surgical Procedures , Cephalometry , Humans , Mandible , Retrospective Studies
14.
Med J Malaysia ; 76(4): 591-593, 2021 07.
Article in English | MEDLINE | ID: mdl-34305127

ABSTRACT

Acute pancreatitis (AP) is a serious condition that can occur suddenly in pregnancy. We present a case of sudden onset of epigastric pain with severely deranged serum triglyceride levels in a 32-year-old Vietnamese primigravida with no significant past medical history in the Singapore General Hospital. The patient was managed in the intensive care unit, with plasmapheres and intravenous insulin and was eventually a healthy term foetus was delievered via ceasarian section. This case showcased multidisciplinary co operation between the obstetrics, anaesthetic, endocrinology and intensive care team and serves as a reminder to consider this rare condition for future similar presentations.


Subject(s)
Pancreatitis , Acute Disease , Adult , Cesarean Section , Female , Humans , Pancreatitis/etiology , Pregnancy , Singapore , Tertiary Care Centers
15.
J Mech Behav Biomed Mater ; 113: 104120, 2021 01.
Article in English | MEDLINE | ID: mdl-33086137

ABSTRACT

OBJECTIVES: This study determined the effects of self-adhesive resin coatings on viscoelastic properties of highly viscous glass ionomer cements (HVGICs) using dynamic mechanical analysis. MATERIALS AND METHODS: The HVGICs evaluated were Zirconomer [ZR] (Shofu), Equia Forte [EQ] (GC) and Riva [RV] (SDI). Sixty specimens (12mm x 2mm x 2mm) of each material were fabricated using customized Teflon molds. After initial set, the specimens were removed from their molds, finished, measured and randomly divided into 3 groups of 20. Half the specimens in each group were left uncoated while the remaining half was covered with the respective manufacturers' resin coating. The specimens were subsequently conditioned in distilled water, artificial saliva or citric acid at 37°C for 7 days. The uncoated and coated specimens (n=10) were then subjected to dynamic mechanical testing in flexure mode at 37°C with a frequency of 0.1 to 10Hz. Storage modulus, loss modulus and loss tangent data were subjected to normality testing and statistical analysis using one-way ANOVA/Scheffe's post-hoc test and Ttest at significance level p<0.05. RESULTS: Mean storage modulus ranged from 1.39 ± 0.36 to 10.80 ± 0.86 GPa while mean loss modulus varied from 0.13 ± 0.03 to 0.70 ± 0.14 GPa after conditioning in the different mediums. Values for loss tangent ranged from 39.4 ± 7.75 to 213.2 ± 20.11 (x10 -3 ). Significant differences in visco-elastic properties were observed between mediums and materials. When conditioned in distilled water and artificial saliva,storage modulus was significantly improved when ZR, EQ and RV were uncoated. Significantly higher values were, however, observed with resin coating when the materials were exposed to citric acid. CONCLUSION: The visco-elastic properties of HVGICs were influenced by both resin coating and chemical environment.


Subject(s)
Glass Ionomer Cements , Water , Composite Resins , Materials Testing , Resin Cements , Saliva, Artificial , Viscosity
16.
Trop Med Int Health ; 25(10): 1235-1245, 2020 10.
Article in English | MEDLINE | ID: mdl-32737914

ABSTRACT

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.


OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.


Subject(s)
Child Health Services/statistics & numerical data , Early Diagnosis , HIV Infections/epidemiology , Point-of-Care Testing/statistics & numerical data , Quality Assurance, Health Care , Africa/epidemiology , Child Health Services/economics , Child Health Services/standards , Cost-Benefit Analysis , Female , HIV Infections/diagnosis , HIV Infections/economics , Humans , Infant , Infant, Newborn , Male , Point-of-Care Testing/economics , Point-of-Care Testing/standards
17.
Int J Obstet Anesth ; 43: 106-113, 2020 08.
Article in English | MEDLINE | ID: mdl-32439296

ABSTRACT

The use of extracorporeal membrane oxygenation (ECMO) as salvage therapy for patients with severe cardiopulmonary failure has increased significantly in the past decade. However, the use of ECMO in pregnant and peripartum patients has received scant attention. We performed a systematic review of case reports in the literature, documenting indications and outcomes of ECMO in pregnancy and postpartum patients. Case reports on ECMO use in pregnant and postpartum patients were retrieved from MEDLINE, EMBASE and SCOPUS databases up to December 2018. Ninety publications reporting on 97 patients met our inclusion criteria. The majority of publications reported peripartum or postpartum ECMO use for cardiovascular failure (60.8%), while the remainder had respiratory failure. Adult Respiratory Distress Syndrome (91.9%) was the most common respiratory indication while pulmonary embolism (23.7%) and peripartum cardiomyopathy (16.9%) accounted for the two most common cardiovascular indications. Hemorrhage was the most common complication of ECMO reported (31.9%). Of 96 documented neonatal outcomes, 80 neonates (83.3%) survived while 88 of 97 (90.7%) mothers survived. Extracorporeal membrane oxygenation appears to be a viable life support modality in pregnant and postpartum women with severe cardiopulmonary failure, but publication bias in our study cohort should be considered.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Heart Arrest/therapy , Pregnancy Complications, Cardiovascular/therapy , Puerperal Disorders/therapy , Female , Humans , Postpartum Period , Pregnancy
18.
J Laryngol Otol ; 134(12): 1103-1107, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33431081

ABSTRACT

OBJECTIVE: Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England. METHODS: The outcomes of T3 laryngeal carcinoma treatment at three centres (2007-2016) were retrospectively analysed using descriptive statistics and survival curves. RESULTS: Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy. CONCLUSION: Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.


Subject(s)
Carcinoma/therapy , Chemoradiotherapy/methods , Laryngeal Neoplasms/pathology , Laryngectomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Chemoradiotherapy/statistics & numerical data , England/epidemiology , Female , Humans , Laryngeal Neoplasms/mortality , Laryngectomy/statistics & numerical data , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/epidemiology , Radiotherapy/methods , Radiotherapy/statistics & numerical data , Survival Analysis , Survival Rate , Treatment Outcome , Young Adult
19.
Br J Dermatol ; 182(2): 434-443, 2020 02.
Article in English | MEDLINE | ID: mdl-31111470

ABSTRACT

BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.


Subject(s)
Nevus, Pigmented , Skin Neoplasms , Adult , Cohort Studies , Genotype , Humans , Male , Mutation/genetics , Nevus, Pigmented/genetics , Phenotype , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics
20.
Sci Rep ; 9(1): 18214, 2019 12 03.
Article in English | MEDLINE | ID: mdl-31796837

ABSTRACT

COPD is associated with disturbed tissue repair, possibly due to TGF-ß-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-ß-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-ß-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-ß-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-ß in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-ß-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-ß in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-ß-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.


Subject(s)
Airway Remodeling/genetics , Lung/pathology , MicroRNAs/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Transforming Growth Factor beta/metabolism , Aged , Cells, Cultured , Culture Media/metabolism , Down-Regulation , Female , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Regulation , Humans , Lung/cytology , Male , Middle Aged , Primary Cell Culture , Pulmonary Disease, Chronic Obstructive/genetics , RNA-Seq , Up-Regulation
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