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1.
J Urban Health ; 98(1): 111-129, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33108601

RESUMO

The methods used in low- and middle-income countries' (LMICs) household surveys have not changed in four decades; however, LMIC societies have changed substantially and now face unprecedented rates of urbanization and urbanization of poverty. This mismatch may result in unintentional exclusion of vulnerable and mobile urban populations. We compare three survey method innovations with standard survey methods in Kathmandu, Dhaka, and Hanoi and summarize feasibility of our innovative methods in terms of time, cost, skill requirements, and experiences. We used descriptive statistics and regression techniques to compare respondent characteristics in samples drawn with innovative versus standard survey designs and household definitions, adjusting for sample probability weights and clustering. Feasibility of innovative methods was evaluated using a thematic framework analysis of focus group discussions with survey field staff, and via survey planner budgets. We found that a common household definition excluded single adults (46.9%) and migrant-headed households (6.7%), as well as non-married (8.5%), unemployed (10.5%), disabled (9.3%), and studying adults (14.3%). Further, standard two-stage sampling resulted in fewer single adult and non-family households than an innovative area-microcensus design; however, two-stage sampling resulted in more tent and shack dwellers. Our survey innovations provided good value for money, and field staff experiences were neutral or positive. Staff recommended streamlining field tools and pairing technical and survey content experts during fieldwork. This evidence of exclusion of vulnerable and mobile urban populations in LMIC household surveys is deeply concerning and underscores the need to modernize survey methods and practices.


Assuntos
Características da Família , Pobreza , Adulto , Bangladesh/epidemiologia , Estudos de Viabilidade , Humanos , Inquéritos e Questionários
2.
Acta Derm Venereol ; 96(6): 774-8, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-26911400

RESUMO

A double-blind randomized controlled trial with a paired split-scar design compared verapamil, an L-type Ca2+ channel antagonist, and triamcinolone for prevention of keloid recurrence after excision. Ca2+ channel blocking activity of verapamil in keloid cells was explored. One keloid was excised per subject and each wound half randomized to receive intralesional injections of triamcinolone (10 mg/ml) or verapamil (2.5 mg/ml) at monthly intervals (4 doses). Interim analysis was performed after 14 subjects were completed. Survival analysis demonstrated significantly higher keloid recurrence with verapamil compared to triamcinolone 12 months post-surgery (log-rank test, p = 0.01) and higher overall risk of recurrence with verapamil (hazard ratio 8.44, 95% CI 1.62-44.05). The study was terminated early according to the stopping guideline (p < 0.05). Verapamil is safe but not as effective as triamcinolone in preventing keloid recurrence after excision. Further study is necessary to determine if clinical response to verapamil is linked to modulation of intracellular Ca2+.


Assuntos
Cicatriz/prevenção & controle , Glucocorticoides/uso terapêutico , Queloide/tratamento farmacológico , Queloide/cirurgia , Triancinolona Acetonida/uso terapêutico , Vasodilatadores/uso terapêutico , Verapamil/uso terapêutico , Adolescente , Adulto , Método Duplo-Cego , Feminino , Glucocorticoides/administração & dosagem , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagem , Vasodilatadores/administração & dosagem , Verapamil/administração & dosagem
3.
Glob Chang Biol ; 20(12): 3814-22, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24895112

RESUMO

Nutrient pollution presents a serious threat to biodiversity conservation. In terrestrial ecosystems, the deleterious effects of nitrogen pollution are increasingly understood and several mitigating environmental policies have been developed. Compared to nitrogen, the effects of increased phosphorus have received far less attention, although some studies have indicated that phosphorus pollution may be detrimental for biodiversity as well. On the basis of a dataset covering 501 grassland plots throughout Europe, we demonstrate that, independent of the level of atmospheric nitrogen deposition and soil acidity, plant species richness was consistently negatively related to soil phosphorus. We also identified thresholds in soil phosphorus above which biodiversity appears to remain at a constant low level. Our results indicate that nutrient management policies biased toward reducing nitrogen pollution will fail to preserve biodiversity. As soil phosphorus is known to be extremely persistent and we found no evidence for a critical threshold below which no environmental harm is expected, we suggest that agro-environmental schemes should include grasslands that are permanently free from phosphorus fertilization.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais/métodos , Fertilizantes/efeitos adversos , Pradaria , Fósforo/efeitos adversos , Poluentes do Solo/efeitos adversos , Solo/química , Europa (Continente) , Fertilizantes/análise , Geografia , Concentração de Íons de Hidrogênio , Modelos Teóricos , Fósforo/análise , Poluentes do Solo/análise
4.
Burns ; 50(7): 1871-1884, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38902133

RESUMO

After burn injury there is considerable variation in scar outcome, partially due to genetic factors. Scar vascularity is one characteristic that varies between individuals, and this study aimed to identify genetic variants contributing to different scar vascularity outcomes. An exome-wide array association study and gene pathway analysis was performed on a prospective cohort of 665 patients of European ancestry treated for burn injury, using their scar vascularity (SV) sub-score, part of the modified Vancouver Scar Scale (mVSS), as an outcome measure. DNA was genotyped using the Infinium HumanCoreExome-24 BeadChip, imputed to the Haplotype Reference Consortium panel. Associations between genetic variants (single nucleotide polymorphisms) and SV were estimated using an additive genetic model adjusting for sex, age, % total body surface area and number of surgical procedures, utilising linear and multinomial logistic regression. No individual genetic variants achieved the cut-off threshold for significance. Gene sets were also analysed using the Functional Mapping and Annotation (FUMA) platform, in which biological processes indirectly related to angiogenesis were significantly represented. This study suggests that SNPs in genes associated with angiogenesis may influence SV, but further studies with larger datasets are essential to validate these findings.


Assuntos
Queimaduras , Cicatriz , Polimorfismo de Nucleotídeo Único , População Branca , Humanos , Queimaduras/genética , Feminino , Masculino , Estudos Prospectivos , Adulto , Cicatriz/genética , Pessoa de Meia-Idade , População Branca/genética , Adulto Jovem , Modelos Logísticos , Estudos de Coortes , Idoso , Genótipo , Exoma/genética
5.
PLOS Glob Public Health ; 3(4): e0001824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068091

RESUMO

Infant and Young Child Feeding (IYCF) breastfeeding guidelines of the World Health Organization (WHO) have been promoted in Nepal since the early 1990s. This study investigated whether antenatal and perinatal service delivery in Nepal are associated with early initiation of breastfeeding and age-appropriate feeding practice (exclusive breastfeeding to six months; introduction of complementary foods at six months with continued breastfeeding to two years). Data from the 2016 Nepal Demographic and Health Survey (NDHS) were analysed using multivariable logistic regression. The unit of analysis was an interviewed woman and her last-born child aged 0-23 months. We examined number of antenatal visits, place and type of delivery, infant-mother skin-to-skin contact post-delivery, and breastfeeding observation and counselling by a healthcare provider within two days post-delivery. Of 1938 mother-infant dyads, 1073 (55.4%) commenced breastfeeding within one hour of delivery and 1665 (85.9%) were engaged in age-appropriate feeding. Breastfeeding within one hour of delivery was associated with infants delivered vaginally (aOR: 4.76, 95% CI: 2.96-7.65), infant-mother skin-to-skin contact post-delivery (aOR:2.10, 95% CI: 1.63-2.72) and observation of breastfeeding by a healthcare provider within two days post-delivery (aOR: 1.58, 95% CI: 1.20-2.08). Age-appropriate feeding was lowest amongst mothers with infants aged 4-5 months (40.8%) compared to those with infants aged 0-1 month (aOR: 0.158, 95% CI: 0.083-0.302). Antenatal and perinatal service delivery were not significantly associated with age-appropriate feeding. Further promotion of infant-mother skin-to-skin contact post-delivery (including after caesarean delivery) and observation of early breastfeeding may increase the rate of breastfeeding within one hour of delivery. Promotion of exclusive breastfeeding in antenatal and perinatal services and additional postnatal support should be considered to increase exclusive breastfeeding of infants to six months. These improvements may be achieved through enhanced implementation of the Baby Friendly Hospitals Initiative and effective training and sufficient practice for skilled birth attendants.

6.
J Invest Dermatol ; 142(5): 1489-1498.e12, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34687743

RESUMO

Scars are maintained for life and increase in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scars. In this study, we combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance. In total, 219 significantly differentially expressed and 1,199 significantly differentially methylated promoters were identified, of which there were 12 genes both significantly differentially methylated and expressed. Of these, the two transcription factors, FOXF2 and MKX, were selected for further analysis. Immunocytochemistry and qPCR suggested that FOXF2 but not MKX had elevated expression in scar fibroblasts. Using RNA sequencing, FOXF2 knockdown was shown to significantly reduce the expression of extracellular matrix‒related genes, whereas MKX did not appear to affect similar pathways. Finally, FOXF2 knockdown was also shown to significantly decrease collagen I production in scar and keloid fibroblasts. This study provides insights into the maintenance of normotrophic scar, suggesting that FOXF2 is an important regulator of this process. Targeting genes responsible for maintenance of scar phenotype may ameliorate scar appearance and improve patient outcomes in the future.


Assuntos
Cicatriz Hipertrófica , Queloide , Cicatriz Hipertrófica/patologia , Epigenoma , Fibroblastos/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Humanos , Queloide/patologia
7.
Int Wound J ; 8(5): 522-32, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21914133

RESUMO

Several different advanced treatments have been used to improve healing in chronic wounds, but none have shown sustained success. The application of topical growth factors (GFs) has displayed some potential, but the varying results, high doses and high costs have limited their widespread adoption. Many treatments have ignored the evidence that wound healing is driven by interactions between extracellular matrix proteins and GFs, not just GFs alone. We report herein that a clinical Good Manufacturing Practice-grade vitronectin:growth factor (cVN:GF) complex is able to stimulate functions relevant to wound repair in vitro, such as enhanced cellular proliferation and migration. Furthermore, we assessed this complex as a topical wound healing agent in a single-arm pilot study using venous leg ulcers, as well as several 'difficult to heal' case studies. The cVN:GF complex was safe and re-epithelialisation was observed in all but 1 of the 30 patients in the pilot study. In addition, the case studies show that this complex may be applied to several ulcer aetiologies, such as venous leg ulcers, diabetic foot ulcers and pressure ulcers. These findings suggest that further evaluation is warranted to determine whether the cVN:GF complex may be an effective topical treatment for chronic wounds.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Úlcera por Pressão/tratamento farmacológico , Úlcera Varicosa/tratamento farmacológico , Vitronectina/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Tópica , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Doença Crônica , Pé Diabético/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Projetos Piloto , Úlcera por Pressão/patologia , Resultado do Tratamento , Úlcera Varicosa/patologia
8.
Eur J Surg Oncol ; 47(3 Pt A): 545-550, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33218699

RESUMO

Older patients represent a growing proportion of the general surgical caseload. This includes those undergoing liver resection, with figures rising faster than the rate of population ageing. The physiology of ageing leads to changes in all body systems which may render the provision of safe anaesthesia more challenging than in younger patients. Anaesthesia for liver surgery has specific principles, largely aimed at reducing venous bleeding from the liver, and those related to complex major surgery. This review explores the principles of anaesthesia for liver resection and describes how they may require modification in the older patient. The traditional approach of low central venous pressure anaesthesia in order to reduce bleeding may need to be altered in the presence of a cardiovascular system less able to tolerate hypotension and hypoperfusion. These changes in physiology should also lower the threshold for invasive monitoring. The provision of effective analgesia perioperatively should be tailored to minimise the surgical stress response and opiate use. Careful consideration of general principles of intra-operative care for older patients, such as positioning, drug dosing, avoidance of excessively deep anaesthesia, and maintenance of normothermia are also important given the prolonged, complex nature of liver surgery. This individualised approach, with careful attention to changes in physiology allows liver resections to be undertaken in older patients without increases in mortality.


Assuntos
Anestesia Geral/métodos , Idoso Fragilizado , Hepatectomia , Cuidados Intraoperatórios , Idoso , Humanos
9.
PLOS Glob Public Health ; 1(11): e0000045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36962115

RESUMO

Smoking and hypertension are two major risk factors for cardiovascular disease, the leading cause of death in Nepal. The relationship between cigarette smoking and blood pressure (BP) in Nepal is unclear. This study analysed the data from the 2016 Nepal Demographic and Health Survey to explore the differences in systolic BP (SBP) and diastolic BP (DBP) between current daily cigarette smokers and non-smokers in Nepali adults aged 18 to 49 years. A total of 5518 women and 3420 men with valid BP measurements were included. Age, body mass index, wealth quintile (socio-economic status) and agricultural occupation (proxy for physical activity) were included as potential confounders in multivariable linear regression analysis. Women smokers were found to have significantly lower SBP (mean difference 2.8 mm, 95% CI 0.7-4.8 mm) and DBP (mean difference 2.2 mm, 95% CI 0.9-3.6 mm) than non-smokers after adjustment. There were no significant differences in BP between smokers and non-smokers in males, either before or after adjustment. The lower BP in female cigarette smokers in Nepal may be explained by the physiological effect of daily cigarette smoking per se in women, or unmeasured confounders associated with a traditional lifestyle that may lower BP (for example, diet and physical activity). In this nationally representative survey, daily cigarette smoking was not associated with increased BP in males or females in Nepal.

10.
PLoS One ; 16(3): e0249070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33755714

RESUMO

The time-critical 'can't intubate, can't oxygenate' [CICO] emergency post-induction of anaesthesia is rare, but one which, should it occur, requires Anaesthetists to perform rapid emergency front of neck access [FONA] to the trachea, restoring oxygenation, and preventing death or brain hypoxia. The UK Difficult Airway Society [DAS] has directed all Anaesthetists to be trained with surgical cricothyroidotomy [SCT] as the primary emergency FONA method, sometimes referred to as 'Cric' as a shorthand. We present a longitudinal analysis using a classical approach to Grounded Theory methodology of ten Specialist Trainee Anaesthetists' data during a 6-month training programme delivered jointly by Anaesthetists and Surgeons. We identified with a critical realist ontology and an objectivist epistemology meaning data interpretation was driven by participants' narratives and accepted as true accounts of their experience. Our theory comprises three themes: 'Identity as an Anaesthetist'; 'The Role of a Temporary Surgeon'; and 'Training to Reconcile Identities', whereby training facilitated the psychological transition from a 'bloodless Doctor' (Anaesthetist) to becoming a 'temporary Surgeon'. The training programme enabled Specialist Trainees to move between the role of control and responsibility (Identity as an Anaesthetist), through self-described 'failure' and into a role of uncertainty about one's own confidence and competence (The Role of a Temporary Surgeon), and then return to the Anaesthetist's role once the airway had been established. Understanding the complexity of an intervention and providing a better insight into the training needs of Anaesthetic trainees, via a Grounded Theory approach, allows us to evaluate training programmes against the recognised technical and non-technical needs of those being trained.


Assuntos
Anestesiologia/educação , Intubação Intratraqueal/métodos , Treinamento por Simulação , Adulto , Anestesiologistas/psicologia , Serviço Hospitalar de Emergência , Feminino , Teoria Fundamentada , Humanos , Estudos Longitudinais , Masculino
11.
Biomedicines ; 8(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650468

RESUMO

Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients' tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a 'scar-in-a-jar' model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.

12.
Biomedicines ; 8(7)2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32605309

RESUMO

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

13.
J Vasc Surg ; 50(4): 820-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19628362

RESUMO

BACKGROUND: The purpose of this study was to validate high-frequency ultrasound (HFU) measurement of dermal thickness for quantification of edema in patients with different severities of chronic venous disease. METHODS: HFU measurements of dermal thickness were made with a 17-MHz probe (Philips iU22 Ultrasound scanner, Bothell, Wash) or a 20-MHz medium-focus probe (DermaScan-C, Cortex Technology, Denmark), 7.5 cm above the medial malleolus. For validation, 20 patients with venous leg ulcers who were not receiving compression therapy, 20 patients with previous deep vein thrombosis (DVT) and symptoms of post-thrombotic syndrome (PTS) without ulceration, and 31 age-matched healthy controls were measured on a single occasion. To investigate the effect of compression on dermal thickness, the leg ulcer patients from the validation study were treated with compression therapy for 7 weeks and measured after 1, 3, 5, and 7 weeks. The association between dermal thickness and the clinical (C) component of the CEAP classification was examined in a cross-sectional analysis of 157 patients with a confirmed history of DVT >or=3 years ago. RESULTS: Dermal thickness in patients with venous leg ulcers before compression therapy (median, 2.56 mm; interquartile range [IQR], 2.31-2.82 mm) was significantly greater (P = .002) than that in patients with symptoms of PTS without ulceration (median, 2.16 mm; IQR, 1.90-2.36 mm). Dermal thickness in both groups was significantly greater (P < .0001) than the control group (median, 1.34 mm; IQR, 1.29-1.44 mm). Compression therapy caused a steady and significant decrease in dermal thickness during the first 5 weeks until normal control levels were achieved. Dermal thickness increased with increasing CEAP category. In 121 patients with a positive diagnosis of DVT >or=3 years ago from Radiology Department records, a hypothetical test cutoff of 1.985 mm for the prediction of severe PTS noted as C(4b), C(5), and C(6) (lipodermatosclerosis or leg ulceration) had a positive predictive value of 46.9% and a negative predictive value of 90.3%. CONCLUSION: HFU measurement of dermal thickness enables the monitoring of edema reduction by compression therapy. A prospective study is required to determine the temporal dynamics of dermal thickness changes after DVT and the relationship to the development of PTS. This test has the potential to be beneficial in the follow-up of patients after a DVT and provide clinical evidence for using graduated elastic compression stockings to control edema and prevent the development of more advanced skin changes.


Assuntos
Microscopia Acústica/normas , Síndrome Pós-Trombótica/diagnóstico por imagem , Síndrome Pós-Trombótica/terapia , Meias de Compressão , Úlcera Varicosa/diagnóstico por imagem , Úlcera Varicosa/terapia , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Microscopia Acústica/métodos , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Síndrome Pós-Trombótica/patologia , Probabilidade , Curva ROC , Valores de Referência , Índice de Gravidade de Doença , Pele/diagnóstico por imagem , Pele/patologia , Estatísticas não Paramétricas , Úlcera Varicosa/patologia
14.
Aust J Gen Pract ; 48(12): 883-889, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31774993

RESUMO

BACKGROUND AND OBJECTIVES: Data are sparse on how well the absolute risk approach is implemented in primary healthcare. The aim of this study was to quantify absolute cardiovascular disease (CVD) risk, appropriate use of blood pressure (BP)-lowering and lipid-lowering therapy, and clinical target responses in the Busselton baby boomer population. METHOD: This was a cross-sectional study of 5107 people aged 45-69 years (54.6% female) who participated in the 2010-2015 Busselton Healthy Ageing Study. RESULTS: Overall, 16.1% of participants had prior CVD (5.8%) or a high primary CVD risk (10.3%). The frequency of use of a guideline-recommended combination of BP-lowering and lipid-lowering therapy was 46.2% in participants with prior CVD, compared with only 16.8% in those with high primary CVD risk (P <0.001). Among the high-risk participants who were receiving recommended combination therapy, only 42.7% achieved target systolic BP levels and 42.1% achieved target total cholesterol levels. DISCUSSION: These data confirm substantial under treatment of Australian adults who are at high CVD risk. Enhanced implementation of absolute CVD risk assessment and evidence-based treatment in high-risk adults has potential for substantial health gains.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Fidelidade a Diretrizes/estatística & dados numéricos , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Idoso , Austrália , Doenças Cardiovasculares/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prevenção Primária , Prevenção Secundária , Austrália Ocidental
15.
Burns ; 45(3): 682-690, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30482614

RESUMO

Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2-/-, Ephrin-A5-/- and Ephrin-A2A5-/- transgenic mice, in vitro wound healing assays were conducted using isolated keratinocytes and fibroblasts. Ephrin-A2-/-, Ephrin-A2A5-/- and wild type mice with excisional wounds were used to analyze the impact of these ligands on wound closure, scar outcome, collagen orientation and re-innervation in vivo. The absence of the Ephrin-A2 and A5 ligands did not have any effect on dermal fibroblast proliferation or on fibroblast or keratinocyte migration. The loss of Ephrin-A2 and A5 ligands did not impact on the rate of wound closure or re-innervation after injury. However, changes in the gross morphology of the healed scar and in collagen histology of the scar dermis were observed in transgenic mice. Therefore Ephrin-A2 and A5 ligands may play an important role in final scar appearance associated with collagen deposition and structure.


Assuntos
Cicatriz/genética , Efrina-A2/genética , Efrina-A5/genética , Ferida Cirúrgica/patologia , Cicatrização/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Cicatriz/patologia , Colágeno , Fibroblastos , Queratinócitos , Camundongos , Camundongos Knockout , Camundongos Transgênicos
16.
Burns ; 45(3): 567-578, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30595539

RESUMO

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.


Assuntos
Queimaduras/terapia , Cicatriz Hipertrófica/genética , Cicatriz/genética , Adolescente , Adulto , Fenômenos Biomecânicos , Queimaduras/complicações , Adesão Celular/genética , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/fisiopatologia , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/fisiopatologia , Estudos de Coortes , Exoma , Feminino , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Estudos Prospectivos , População Branca , Adulto Jovem
17.
Int Wound J ; 5(1): 79-86, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18336381

RESUMO

In the wound bed of chronic venous leg ulcers, an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may cause excessive proteolysis and impair wound granulation. Soluble mediators in the wound environment may be responsible for this imbalance. The in vitro effect of wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1, MMP-3 and TIMP-1 was compared with the effect of acute wound fluid from two different sources: fluid from post-mastectomy axillary drains and fluid from skin graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by chronic venous leg ulcer wound fluid compared with both types of acute wound fluid (P < 0.005). Chronic venous ulcer wound fluid reduced TIMP-1 protein levels significantly more than acute graft fluid (P < 0.05). Venous ulcer wound fluid significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and reduced TIMP-1 production, confirming that mediators in the leg ulcer microenvironment can potentially induce excessive proteolysis in the ulcer dermis by altering the balance between MMPs and TIMPs. Inflammatory mediators including interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further work is required to confirm the factors responsible for the induction of a high MMP and low TIMP profile in fibroblasts by venous ulcer wound fluid.


Assuntos
Exsudatos e Transudatos/fisiologia , Fibroblastos/fisiologia , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Úlcera Varicosa/metabolismo , Idoso , Idoso de 80 Anos ou mais , Técnicas de Cultura de Células , Doença Crônica , Derme/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cicatrização/fisiologia , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/metabolismo
18.
Burns ; 44(7): 1792-1800, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30072196

RESUMO

Burn scars can be associated with significant loss of cutaneous sensation, paresthesia and chronic pain. Long-term systemic changes in cutaneous innervation may contribute to these symptoms and dorsal root ganglia have been implicated in the development of chronic neuropathic pain. Therefore we hypothesized that changes in cutaneous innervation after burn injury may be mediated at the level of the dorsal root ganglia. Burn group rats (n=20) were subjected to a unilateral burn injury while 12 control rats underwent sham procedure. The DRGs dermatomally related to the site of burn (Thoracic 13, lumbar 1 and lumbar 2), ipsilateral and contralateral to the injury, were compared for Type A, Type B and total cell number with sham control DRGs, at 4 and 6 weeks after injury. There was a significant decrease in Type A cell count (cell bodies of nerve fibres mediating touch-pressure-vibration sensation) in the 4 week time-point group (p=0.0124) ipsilateral to the burn injury. Total DRG cell count and Type B DRG cell count (cell bodies of fibres mediating pain and itch) on the ipsilateral side was not significantly altered. On the side contralateral to the burn injury, there was no statistically significant change in the total cell count, Type A cell count or Type B cell count. This data showed a decrease in Type A cell number in DRGs after a burn injury, suggesting cell death may mediate some changes observed in cutaneous innervation after a burn. Type B cells constituted a greater proportion of the viable cell population in the ipsilateral DRG after a burn injury. This change may be important in the induction of signalling related to pain and itch and has important implications for the restoration of normal cutaneous innervation after burn injury. Investigating whether neuro-protective or neuro-restorative approaches can ameliorate damage to the DRG will be important to improve sensory outcomes for burn patients.


Assuntos
Queimaduras/patologia , Morte Celular , Gânglios Espinais/patologia , Células Receptoras Sensoriais/patologia , Pele/inervação , Animais , Contagem de Células , Gânglios Espinais/citologia , Neuralgia , Dor , Prurido , Ratos , Células Receptoras Sensoriais/citologia , Pele/lesões , Tato
19.
BMJ Open ; 8(7): e024101, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30068626

RESUMO

INTRODUCTION: Lack of safe, stimulating and health-promoting environments for children under-5 hinders their physical, social and cognitive development, known as early childhood development (ECD). Improving ECD impacts on children, and can improve educational attainment for girls, who often care for younger siblings, and employment prospects for mothers. Developing and evaluating the impacts of ECD programmes within childcare needs to assess a range of social, health, educational and economic impacts, including women's empowerment.Children living in slums are at high risk of poor early development and holistic, sustainable interventions are needed to address ECD in these contexts. This study will be undertaken in Dhaka, Bangladesh, a city where over 8.5 million inhabitants live in slums. In collaboration with government, non-governmental organisations and communities, we are developing and testing a sustainable day-care model for low-income communities in Dhaka. METHODOLOGY AND ANALYSIS: A sequential mixed methods approach is being used in the study, with qualitative work exploring quantitative findings. Two hundred households with children under-5 will be surveyed to determine day-care needs and to assess ECD (parent-reported and direct assessment). The feasibility of four ECD measuring tools Caregiver-Reported Early Development Index, Measuring Early Learning Quality and Outcomes, The Early Human Capability Index and International Development and Early Learning Assessment will be assessed quantitatively and qualitatively. Qualitative methods will help understand demand and perceptions of day care while mothers work. Participatory action research will be used to develop a locally appropriate and potentially sustainable model of day care for under-5 children. A ward in the south of Dhaka has been selected for the study as this typifies communities with slum and non-slum households living next to each other, allowing us to explore potential for better-off household to subsidise day care for poorer households. ETHICS AND DISSEMINATION: Findings will be published and inform decision makers at the national, regional and the local actors in order to embed the study into the policy and practice on childcare and ECD. Ethical approvals for this study were obtained from the School of Medicine Research Ethics Committee at the Faculty of Medicine and Health at the University of Leeds (ref: MREC16-106) and the Bangladesh Medical Research Council (ref: BMRCAIREC/20 I 6-20 I 9 I 250).


Assuntos
Cuidado da Criança , Desenvolvimento Infantil , Áreas de Pobreza , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Bangladesh , Pré-Escolar , Educação , Emprego , Estudos de Viabilidade , Feminino , Humanos , Lactente , Mães , Avaliação das Necessidades , Pobreza , População Urbana
20.
BMJ Open ; 8(11): e024182, 2018 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-30478123

RESUMO

INTRODUCTION: As rapid urbanisation transforms the sociodemographic structures within cities, standard survey methods, which have remained unchanged for many years, under-represent the urban poorest. This leads to an overly positive picture of urban health, distorting appropriate allocation of resources between rural and urban and within urban areas. Here, we present a protocol for our study which (i) tests novel methods to improve representation of urban populations in household surveys and measure mental health and injuries, (ii) explores urban poverty and compares measures of poverty and 'slumness' and (iii) works with city authorities to understand, and potentially improve, utilisation of data on urban health for planning more equitable services. METHODS AND ANALYSIS: We will conduct household surveys in Kathmandu, Hanoi and Dhaka to test novel methods: (i) gridded population sampling; (ii) enumeration using open-access online maps and (iii) one-stage versus two-stage cluster sampling. We will test reliability of an observational tool to categorise neighbourhoods as slum areas. Within the survey, we will assess the appropriateness of a short set of questions to measure depression and injuries. Questionnaire data will also be used to compare asset-based, consumption-based and income-based measures of poverty. Participatory methods will identify perceptions of wealth in two communities in each city. The analysis will combine quantitative and qualitative findings to recommend appropriate measures of poverty in urban areas. We will conduct qualitative interviews and establish communities of practice with government staff in each city on use of data for planning. Framework approach will be used to analyse qualitative data allowing comparison across city settings. ETHICS AND DISSEMINATION: Ethical approvals have been granted by ethics committees from the UK, Nepal, Bangladesh and Vietnam. Findings will be disseminated through conference papers, peer-reviewed open access articles and workshops with policy-makers and survey experts in Kathmandu, Hanoi and Dhaka.


Assuntos
Disparidades nos Níveis de Saúde , Vigilância em Saúde Pública/métodos , Inquéritos e Questionários , Adulto , Idoso , Ásia , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e Questionários/economia , Inquéritos e Questionários/normas , População Urbana , Adulto Jovem
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