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1.
Am J Physiol Lung Cell Mol Physiol ; 327(1): L65-L78, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651968

RESUMO

Perimenstrual worsening of asthma occurs in up to 40% of women with asthma, leading to increased acute exacerbations requiring clinical care. The role of sex hormones during these times remains unclear. In the current study, we used a translational approach to determine whether progesterone exacerbates allergic inflammation in the traditional chicken egg ovalbumin (OVA) model in BALB/c mice. Simultaneously, we used peripheral blood mononuclear cells (PBMC) from healthy human donors to assess the effects of progesterone on circulating group 2 innate lymphoid cells (ILC2). Briefly, lungs of ovariectomized (OVX) or sham-operated female (F-Sham) controls were implanted with a progesterone (P4, 25 mg) (OVX-P4) or placebo pellet (OVX-Placebo), followed by sensitization and challenge with ovalbumin (OVA). Progesterone increased total inflammatory histologic scores, increased hyper-responsiveness to methacholine (MCh), increased select chemokines in the bronchoalveolar lavage (BAL) and serum, and increased ILC2 and neutrophil numbers, along the airways compared with F-Sham-OVA and OVX-Placebo-OVA animals. Lung ILC2 were sorted from F-Sham-OVA, OVX-Placebo-OVA and OVX-P4-OVA treated animals and stimulated with IL-33. OVX-P4-OVA lung ILC2 were more responsive to interleukin 33 (IL-33) compared with F-Sham-OVA treated, producing more IL-13 and chemokines following IL-33 stimulation. We confirmed the expression of the progesterone receptor (PR) on human ILC2, and showed that P4 + IL-33 stimulation also increased IL-13 and chemokine production from human ILC2. We establish that murine ILC2 are capable of responding to P4 and thereby contribute to allergic inflammation in the lung. We confirmed that human ILC2 are also hyper-responsive to P4 and IL-33 and likely contribute to airway exacerbations following allergen exposures in asthmatic women with increased symptoms around the time of menstruation.NEW & NOTEWORTHY There is a strong association between female biological sex and severe asthma. We investigated the allergic immune response, lung pathology, and airway mechanics in the well-described chicken egg ovalbumin (OVA) model with steady levels of progesterone delivered throughout the treatment period. We found that progesterone enhances the activation of mouse group 2 innate lymphoid cells (ILC2). Human ILC2 are also hyper-responsive to progesterone and interleukin 33 (IL-33), and likely contribute to airway exacerbations following allergen exposures in women with asthma.


Assuntos
Asma , Pulmão , Linfócitos , Camundongos Endogâmicos BALB C , Ovalbumina , Progesterona , Progesterona/farmacologia , Animais , Feminino , Linfócitos/imunologia , Linfócitos/metabolismo , Humanos , Asma/imunologia , Asma/patologia , Asma/metabolismo , Camundongos , Ovalbumina/imunologia , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Imunidade Inata/efeitos dos fármacos , Interleucina-33/metabolismo , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Hipersensibilidade/metabolismo , Inflamação/patologia , Inflamação/imunologia , Inflamação/metabolismo , Modelos Animais de Doenças
2.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L683-L692, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726138

RESUMO

Nicotine of unprecedented concentrations and purity is being inhaled by those using commercially available electronic nicotine delivery systems (ENDS). The consequences of this route of self-administration on the immunological response to inhaled allergens are not known. In mice, sensitization and inhalation challenge with the common environmental house dust mite (HDM) allergen is an experimental model of this response. When mice were exposed to aerosolized nicotine base (aeroNic) twice daily, 5 days/wk for 8 wk, the HDM-induced recruitment of eosinophils (EOS) was substantially reduced as measured in bronchial alveolar lavage fluid (BALF). Oral nicotine administration had no effect. HDM challenge in the presence of nicotinic receptor subtype α7 (α7)-specific type-1 positive allosteric modulators (PAMs) was alone sufficient to suppress EOS. RNA analysis of alveolar macrophages (AM) collected from BALF after HDM challenge of aeroNic revealed that α7 activation strongly suppresses initiation of Ccl24 (eotaxin 2) transcription. To examine possible cellular signaling mechanisms coupling α7 to Ccl24 transcription, an AM culture model system was used. In AM cultures of freshly collected BALF, Ccl24 transcription was robustly activated by a mixture of IL-4 and IL-10, and this was suppressed by coapplication of type-1 PAMs through a pathway that requires p38MAPK but is independent of Jak2. These results suggest that the EOS response to HDM inhaled allergen is subject to modulation through activation of the α7 receptor and suggest that the allergic response may be substantially modified in ENDS users.


Assuntos
Antígenos de Dermatophagoides/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nicotina/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/metabolismo , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Pulmão/metabolismo , Camundongos , Ácaros , Nicotina/metabolismo , Pyroglyphidae/efeitos dos fármacos , Pyroglyphidae/imunologia
3.
Am J Physiol Lung Cell Mol Physiol ; 315(4): L553-L562, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29975102

RESUMO

Eosinophilia (EOS) is an important component of airway inflammation and hyperresponsiveness in allergic reactions including those leading to asthma. Although cigarette smoking (CS) is a significant contributor to long-term adverse outcomes in these lung disorders, there are also the curious reports of its ability to produce acute suppression of inflammatory responses including EOS through poorly understood mechanisms. One possibility is that proinflammatory processes are suppressed by nicotine in CS acting through nicotinic receptor α7 (α7). Here we addressed the role of α7 in modulating EOS with two mouse models of an allergic response: house dust mites (HDM; Dermatophagoides sp.) and ovalbumin (OVA). The influence of α7 on EOS was experimentally resolved in wild-type mice or in mice in which a point mutation of the α7 receptor (α7E260A:G) selectively restricts normal signaling of cellular responses. RNA analysis of alveolar macrophages and the distal lung epithelium indicates that normal α7 function robustly impacts gene expression in the epithelium to HDM and OVA but to different degrees. Notable was allergen-specific α7 modulation of Ccl11 and Ccl24 (eotaxins) expression, which was enhanced in HDM but suppressed in OVA EOS. CS suppressed EOS induced by both OVA and HDM, as well as the inflammatory genes involved, regardless of α7 genotype. These results suggest that EOS in response to HDM or OVA is through signaling pathways that are modulated in a cell-specific manner by α7 and are distinct from CS suppression.


Assuntos
Fumar Cigarros/imunologia , Pulmão/efeitos dos fármacos , Ovalbumina/toxicidade , Eosinofilia Pulmonar/prevenção & controle , Pyroglyphidae/patogenicidade , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Citocinas/metabolismo , Feminino , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/metabolismo , Eosinofilia Pulmonar/patologia , Receptor Nicotínico de Acetilcolina alfa7/genética
4.
Surg Endosc ; 31(12): 5248-5257, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28643051

RESUMO

BACKGROUND: The challenge of performing a good total mesorectal excision (TME) dissection, particularly in the distal 1/3 of the rectum, has spurred interest in new techniques. Robotic surgery is advocated by some, and more recently, a "new" approach, the transanal total mesorectal excision, has been popularized to address this problem. While great interest in this technique exists, little long-term outcome data are available. We have been utilizing a transanal abdominal transanal approach to TME in order to facilitate the distal dissection, and here, we provide our long-term outcomes using this approach in the management of rectal cancer. METHODS: From a prospectively maintained rectal cancer database, we identified 373 consecutive rectal cancers treated with sphincter preservation surgery through a combined transanal and abdominal approach to TME. Perioperative, pathological, and oncologic outcomes were analyzed. RESULTS: Three hundred and seventy-three patients with rectal cancer underwent a transanally initiated TME with mean follow-up of 5.5 years. 91% of cancers were in the distal rectum. 68.9% were men and 53.2% of cancers were tethered or fixed on presentation. 97.7% received neoadjuvant radiotherapy (mean 5405 cGy, 5-fluorouracil based); average time from completion of neoadjuvant therapy to surgery was 11 weeks. 180 and 193 patients underwent completion of their operation through open and laparoscopic abdominal approaches. 96% of TME specimens were complete/near complete, 94% had a negative circumferential resection margin, and 98.6% had a negative distal margin. Perioperative morbidity and mortality rates were 13.4 and 0.3%. Overall local recurrence (LR), DM, and Kaplan-Meier 5-year actuarial survival were 7.4, 19.5, and 90%, respectively. CONCLUSION: This is the first report of long-term data using a transanal approach to TME supporting this approach for rectal cancer. Our data with 5-year follow-up show that adequate distal and circumferential margins with very good-quality TME specimens, and a low risk for LR with excellent overall survival can be achieved using this technique. Our long-term results support the promising reports of early experiences in the literature.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica Transanal/métodos , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Neoplasias Retais/mortalidade , Reto/patologia , Reto/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Taxa de Sobrevida , Cirurgia Endoscópica Transanal/efeitos adversos , Resultado do Tratamento
6.
JAAPA ; 29(4): 34-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27023654

RESUMO

Survivors of critical illness may develop postintensive care syndrome (PICS), a spectrum of conditions that include persistent cognitive dysfunction, acquired weakness, and intrusive memories akin to post-traumatic stress disorder. Relatively few ICU survivors are routinely followed in the outpatient setting by intensivists, but are regularly evaluated by primary care physicians and physician assistants in their practices. Specific and focused education about the key features of PICS, its effect on patients as well as family members, and potential therapeutic interventions may increase recognition of PICS and reduce its effect on survivors of critical illness.


Assuntos
Cuidados Críticos/métodos , Estado Terminal/terapia , Unidades de Terapia Intensiva , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Sobreviventes/psicologia , Continuidade da Assistência ao Paciente , Estado Terminal/psicologia , Diagnóstico Tardio , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Síndrome
8.
Surg Endosc ; 29(9): 2763-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25480623

RESUMO

BACKGROUND: The utilization rates for minimally invasive colorectal resection techniques (MICR) continue to increase. In some centers MICR methods are the preferred approach, however, open methods continue to be utilized for select patients. In this study, the profile and short-term outcomes of open colorectal resection (CR) and MICR patients are determined and compared. METHODS: A retrospective review of patients who underwent elective CR over 11 years at two institutions was performed. The MICR group contained both laparoscopic-assisted and hand-assisted cases. The past medical and surgical histories, indications, operations performed, and short-term outcomes were assessed. The Charlson co-morbidity index (CMI) was used to assess risk. RESULTS: During the study period 1080 patients underwent CR (Open, 141; MICR, 939). As judged by the CMI, there were more high-risk patients (score ≥2) in the Open group (34.38%) versus MICR (22.11%) p = 0.0029. Significantly more open patients had prior abdominal surgery and specifically CRs (Open, 15.60% vs. MICR, 2.13%, p < 0.001). Intraoperative transfusion (Open 25.7%; MICR 6.8%, p < 0.001) and diversion (25.53 vs. 11.50%, p < 0.001) were more common in the Open group. Not surprisingly, recovery of bowel function and length of stay were longer for the Open group. The overall complication rate was also higher for the Open patients (p < 0.001). CONCLUSION: When MICR is the procedure of choice, patients selected for Open CR are higher risk and more complex as judged by the CMI and past operative history. Not surprisingly, this translates into a longer length of stay, higher rates of transfusion, diversion, and complications. This disparity in patients undergoing CRs makes direct comparison of MICR and Open resection outcomes not reasonable.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , Estudos Retrospectivos
9.
Dis Colon Rectum ; 57(6): 740-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24807599

RESUMO

BACKGROUND: Minimally invasive colorectal resection for cancer is associated with increased plasma levels of numerous proangiogenic proteins for 3 to 4 weeks postoperatively, and plasma from postoperative weeks 2 and 3 stimulates proangiogenic endothelial cell behavior in vitro. It is unknown if similar plasma changes occur after minimally invasive colorectal resection for benign pathology. OBJECTIVE: The aim of this study is to assess 1) plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 after minimally invasive colorectal resection for benign pathology and 2) postoperative plasma's effects on in vitro endothelial cell proliferation (branch point formation), migration, and invasion. DESIGN: Prospectively gathered plasma samples taken from patients undergoing colorectal resection who consented to participate in an institutional review board-approved plasma and data bank were used for ELISAs and in vitro endothelial cell studies. SETTINGS: The plasma and clinical data used were collected at 3 hospitals. PATIENTS: Patients undergoing minimally invasive colorectal resection for benign indications who were enrolled in a plasma/data bank and for whom adequate samples and volumes of plasma were available were included in the study. MAIN OUTCOME MEASURES: Perioperative plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were the primary outcomes measured. In vitro rates of endothelial cell branch point formation, migration, and invasion were determined after the addition of preoperative and postoperative plasma samples to endothelial cell cultures. RESULTS: Plasma from 86 patients undergoing minimally invasive colorectal resection for benign indications was assessed (diverticulitis, 30; benign polyps, 56). Plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were significantly increased for 3 to 4 weeks postoperatively compared with preoperative levels. In regard to the endothelial cell culture assays, significantly increased endothelial cell branch point formation, invasion, and migration results were noted with plasma from the second and third weeks postoperatively in comparison with preoperative culture results. LIMITATIONS: The weaknesses of this study are the limited numbers of late postoperative plasma samples and the need to bundle late samples into 7- to 12-day time blocks. CONCLUSIONS: Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma alterations similar to those found in patients who have cancer. Surgical trauma and not the indication is the likely cause.


Assuntos
Angiopoietina-2/sangue , Doenças do Colo/cirurgia , Diverticulite/cirurgia , Pólipos Intestinais/cirurgia , Proteínas da Gravidez/sangue , Doenças Retais/cirurgia , Molécula 1 de Adesão de Célula Vascular/sangue , Idoso , Movimento Celular , Células Cultivadas , Colo/cirurgia , Células Endoteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Neovascularização Fisiológica , Fator de Crescimento Placentário , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Reto/cirurgia
10.
Surg Endosc ; 28(1): 108-15, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23996331

RESUMO

BACKGROUND: Hand-assisted laparoscopic (HAL) colorectal resection remains controversial. Critics believe HAL methods lead to decreased use of laparoscopically assisted (LA) methods. Proponents believe selective HAL use increases minimally invasive surgery (MIS) use rates. This study assessed general and body mass index (BMI)-specific HAL and LA colorectal resection use by surgeons who embraced both methods. METHODS: This study retrospectively investigated 1,122 patients who underwent colorectal resection during an 8-year period. Surgical method, type of colorectal resection, BMI, comorbidities, incision length, and short-term outcomes were collected. RESULTS: The surgical methods included LA (60 %), HAL (25 %), and open (OP 15 %) procedures. The HAL group mean BMI was higher than that of the LA group (P < 0.0001), and the HAL use rate varied directly with BMI. The HAL technique was used for 48 % of the rectal, 36 % of the sigmoid, and 4 % of the right colorectal resections. The incision length was directly proportional to BMI for all the methods. Although the HAL incision lengths were significantly longer than the LA incision lengths for a BMI lower than 40 kg/m(2), there was no difference when the BMI was 40 kg/m(2) or higher. The comorbidities were greater in the HAL group than in the LA sigmoid colorectal resection group (P = 0.001). The mean hospital length of stay (LOS) was similar for the HAL and LA patients but longer for the open surgery patients (P < 0.0001 vs HAL group). The major complications, reoperations, and 30-day mortality rates were low and comparable. CONCLUSIONS: The HAL methods were used primarily for sigmoid and rectal colorectal resections and for higher BMI patients with more comorbidities. The mean incision length difference between the HAL and LA methods was 3.9 cm, but neither the LOS nor the major postoperative complications differed significantly. Selective use of HAL together with LA methods led to a MIS use rate of 85 % and facilitated MIS for high BMI patients. Together, the methods are complementary and may increase the number of minimally invasive surgeries performed.


Assuntos
Índice de Massa Corporal , Cirurgia Colorretal/métodos , Cirurgia Colorretal/estatística & dados numéricos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/epidemiologia , Doenças do Colo/cirurgia , Cirurgia Colorretal/mortalidade , Comorbidade , Feminino , Humanos , Laparoscopia/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Complicações Pós-Operatórias/mortalidade , Doenças Retais/epidemiologia , Doenças Retais/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Children (Basel) ; 11(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929281

RESUMO

The collection of papers in this Special Issue serves to extend the literature and evidence base for physical literacy (PL) research within child and youth populations. Currently, child and youth populations are increasingly sedentary, resulting in them spending less time engaging in daily physical activity (PA). Physical literacy serves as an attractive concept to help reframe and address physical inactivity and poor health and wellbeing, utilising a different and integrated approach to physical activity, health and wellbeing promotion. The studies presented in this Special Issue respond to previous calls in PL research for further empirical evidence, clarity around PL assessment, the utility of physical literacy with diverse populations including indigenous children and those with disabilities, the application of PL within early years, parental engagement and the role of physical education in the promotion of PL. These studies shed new light on the frontiers of PL research within child and youth populations.

13.
Viruses ; 16(3)2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543837

RESUMO

SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was defective in the early stages of the pandemic, leading to heightened and, sometimes, chronic inflammatory responses in the lungs. This lung-associated 'cytokine storm' or 'cytokine release syndrome' led to the need for oxygen supplementation, respiratory distress syndrome, and mechanical ventilation in a relatively high number of people. In this study, we evaluated circulating PBMC from non-hospitalized, male and female, COVID-19+ individuals over the course of infection, from the day of diagnosis (day 0) to one-week post diagnosis (day 7), and finally 4 weeks after diagnosis (day 28). In our early studies, we included hospitalized and critically care patient PBMC; however, most of these individuals were lymphopenic, which limited our assessments of their immune integrity. We chose a panel of 30 interferon-stimulated genes (ISG) to evaluate by PCR and completed flow analysis for immune populations present in those PBMC. Lastly, we assessed immune activation by stimulating PBMC with common TLR ligands. We identified changes in innate cells, primarily the innate lymphoid cells (ILC, NK cells) and adaptive immune cells (CD4+ and CD8+ T cells) over this time course of infection. We found that the TLR-7 agonist, Resiquimod, and the TLR-4 ligand, LPS, induced significantly better IFNα and IFNγ responses in the later phase (day 28) of SARS-CoV-2 infection in those non-hospitalized COVID-19+ individuals as compared to early infection (day 0 and day 7). We concluded that TLR-7 and TLR-4 agonists may be effective adjuvants in COVID-19 vaccines for mounting immunity that is long-lasting against SARS-CoV-2 infection.


Assuntos
COVID-19 , Humanos , Masculino , Feminino , SARS-CoV-2/genética , Pandemias , Imunidade Inata , Vacinas contra COVID-19 , Receptor 4 Toll-Like/genética , Leucócitos Mononucleares , Receptor 7 Toll-Like , Linfócitos , Interferons , Síndrome da Liberação de Citocina
14.
Cell Rep ; 43(7): 114365, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909363

RESUMO

Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation is recapitulated by adoptive transfer of fetal liver precursors following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, is concomitant with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a mechanism by which early-life inflammation results in increased asthma susceptibility in the presence of hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.


Assuntos
Imunidade Inata , Inflamação , Pulmão , Linfócitos , Animais , Pulmão/imunologia , Pulmão/patologia , Feminino , Linfócitos/imunologia , Inflamação/patologia , Inflamação/imunologia , Gravidez , Camundongos , Asma/imunologia , Asma/patologia , Camundongos Endogâmicos C57BL , Células Th2/imunologia
15.
Children (Basel) ; 10(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37761464

RESUMO

(1) Background: Physical literacy is increasing in popularity across the world as a concept central to the promotion of lifelong engagement in physical activity across a multitude of sectors. The education sector has embraced physical literacy as a concept worthy of focus. Physical literacy literature is bold in its claim that physical literacy should be the foundation of physical education. The objective of this paper was to understand the value of physical literacy as the goal of physical education through the lens of the capability approach; (2) Positioning: This research adopted a post-qualitative sensibility whereby knowledge is decentered, favoring the inseparability of ethics, ontology, and knowledge (ethico-onto-epistemology); (3) Discussion: Throughout the discussion, traditional humanist examples are extended to include post-humanism perspectives to offer a more holistic and ecological appreciation of the relationship between capabilities, physical literacy, and physical education, using the ten capabilities of life, bodily health, bodily integrity, senses, imagination and thought, emotions, practical reason, affiliation, other species, play, and control over one's environment; (4) Conclusions: The paper concludes with the recommendation that the capabilities approach offers a valuable framework for the continued justification of physical-literacy-enriched physical education, which, when aligned, can help to shape the opportunities provided for children and young people in support of their holistic development and lifelong engagement in physical activity.

16.
bioRxiv ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38045298

RESUMO

Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, and were associated with acute Th2 bias, eosinophilia, and decreased Tregs in the lung. The hyperactive ILC2 phenotype was recapitulated by adoptive transfer of a fetal liver precursor following exposure to prenatal inflammation, indicative of developmental programming. Programming of ILC2 function and subsequent lung immune remodeling by prenatal inflammation led to airway dysfunction at baseline and in response to papain, indicating increased asthma susceptibility. Our data provide a link by which developmental programming of progenitors by early-life inflammation drives lung immune remodeling and asthma susceptibility through hyperactivation of lung-resident ILC2s. One Sentence Summary: Prenatal inflammation programs asthma susceptibility by inducing the production of hyperactivated ILC2s in the developing lung.

17.
Front Sports Act Living ; 4: 853247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592588

RESUMO

The concept of physical literacy is continuing to gain traction internationally. This increasing interest has also given rise to concerns about the use, interpretation and meaning of the term "literacy" within the context of physical literacy. This paper explores the development of the terms literate, illiterate, literacy, and illiteracy identifying their historical origin and contemporary meaning. This provides the backdrop to explore the use of the term literacy within the context of physical literacy. In the final part of this introductory section the recent popularity of the literacies movement is explored. Our discussion identifies key intersections and areas of tension associated with the use, interpretation and meaning of literacy in the context of physical literacy. We adopt Whitehead's philosophy of physical literacy and discussion is informed further by Derrida's notion of differance, and Barad's challenge to singular representations of concepts. Once harnessing these concepts, we reach a juncture of an in-between space; entry points of nonidentity (sameness) and points where multiple effects of difference are created. Key discussion topics include: discourse, language and interpretations of literacy; in/tangibility of literacy; capturing literacy; literacy as a process or a product; connotations of the terms literate and illiterate; neoliberalism and literacy and finally literacy as learning. We believe that when understood as the productive and meaningful interaction with/in/through the world, literacy is still the appropriate term within the context of physical literacy. Our discussion leads us to conclude that as embodied individuals, physical literacy is often the literacy through which other literacies have to pass. Through physical activity individuals can not only nurture their own physical literacy but also contribute toward a global or holistic literacy that helps us navigate, connect and make sense of ourselves, others and the world around us. However, the paper acknowledges that this meaning is not always grasped with the historical understanding of literacy as well as it's translations into other languages presenting challenges in articulating the intended use, meaning and connotations of the contemporary understanding of physical literacy.

18.
J Clin Nurs ; 20(5-6): 723-32, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21320201

RESUMO

OBJECTIVES: The primary objective of the study was to determine which professional, situational and patient characteristics predict nurses' judgements of patient acuity and likelihood of referral for further review. A secondary aim was to test the feasibility of the factorial survey method in an acute area. BACKGROUND: There is increasing recognition that indicators of deterioration in acutely unwell adults are being missed and referrals delayed. The reasons for this are unclear and require exploration. Assessing nurses' clinical decision-making or judgements in a 'real-world' situation is problematic. DESIGN: The study used a factorial survey design where participants completed randomly generated paper-based vignettes on one occasion. METHODS: The dependent variables were assessment of patient acuity and likelihood of referral. Independent variables consisted of a number of patient characteristics, i.e. heart rate, blood pressure, nurse characteristics, i.e. clinical experience, and situational characteristics i.e. staffing. SETTING AND PARTICIPANTS: Participants were registered nurses working in acute areas excluding intensive care and theatre. Ninety-nine participants responded resulting in 1940 completed vignettes. RESULTS: An early warning score was the single most significant predictor of referral behaviour accounting for 9.6% of the variance. When this was not included in the vignette, nurses used physiological characteristics e.g. respiratory rate, urine output, neurological status. These explained 12% of the variance in the model predicting assessment of patient acuity and 9.4% or the variance predicting likelihood of referral. CONCLUSIONS: When given a series of vignettes, nurses appear to use appropriate physiological parameters to make decisions about patient acuity and need for referral. Our results support the use of early warning scoring systems. Education and professional development should focus more on developing and maximising clinical experience and expertise rather than knowledge acquisition alone. A factorial survey method is feasible to explore decision-making in this area. RELEVANCE TO PRACTICE: This study has several implications for practice. The emergence of an early warning scoring system as a significant individual predictor supports the use of such systems. However, the small amount of explained variance suggests that there are other influences on nurses' assessment of patient acuity and referral decisions that were not measured by the factorial survey approach. Educational provision might focus not just on knowledge acquisition but include educational delivery methods that incorporate or mimic real-ward settings.


Assuntos
Enfermagem , Doença Aguda , Adulto , Coleta de Dados , Humanos , Funções Verossimilhança
19.
Blood Adv ; 5(19): 3855-3861, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34570224

RESUMO

More than 20 years ago, clinical trials and federal grant support for sickle cell disease (SCD) research were not on par with support for other genetic diseases. Faced with the opportunity to spur research and advance treatments for SCD, and at the recommendation of advisors, the Doris Duke Charitable Foundation (DDCF) offered an SCD research funding opportunity starting in 2009 through its Innovations in Clinical Research Awards (ICRA) program. Twenty-eight new grants of $450 000 for direct costs over 3 years and 7 renewals were awarded, for a total investment of $17 million. Only about half the research teams garnered follow-on funding directly related to their ICRA projects, but the financial return on the research investment was substantial (∼4 times the original $17 million or 300%). All but 1 of the ICRA investigative teams published original research reports that acknowledged DDCF as a source of funding; the median number of publications per team was 3. Major innovations in the diagnosis and treatment of SCD included but were not limited to a demonstration that genetic modification of BCL11A enhancer is a potentially important treatment modality, establishment that plerixafor mobilization is safe and effective for those with SCD, development and validation of a new diagnostic called SCD BioChip, and evidence that hydroxyurea treatment is safe and efficacious in African children. These outcomes show that relatively small research grants can have a substantial return on investment and result in significant advances for a disease such as SCD.


Assuntos
Anemia Falciforme , Compostos Heterocíclicos , Anemia Falciforme/terapia , Organização do Financiamento , Mobilização de Células-Tronco Hematopoéticas , Humanos , Hidroxiureia
20.
Sports Med Open ; 7(1): 37, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34046703

RESUMO

BACKGROUND: Over the past decade, there has been increased interest amongst researchers, practitioners and policymakers in physical literacy for children and young people and the assessment of the concept within physical education (PE). This systematic review aimed to identify tools to assess physical literacy and its physical, cognitive and affective domains within children aged 7-11.9 years, and to examine the measurement properties, feasibility and elements of physical literacy assessed within each tool. METHODS: Six databases (EBSCO host platform, MEDLINE, PsycINFO, Scopus, Education Research Complete, SPORTDiscus) were searched up to 10th September 2020. Studies were included if they sampled children aged between 7 and 11.9 years, employed field-based assessments of physical literacy and/or related affective, physical or cognitive domains, reported measurement properties (quantitative) or theoretical development (qualitative), and were published in English in peer-reviewed journals. The methodological quality and measurement properties of studies and assessment tools were appraised using the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist. The feasibility of each assessment was considered using a utility matrix and elements of physical literacy element were recorded using a descriptive checklist. RESULTS: The search strategy resulted in a total of 11467 initial results. After full text screening, 11 studies (3 assessments) related to explicit physical literacy assessments. Forty-four studies (32 assessments) were relevant to the affective domain, 31 studies (15 assessments) were relevant to the physical domain and 2 studies (2 assessments) were included within the cognitive domain. Methodological quality and reporting of measurement properties within the included studies were mixed. The Canadian Assessment of Physical Literacy-2 and the Passport For Life had evidence of acceptable measurement properties from studies of very good methodological quality and assessed a wide range of physical literacy elements. Feasibility results indicated that many tools would be suitable for a primary PE setting, though some require a level of expertise to administer and score that would require training. CONCLUSIONS: This review has identified a number of existing assessments that could be useful in a physical literacy assessment approach within PE and provides further information to empower researchers and practitioners to make informed decisions when selecting the most appropriate assessment for their needs, purpose and context. The review indicates that researchers and tool developers should aim to improve the methodological quality and reporting of measurement properties of assessments to better inform the field. TRIAL REGISTRATION: PROSPERO: CRD42017062217.

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