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1.
PLoS One ; 19(4): e0298804, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574013

RESUMO

PURPOSE: The aim was to compare the probability of discharge after hip fracture surgery conditional on being alive and in hospital between patients mobilised within and beyond 36-hours of surgery across groups defined by depression. METHODS: Data were taken from the National Hip Fracture Database and included patients 60 years of age or older who underwent hip fracture surgery in England and Wales between 2014 and 2016. The conditional probability of postsurgical live discharge was estimated for patients mobilised early and for patients mobilised late across groups with and without depression. The association between mobilisation timing and the conditional probability of live discharge were also estimated separately through adjusted generalized linear models. RESULTS: Data were analysed for 116,274 patients. A diagnosis of depression was present in 8.31% patients. In those with depression, 7,412 (76.7%) patients mobilised early. In those without depression, 84,085 (78.9%) patients mobilised early. By day 30 after surgery, the adjusted odds ratio of discharge among those who mobilised early compared to late was 1.79 (95% CI: 1.56-2.05, p<0.001) and 1.92 (95% CI: 1.84-2.00, p<0.001) for those with and without depression, respectively. CONCLUSION: A similar proportion of patients with depression mobilised early after hip fracture surgery when compared to those without a diagnosis of depression. The association between mobilisation timing and time to live discharge was observed for patients with and without depression.


Assuntos
Fraturas do Quadril , Alta do Paciente , Humanos , Depressão/epidemiologia , Fraturas do Quadril/cirurgia , Fraturas do Quadril/diagnóstico , Modalidades de Fisioterapia , Inglaterra/epidemiologia
2.
Eur J Obstet Gynecol Reprod Biol ; 296: 239-243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484615

RESUMO

OBJECTIVES: To evaluate the association, if any, of homelessness or refuge accommodation on delivery and short term perinatal outcomes in an Irish tertiary maternity hospital. METHODS: A retrospective cohort study of 133 singleton pregnancies in women reporting to be homeless or living in refuge at their booking antenatal appointment between 2013 and 2022. Analysis compared sociodemographic characteristics and perinatal outcomes in this cohort to a reference population of 76,858 women with stable living arrangements. RESULTS: Women in the homeless/refuge population were statistically more likely to be single (75.2 % vs 39.5 %, p < 0.001), have an unplanned pregnancy (73.7 % vs 27.2 %, p < 0.001), report a history of psychiatric illness (42.9 % vs 22.4 %, p < 0.001), domestic violence (18.8 % vs 0.9 %, p < 0.001) alcohol consumption in pregnancy (3.0 % vs 0.8 %, p < 0.001) or smoking in pregnancy (41.3 % vs 9.7 %, p < 0.001). They were significantly more likely to have a preterm birth (adjusted OR 1.71 (1.01-2.87) p = 0.04). They also had a significantly lower median birth weight compared to the reference population (birthweight 3270 g vs 3420 g, p < 0.001). CONCLUSION: Women in the homeless and refuge population are more likely to experience poorer perinatal outcomes compared to women with stable living arrangements.


Assuntos
Pessoas Mal Alojadas , Gestantes , Campos de Refugiados , Humanos , Feminino , Gravidez , Adulto , Estudos Retrospectivos , Irlanda , Resultado da Gravidez , Nascimento Prematuro , Gravidez de Alto Risco
3.
Eur J Obstet Gynecol Reprod Biol ; 286: 90-94, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37229963

RESUMO

BACKGROUND: The UK and Ireland are facing significant challenges in the recruitment and retention of midwifery staff. Deficiencies in staffing, training and leadership have been cited as contributory factors to substandard care in both regional and global independent maternity safety reports. Locally, workforce planning is critical to maintaining 'one to one' care for all women in labor and to meet the peaks of daily birthing suite activity. OBJECTIVES: Analyze the variation in work intensity, defined by the mean number and range of births per midwifery working hours. METHODS: Retrospective observational study of birthing suite activity between 2017 and 2020. 30,550 singleton births were reported during the study period; however, 6529 elective Cesarean sections were excluded as these were performed during normal working hours by a separate operating theatre team. The times of 24,021 singleton births were organized into five proposed midwifery working rosters lasting eight or 12 h; A (00.00-07.59), B (08.00-15.59), C (16.00-23.59), D (20.00-0.759) and E (0.800-19.59). RESULTS: The number of births was comparable between the eight-hour and 12-hour work periods with a mean of five to six babies born per roster (range zero to 15). Work periods D and E lasting 12-hours both recorded a mean of eight births (range zero to 18). Hourly births ranged from a minimum of zero to a maximum of five births per hour (greater than seven times the mean), a number that was achieved 14 times during the study period. CONCLUSIONS: The mean number of births is consistent between normal working hours and unsociable 'on-call' periods, however there is an extreme range of activity within each midwifery roster. Prompt escalation plans remain essential for maternity services to manage unexpected increases in demand and complexity. WHAT IS ALREADY KNOWN ON THIS TOPIC: Shortfalls in staffing and inadequate workforce planning have been frequently cited in recent maternity safety reports as barriers to sustainable and safe maternity care. WHAT THIS STUDY ADDS: Our study shows that the mean number of births in a large tertiary center are consistent across day and night rosters. However, there are large fluctuations in activity during which births can exceed the number of available midwives. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Our study reflects the sentiments of the Ockenden review and APPG report on safe maternity staffing. Investment in services and the workforce to aid recruitment and reduce attrition is essential to establish robust escalation plans, including the deployment of additional staff in the event of extreme service pressures.


Assuntos
Trabalho de Parto , Serviços de Saúde Materna , Tocologia , Obstetrícia , Gravidez , Feminino , Humanos , Tocologia/educação , Recursos Humanos
4.
Eur J Obstet Gynecol Reprod Biol ; 285: 110-114, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37099860

RESUMO

BACKGROUND: Preterm deliveries account for 10% of all births, and are the most important cause of neonatal mortality globally. Despite their frequency, there is a paucity of information known about usual patterns of preterm labor, as previous studies which critically defined the normal progression of labor excluded preterm gestations. OBJECTIVE: To compare the durations of the first, second and third stages of spontaneous preterm labor in nulliparous and multiparous women at varying preterm gestations. METHODS: A retrospective observational study was undertaken of women admitted in spontaneous preterm labor from January 2017 to December 2020 with viable singleton gestations between 24 and 36 + 6 weeks' gestation who then proceeded to have a vaginal delivery. There were 512 cases following exclusion of preterm inductions of labor, instrumental vaginal deliveries, provider-initiated pre-labor Caesarean sections and emergency intrapartum Caesarean sections. The data was then examined to determine our outcomes of interest including the durations of the first, second and third stages of preterm labor, analyzing results by parity and gestation. For comparison, we reviewed data of term spontaneous labors and spontaneous vaginal deliveries during the same study period, identifying 8339 cases. FINDINGS: 97.6% of participants achieved a spontaneous cephalic vaginal delivery with the remainder undergoing an assisted breech birth. 5.7% of gestations delivered spontaneously between 24 + 0 and 27 + 6 weeks, with most births at gestations greater than 34 weeks (74%). The second stage duration (mean 15 vs 32 vs 32 mins respectively) was significantly different across the three gestation periods (p < 0.05), but was notably much quicker in extremely preterm labors. The first and third stage durations were similar between all gestational age groups with no statistically significant differences in results. There was a significant influence of parity on the first and second stages of labor, with multiparous women progressing more quickly than nulliparae (p < 0.001). CONCLUSION: The duration of spontaneous preterm labor is described. Multiparous women progress more quickly in the first and second stages of preterm labor than nulliparous women.


Assuntos
Trabalho de Parto , Trabalho de Parto Prematuro , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Parto Obstétrico , Maternidades , Estudos Observacionais como Assunto , Paridade , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
5.
Osteoporos Int ; 34(7): 1193-1205, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37016146

RESUMO

PURPOSE: This scoping review aimed to synthesise the available evidence on barriers and facilitators of weight bearing after hip fracture surgery in older adults. METHODS: Published (Cochrane Central, MEDLINE, EMBASE, CINAHL, and PEDro) and unpublished (Global Health, EThOS, WorldCat dissertation and thesis, ClinicalTrials.gov , OpenAIRE, DART-Europe) evidence was electronically searched from database inception to 29 March 2022. Barriers and facilitators of weight bearing were extracted and synthesised into patient, process (non-surgical), process (surgical), and structure-related barriers/facilitators using a narrative review approach. RESULTS: In total, 5594 were identified from the primary search strategy, 1314 duplicates were removed, 3769 were excluded on title and abstract screening, and 442 were excluded on full-text screening. In total, 69 studies (all from published literature sources) detailing 47 barriers and/or facilitators of weight bearing were included. Of barriers/facilitators identified, 27 were patient-, 8 non-surgical process-, 8 surgical process-, and 4 structure-related. Patient facilitators included anticoagulant, home discharge, and aid at discharge. Barriers included preoperative dementia and delirium, postoperative delirium, pressure sores, indoor falls, ventilator dependence, haematocrit < 36%, systemic sepsis, and acute renal failure. Non-surgical process facilitators included early surgery, early mobilisation, complete medical co-management, in-hospital rehabilitation, and patient-recorded nurses' notes. Barriers included increased operative time and standardised hip fracture care. Surgical process facilitators favoured intramedullary fixations and arthroplasty over extramedullary fixation. Structure facilitators favoured more recent years and different healthcare systems. Barriers included pre-holiday surgery and admissions in the first quarter of the year. CONCLUSION: Most patient/surgery-related barriers/facilitators may inform future risk stratification. Future research should examine additional process/structure barriers and facilitators amenable to intervention. Furthermore, patient barriers/facilitators need to be investigated by replicating the studies identified and augmenting them with more specific details on weight bearing outcomes.


Assuntos
Fraturas do Quadril , Humanos , Idoso , Fraturas do Quadril/cirurgia , Fraturas do Quadril/reabilitação , Suporte de Carga , Europa (Continente)
8.
Eur J Obstet Gynecol Reprod Biol ; 278: 137-140, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36174435

RESUMO

BACKGROUND: Trends in maternal demographic changes linked to lifestyle and socio-economic conditions reflect greatly on maternal, perinatal and infant mortality rates. Hospital data reflect a heterogenous population where specific demographic changes may not be obvious. OBJECTIVES: To report yearly demographic changes in Irish primiparae from 2000 to 2020, specifically looking at age, BMI, smoking and marital status of patients attending the Coombe Women and Infant's University Hospital (CWIUH). METHODS: Retrospective report of demographic details contemporaneously documented on the CWIUH data base. FINDINGS: In the years 2000 to 2020 inclusive there were 47,659 primiparous women of Irish ethnicity delivered at the CWIUH (70.2% of the total primiparae), of those 99.3% were Caucasian. There was a significant rise in mean age at first delivery in Irish mothers; 26.0 years old in the 2000 to 30.9 years old in 2020 associated with a rise in mean BMI of 9.1%. Smoking rates (ever smoked) showed a significant reduction from 53.9% in 2000 to 39.3% in 2020. There was a significant decrease in rates of marriage, with 61.9% married in 2000 compared to 46.3% in 2020. Birth weight and prematurity rates remained unchanged, with fall in mean gestational age at first delivery from 279.3 days in 2000 to 275.8 days in 2020. CONCLUSION: This study highlights that Irish primiparae are older, heavier, less likely to smoke and to be married than they were 20 years ago. These trends are an interesting glimpse into changing economic and cultural climate over just the past 2 decades.


Assuntos
Etnicidade , Recém-Nascido de Baixo Peso , Gravidez , Recém-Nascido , Lactente , Feminino , Humanos , Adulto , Estudos Retrospectivos , Mortalidade Infantil , Casamento
9.
BMC Geriatr ; 21(1): 537, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34627160

RESUMO

BACKGROUND: Patients with hip fracture and depression are less likely to recover functional ability. This review sought to identify prognostic factors of depression or depressive symptoms up to 1 year after hip fracture surgery in adults. This review also sought to describe proposed underlying mechanisms for their association with depression or depressive symptoms. METHODS: We searched for published (MEDLINE, Embase, PsychInfo, CINAHL and Web of Science Core Collection) and unpublished (OpenGrey, Greynet, BASE, conference proceedings) studies. We did not impose any date, geographical, or language limitations. Screening (Covidence), extraction (Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, adapted for use with prognostic factors studies Checklist), and quality appraisal (Quality in Prognosis Studies tool) were completed in duplicate. Results were summarised narratively. RESULTS: In total, 37 prognostic factors were identified from 12 studies included in this review. The quality of the underlying evidence was poor, with all studies at high risk of bias in at least one domain. Most factors did not have a proposed mechanism for the association. Where factors were investigated by more than one study, the evidence was often conflicting. CONCLUSION: Due to conflicting and low quality of available evidence it is not possible to make clinical recommendations based on factors prognostic of depression or depressive symptoms after hip fracture. Further high-quality research investigating prognostic factors is warranted to inform future intervention and/or stratified approaches to care after hip fracture. TRIAL REGISTRATION: Prospero registration: CRD42019138690 .


Assuntos
Depressão , Fraturas do Quadril , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Prognóstico
11.
Midwifery ; 102: 103079, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34246003

RESUMO

Interest in fear of childbirth has grown exponentially since the 1980s, but the landscape of birth has shifted considerably since then, with evolving feminism; moving from a patriarchal environment in a biomedical model of care to a holistic model which recognizes the birth and sexuality rights of women and birthing people. Distinguishing the spectrum of fear from low to high and severe is important rather than aggregating all individuals with fear of childbirth. However, the terms 'fear of childbirth' and 'tocophobia' have been used interchangeably. In this paper we urge clinicians to use the term 'tocophobia' with caution since it may be construed negatively and there is a limited understanding of the underpinning aetiology of tocophobia. Furthermore, using the label may be disempowering for women and birthing people making decisions about their birth. Further research is warranted to better understand the experience, refine and define the issue and meet the individual needs of people with fear of childbirth and tocophobia.


Assuntos
Idioma , Transtornos Fóbicos , Parto Obstétrico , Medo , Feminino , Humanos , Parto , Gravidez
12.
Clin Exp Dermatol ; 46(8): 1558-1560, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34137070

RESUMO

Pyoderma gangrenosum (PG) is an autoinflammatory neutrophilic dermatosis characterized by rapidly enlarging, painful ulcers. Anakinra is a recombinant interleukin (IL)-1 receptor antagonist that blocks the activity of IL-1α and IL-1ß by competitively inhibiting IL-1 binding to the IL-1 type 1 receptor. We present a series of two patients with recalcitrant PG, who had limited therapeutic options and multiple comorbidities and multiple previous treatment failures, who obtained 100% healing with anakinra. Compared with conventional first-line therapies for PG, the safety profile of anakinra may be preferable for patients with multiple comorbidities. Further research is needed to assess the safety and efficacy of anakinra for PG.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Idoso , Síndrome Antifosfolipídica/complicações , Artrite Reumatoide/complicações , Fármacos Dermatológicos/efeitos adversos , Dislipidemias/complicações , Feminino , Humanos , Hipertensão/complicações , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pessoa de Meia-Idade , Obesidade/complicações , Doenças Vasculares Periféricas/complicações , Pioderma Gangrenoso/complicações , Insuficiência Renal Crônica/complicações
13.
Clin Exp Dermatol ; 46(4): 720-722, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33639003

RESUMO

Full skin examination (FSE) may improve the detection of malignant melanoma (MM). The objective of this study was to assess the safety of targeted lesion examination (TLE) compared with FSE in our Pigmented Lesion Clinic (PLC). Patients attending the PLC were randomized in a 2 : 1 ratio to FSE (intervention) or TLE (standard care). Demographic details and risk factors were documented, and the time taken to perform FSE and TLE was noted. Of 763 participants, 520 were assigned to FSE and 243 were assigned to TLE. On average, FSE took 4.02 min and TLE took 30 s to perform. Of the 520 participants assigned to FSE, 37 (7.1%) had incidental findings, of whom 12 patients (2.3%) had additional lesions biopsied. No additional melanomas were detected that would have been missed by use of the standard protocol. This study suggests that in low-risk patients referred to a PLC with a lesion of concern, the possibility of missing incidental cutaneous malignancies using lesion-directed examination is low.


Assuntos
Melanoma/diagnóstico , Exame Físico/métodos , Neoplasias Cutâneas/diagnóstico , Adulto , Biópsia , COVID-19 , Dermatologia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Ausente , Fatores de Risco
14.
J Reprod Infant Psychol ; 39(1): 2-15, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33206580

RESUMO

Objective: To discuss and develop a statement on the current state of the evidence and opinion in Fear of Childbirth (FoC) and Tokophobia (Tocophobia), and to provide recommendations. Background: A group met in 2019 to discuss the state of clinical and academic knowledge relating to FoC/Tokophobia. Five key areas were agreed as the focus of the meeting. Methods: 12 internationally acknowledged experts, in this or a closely related area (e.g. PTSD) met to discuss their understanding of the evidence for FoC/ Tokophobia and current practice. The consensus described in this paper constitutes the expression of the general opinion of the participants and does not necessarily imply unanimity. Keys points: Work focussed on tokophobia is recent and there remains a wide range of issues, which were addressed in the workshop including complexity in defining prevalence, a theoretical lack of understanding, which creates challenge for robust assessment and the identification of risk factors. An improved aetiological and developmental understanding of the tokophobia is required to underpin appropriate, effective and evidence-based interventions. Evaluation of pathways of care and relevant interventions, should be a focus of future research. Conclusion: Significant gaps remain within the FoC/tokophobia knowledge base. Further research is necessary.


Assuntos
Parto Obstétrico/psicologia , Medo/psicologia , Transtornos Fóbicos/diagnóstico , Gestantes/psicologia , Consenso , Parto Obstétrico/normas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Transtornos Fóbicos/terapia , Gravidez , Apoio Social
15.
J Multidiscip Healthc ; 12: 855-869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695402

RESUMO

PURPOSE: Although rural and remote residents face general challenges accessing health care in comparison to urban dwellers, care for musculoskeletal conditions like chronic back disorders (CBD) is particularly challenging for rural and remote residents due to lack of access to physical yherapists. Telerehabilitation such as secure videoconferencing offers one solution to this disparity in rural care delivery, but incorporating the perspectives of health practitioners and patients is important when developing new sustainable care models. PATIENTS AND METHODS: This study investigated the experiences of practitioners and patients during a novel interprofessional model of assessment where an urban-based physical therapist used videoconferencing to virtually join a rural nurse practitioner and a rural patient with CBD. Patient surveys and semi-structured interviews of practitioners and patients were analyzed quantitatively and qualitatively. RESULTS: Most patients were "very satisfied" (62.1%) or "satisfied" (31.6%) with the overall experience, and "very" (63.1%) or "somewhat (36.9%) confident" with the assessment. Thematic analysis of interviews revealed that this novel assessment method identified: access to care for CBD, effective interprofessional practice, enhanced clinical care for CBD, and technology considerations. CONCLUSION: Patient satisfaction with the telerehabilitation model of care was high. Patients and practitioners reported their experiences were impacted by access to care, interprofessional practice, enhanced care for CBD and technology. These findings will be useful in the development of patient-centered models of care utilizing telehealth strategies.

17.
Ir Med J ; 110(7): 620, 2017 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-29169002

RESUMO

Aim The aim of this study was to assess skin cancer awareness and identify the UV protective measures used by golfers within the Munster region of Ireland. Methods Subjects were recruited from throughout the Munster region at a regional competition, and at three other local golf clubs and "pro" shops. Participants filled out a short anonymous validated questionnaire when collecting their score cards7. Results One hundred and sixty-three golfers completed the questionnaire with a mean age of 65.6 years. 137 (84%) were male and 26 (16%) were female. We noted a high incidence of both non-melanoma and melanoma skin cancer in our subjects. Sixteen (9.8%) had a previous history of skin cancer, with 8 melanomas and 8 non-melanoma skin cancers. A high percentage, 85%, of the golfers surveyed were compliant with SPF use. However many were using too low a SPF, 63 (44%) were using a SPF less than 30. Knowledge of risk of skin cancer is better amongst the golfers surveyed when compared to the general population. Most respondents (N = 96 (59%)) were aware that melanoma can lead to death if left untreated and 114 (70%) recognized that melanoma can be cured if treated early. Conclusion Golfers may benefit from targeted education emphasizing the importance of higher SPF use. Other interventions that may benefit this population would include availability of sunscreens and educational literature in 'pro' shops at golf courses.


Assuntos
Conscientização , Golfe/estatística & dados numéricos , Melanoma/epidemiologia , Melanoma/prevenção & controle , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/administração & dosagem , Idoso , Feminino , Educação em Saúde , Humanos , Irlanda/epidemiologia , Masculino , Inquéritos e Questionários
18.
BMC Geriatr ; 17(1): 125, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619010

RESUMO

BACKGROUND: One of the most common uses of the Internet is to search for health-related information. Although scientific evidence pertaining to cognitive health promotion has expanded rapidly in recent years, it is unclear how much of this information has been made available to Internet users. Thus, the purpose of our study was to assess the reliability and quality of information about cognitive health promotion encountered by typical Internet users. METHODS: To generate a list of relevant search terms employed by Internet users, we entered seed search terms in Google Trends and recorded any terms consistently used in the prior 2 years. To further approximate the behaviour of typical Internet users, we entered each term in Google and sampled the first two relevant results. This search, completed in October 2014, resulted in a sample of 86 webpages, 48 of which had content related to cognitive health promotion. An interdisciplinary team rated the information reliability and quality of these webpages using a standardized measure. RESULTS: We found that information reliability and quality were moderate, on average. Just one retrieved page mentioned best practice, national recommendations, or consensus guidelines by name. Commercial content (i.e., product promotion, advertising content, or non-commercial) was associated with differences in reliability and quality, with product promoter webpages having the lowest mean reliability and quality ratings. CONCLUSIONS: As efforts to communicate the association between lifestyle and cognitive health continue to expand, we offer these results as a baseline assessment of the reliability and quality of cognitive health promotion on the Internet.


Assuntos
Cognição , Promoção da Saúde/normas , Internet/normas , Ferramenta de Busca/normas , Promoção da Saúde/métodos , Humanos , Reprodutibilidade dos Testes , Ferramenta de Busca/métodos
20.
J Exp Med ; 214(3): 669-680, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28126831

RESUMO

Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-ß activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-ß signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative STAT3 mutations (STAT3mut ) or a loss-of-function mutation in ERBB2IP (ERBB2IPmut ) have evidence of deregulated TGF-ß signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-ß. In turn, cell-intrinsic deregulation of TGF-ß signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-ß pathway activation in ERBB2IPmut and STAT3mut patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Hipersensibilidade/imunologia , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Humanos , Interleucina-4/fisiologia , Receptores de Interleucina-4/fisiologia , Proteína Smad2/análise , Proteína Smad2/fisiologia , Proteína Smad3/análise , Proteína Smad3/fisiologia
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