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1.
Mol Med ; 30(1): 115, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112965

RESUMO

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.


Assuntos
Biomarcadores , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Modelos Animais de Doenças , Células Estreladas do Pâncreas , Fibrose Cística/genética , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Animais , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Feminino , Ovinos , Pâncreas/metabolismo , Pâncreas/patologia , Gravidez , Pancreatopatias/genética , Pancreatopatias/metabolismo , Pancreatopatias/patologia , Transcriptoma , Humanos , Perfilação da Expressão Gênica
2.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000103

RESUMO

The number of people diagnosed with type 2 diabetes is on the increase worldwide. Of growing concern, the prevalence of type 2 diabetes in children and youths is increasing rapidly and mirrors the increasing burden of childhood obesity. There are many risk factors associated with the condition; some are due to lifestyle, but many are beyond our control, such as genetics. There is an urgent need to develop better therapeutics for the prevention and management of this complex condition since current medications often cause unwanted side effects, and poorly managed diabetes can result in the onset of related comorbidities. Naturally derived compounds have gained momentum for preventing and managing several complex conditions, including type 2 diabetes. Here, we provide an update on the benefits and limitations of fenugreek and its components as a therapeutic for type 2 diabetes, including its bioavailability and interaction with the microbiome.


Assuntos
Diabetes Mellitus Tipo 2 , Extratos Vegetais , Trigonella , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Trigonella/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Animais , Microbioma Gastrointestinal/efeitos dos fármacos
3.
Nurs Outlook ; 72(3): 102148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38417205

RESUMO

BACKGROUND/PURPOSE: This paper describes the origins of the Boston Training School for Nurses (1873), later named the Massachusetts General Hospital School of Nursing, and the role played by a Boston civic group, the Woman's Education Association, in its founding. METHODS: Social and political forces in the post-Civil War modern era and the challenges the founders encountered in establishing and managing a nursing school are delineated. DISCUSSION: Themes that highlight the significance of the Boston Training School's creation relative to the nurse training movement in America are identified. CONCLUSION: The long-term implications of the initial agreement for a 1-year experiment to train nurses in a formal educational setting are discussed.


Assuntos
Escolas de Enfermagem , Boston , Humanos , História do Século XIX , História do Século XX , Educação em Enfermagem
4.
Funct Integr Genomics ; 23(2): 135, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37085733

RESUMO

The precise molecular events initiating human lung disease are often poorly characterized. Investigating prenatal events that may underlie lung disease in later life is challenging in man, but insights from the well-characterized sheep model of lung development are valuable. Here, we determine the transcriptomic signature of lung development in wild-type sheep (WT) and use a sheep model of cystic fibrosis (CF) to characterize disease associated changes in gene expression through the pseudoglandular, canalicular, saccular, and alveolar stages of lung growth and differentiation. Using gene ontology process enrichment analysis of differentially expressed genes at each developmental time point, we define changes in biological processes (BP) in proximal and distal lung from WT or CF animals. We also compare divergent BP in WT and CF animals at each time point. Next, we establish the developmental profile of key genes encoding components of ion transport and innate immunity that are pivotal in CF lung disease and validate transcriptomic data by RT-qPCR. Consistent with the known pro-inflammatory phenotype of the CF lung after birth, we observe upregulation of inflammatory response processes in the CF sheep distal lung during the saccular stage of prenatal development. These data suggest early commencement of therapeutic regimens may be beneficial.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Pulmão , Animais , Fibrose Cística/genética , Fibrose Cística/patologia , Fibrose Cística/veterinária , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Perfilação da Expressão Gênica , Pulmão/crescimento & desenvolvimento , Pulmão/metabolismo , Ovinos/genética , Transcriptoma , Inflamação/genética , Inflamação/patologia
5.
Mol Biol Rep ; 50(3): 2471-2478, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36600108

RESUMO

BACKGROUND: Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group. METHODS AND RESULTS: Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin. COVID-19 patients had higher serum levels of ferritin than those levels in control group (P < 0.0001). Conversely levels of HIF-1α and HEPH in the COVID-19 group were significantly lower than those of control group (P < 0.0001 for both). An inverse correlation between hephaestin and ferritin as well as between HIF-1α and ferritin was found among all subjects (P < 0.0001), and among COVID-19 patients, but not to statistical significance. CONCLUSION: Levels of hephaestin and HIF-1α were found to be inversely related levels of ferritin across all participants in the study, and to our knowledge this is the first report of hephaestin and HIF-1α as potential markers of iron status. Further studies are needed to corroborate the findings, utilizing a broader range of markers to monitor inflammatory as well as iron status.


Assuntos
COVID-19 , Ferritinas , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ferro/metabolismo , Estudos Prospectivos , SARS-CoV-2/metabolismo
6.
Reprod Fertil Dev ; 35(11): 575-588, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37308165

RESUMO

CONTEXT: In vitro maturation is an important process in the production of embryos. It has been shown that three cytokines, fibroblast growth factor 2, leukemia inhibitory factor and insulin-like growth factor 1 (FLI), increased efficiency of in vitro maturation, somatic cell nuclear transfer (SCNT) blastocyst production, and in vivo development of genetically engineered piglets. AIMS: Assess effects of FLI on oocyte maturation, quality of oocytes, and embryo development in bovine in vitro fertilisation (IVF) and SCNT. KEY RESULTS: Cytokine supplementation resulted in significant increases in maturation rates and decreased levels of reactive oxygen species. Oocytes matured in FLI had increased blastocyst rates when used in IVF (35.6%vs 27.3%, P <0.05) and SCNT (40.6%vs 25.7%, P <0.05). SCNT blastocysts contained significantly more inner cell mass and trophectodermal cells when compared to the control group. Importantly, SCNT embryos derived from oocytes matured in FLI medium resulted in a four-fold increase in full-term development compared to control medium (23.3%vs 5.3%, P <0.05). Relative mRNA expression analysis of 37 genes associated with embryonic and fetal development revealed one gene had differential transcript abundance in metaphase II oocytes, nine genes at the 8-cell stage, 10 genes at the blastocyst stage in IVF embryos and four genes at the blastocyst stage in SCNT embryos. CONCLUSIONS: Cytokine supplementation increased efficiency of in vitro production of IVF and SCNT embryos and in vivo development of SCNT embryos to term. IMPLICATIONS: Cytokine supplementation is beneficial to embryo culture systems, which may shed light on requirements of early embryo development.


Assuntos
Citocinas , Técnicas de Transferência Nuclear , Animais , Bovinos , Suínos , Citocinas/genética , Citocinas/metabolismo , Técnicas de Transferência Nuclear/veterinária , Desenvolvimento Embrionário , Fertilização in vitro/veterinária , Blastocisto/metabolismo , Oócitos/metabolismo , Suplementos Nutricionais , Clonagem de Organismos
7.
Kidney Int ; 102(2): 261-279, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35513125

RESUMO

Fibroblast growth factor (FGF) 23 is a phosphate-regulating hormone that is elevated in patients with chronic kidney disease and associated with cardiovascular mortality. Experimental studies showed that elevated FGF23 levels induce cardiac hypertrophy by targeting cardiac myocytes via FGF receptor isoform 4 (FGFR4). A recent structural analysis revealed that the complex of FGF23 and FGFR1, the physiologic FGF23 receptor in the kidney, includes soluble α-klotho (klotho) and heparin, which both act as co-factors for FGF23/FGFR1 signaling. Here, we investigated whether soluble klotho, a circulating protein with cardio-protective properties, and heparin, a factor that is routinely infused into patients with kidney failure during the hemodialysis procedure, regulate FGF23/FGFR4 signaling and effects in cardiac myocytes. We developed a plate-based binding assay to quantify affinities of specific FGF23/FGFR interactions and found that soluble klotho and heparin mediate FGF23 binding to distinct FGFR isoforms. Heparin specifically mediated FGF23 binding to FGFR4 and increased FGF23 stimulatory effects on hypertrophic growth and contractility in isolated cardiac myocytes. When repetitively injected into two different mouse models with elevated serum FGF23 levels, heparin aggravated cardiac hypertrophy. We also developed a novel procedure for the synthesis and purification of recombinant soluble klotho, which showed anti-hypertrophic effects in FGF23-treated cardiac myocytes. Thus, soluble klotho and heparin act as independent FGF23 co-receptors with opposite effects on the pathologic actions of FGF23, with soluble klotho reducing and heparin increasing FGF23-induced cardiac hypertrophy. Hence, whether heparin injections during hemodialysis in patients with extremely high serum FGF23 levels contribute to their high rates of cardiovascular events and mortality remains to be studied.


Assuntos
Fator de Crescimento de Fibroblastos 23 , Heparina , Proteínas Klotho , Insuficiência Renal Crônica , Animais , Cardiomegalia , Glucuronidase/metabolismo , Heparina/metabolismo , Humanos , Proteínas Klotho/metabolismo , Camundongos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
8.
Curr Opin Nephrol Hypertens ; 31(4): 320-325, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703246

RESUMO

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a progressive disorder that is associated with development of elevated fibroblast growth factor 23 (FGF23) levels and anemia. Here, we review recent literature that extends our current knowledge on the interactions between FGF23 and anemia in CKD and the impact of anemia-targeting therapeutics on FGF23 elevation in CKD. RECENT FINDINGS: The anemia of CKD is primarily driven by a lack of erythropoietin (EPO) and iron deficiency. In addition to EPO and iron replacement, novel drug classes to treat anemia have been approved or are in clinical development. A recent observational study provides supportive evidence for the hypothesis that FGF23 elevation in CKD mediates adverse effects of iron deficiency on the cardiovascular system in patients with CKD. Preclinical and clinical studies revealed that ferric citrate (FC), and hypoxia-induced factor-prolyl hydroxylase inhibitor (HIF-PHI) treatment may reduce elevated FGF23 levels in CKD, suggesting that correcting anemia in CKD could potentially lower FGF23 levels. However, as we describe, HIF-PHI have context-dependent effects. Moreover, whether a reduction in FGF23 will improve patient outcomes in patients with CKD remains to be determined. SUMMARY: With the emergence of novel therapeutics to treat oxygen and iron utilization deficits in CKD, studies have investigated the impact of these new drugs on FGF23. Several of these drugs, including FC and HIF-PHIs, alleviate iron homeostasis alterations in CKD and are associated with FGF23 reduction. Herein, we review the relationships between oxygen/iron sensing and FGF23 in CKD, recent findings which link FGF23 with cardiac dysfunction, as well as future translational and clinical avenues.


Assuntos
Anemia , Insuficiência Renal Crônica , Anemia/tratamento farmacológico , Anemia/etiologia , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Homeostase , Humanos , Ferro/uso terapêutico , Oxigênio , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo
9.
J Nurs Adm ; 52(6): 338-344, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35536875

RESUMO

OBJECTIVE: The aim of this study was to evaluate programmatic elements supporting BSN attainment by employed nurses holding associate degrees or diplomas, using a stakeholder involvement approach. BACKGROUND: Studies have associated higher percentages of baccalaureate-prepared nurses with improved clinical outcomes. Since 2013, the study organization supported an RN-to-BSN requirement with an academic progression benefit program and achieved an 80% BSN goal by 2021. METHODS: The Centers for Disease Control and Prevention's Framework for Program Evaluation was used. A mixed methods approach was orchestrated by a stakeholder team to explore use and importance of programmatic elements, and motivators and barriers for degree attainment, using an online survey and focus groups. RESULTS: Respondents revealed a significant association between BSN degree attainment and financial assistance and perceived importance of financial assistance and educational fairs. CONCLUSIONS: Validating organizational tactics is important for achieving increased numbers of baccalaureate-prepared nurses and supportive of the cost-effective use of resources.


Assuntos
Bacharelado em Enfermagem , Grupos Focais , Humanos , Motivação , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
10.
Clin Infect Dis ; 73(9): e3563-e3571, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33372989

RESUMO

BACKGROUND: At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. METHODS: We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. RESULTS: Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants. CONCLUSIONS: An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.


Assuntos
Infecções por HIV , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Estudos de Coortes , Diarilquinolinas/efeitos adversos , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Retrospectivos , Rifampina , África do Sul/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
11.
Kidney Int ; 99(3): 598-608, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33159963

RESUMO

Fibroblast Growth Factor 23 (FGF23) is a bone-derived hormone that reduces kidney phosphate reabsorption and 1,25(OH)2 vitamin D synthesis via its required co-receptor alpha-Klotho. To identify novel genes that could serve as targets to control FGF23-mediated mineral metabolism, gene array and single-cell RNA sequencing were performed in wild type mouse kidneys. Gene array demonstrated that heparin-binding EGF-like growth factor (HBEGF) was significantly up-regulated following one-hour FGF23 treatment of wild type mice. Mice injected with HBEGF had phenotypes consistent with partial FGF23-mimetic activity including robust induction of Egr1, and increased Cyp24a1 mRNAs. Single cell RNA sequencing showed overlapping HBEGF and EGF-receptor expression mostly in the proximal tubule, and alpha-Klotho expression in proximal and distal tubule segments. In alpha-Klotho-null mice devoid of canonical FGF23 signaling, HBEGF injections significantly increased Egr1 and Cyp24a1 with correction of basally elevated Cyp27b1. Additionally, mice placed on a phosphate deficient diet to suppress FGF23 had endogenously increased Cyp27b1 mRNA, which was rescued in mice receiving HBEGF. In HEK293 cells with stable alpha-Klotho expression, FGF23 and HBEGF increased CYP24A1 mRNA expression. HBEGF, but not FGF23 bioactivity was blocked with EGF-receptor inhibition. Thus, our findings support that the paracrine/autocrine factor HBEGF could play novel roles in controlling genes downstream of FGF23 via targeting common signaling pathways.


Assuntos
Fatores de Crescimento de Fibroblastos , Vitamina D , Animais , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/genética , Células HEK293 , Humanos , Rim , Camundongos , Minerais , Fosfatos
12.
Biol Reprod ; 105(4): 918-933, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34086842

RESUMO

The efficiency of somatic cell nuclear transfer (scNT) for production of viable offspring is relatively low as compared to in vitro fertilization (IVF), presumably due to deficiencies in epigenetic reprogramming of the donor cell genome. Such defects may also involve the population of small non-coding RNAs (sncRNAs), which are important during early embryonic development. The objective of this study was to examine dynamic changes in relative abundance of sncRNAs during the maternal-to-embryonic transition (MET) in bovine embryos produced by scNT as compared to IVF by using RNA sequencing. When comparing populations of miRNA in scNT versus IVF embryos, only miR-2340, miR-345, and miR34a were differentially expressed in morulae, though many more miRNAs were differentially expressed when comparing across developmental stages. Also of interest, distinct populations of piwi-interacting like RNAs (pilRNAs) were identified in bovine embryos prior to and during embryonic genome activation (EGA) as compared bovine embryos post-EGA and differentiated cells. Overall, sncRNA sequencing analysis of preimplantation embryos revealed largely similar profiles of sncRNAs for IVF and scNT embryos at the 2-cell, 8-cell, morula, and blastocyst stages of development. However, these sncRNA profiles, including miRNA, piRNA, and tRNA fragments, were notably distinct prior to and after completion of the MET.


Assuntos
Bovinos/embriologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Pequeno RNA não Traduzido/metabolismo , Animais , Técnicas de Transferência Nuclear
13.
Biol Reprod ; 105(6): 1401-1415, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34514499

RESUMO

Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved.


Assuntos
Bovinos/embriologia , Embrião de Mamíferos/metabolismo , Fertilização in vitro/veterinária , Técnicas de Transferência Nuclear/veterinária , RNA Mensageiro/metabolismo , Pequeno RNA não Traduzido/metabolismo , Animais , Clonagem de Organismos/veterinária , Transcriptoma
14.
J Healthc Manag ; 66(1): 33-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33411484

RESUMO

EXECUTIVE SUMMARY: More than 600 Catholic hospitals operating in the United States face pressures for efficiency and effectiveness as well as compliance with demands of the Roman Catholic Church. They have responded to the pressures in various ways that have led to mixed models of organizational ownership and management. The purpose of this study was to describe and analyze the status of Catholic hospital ownership and management, especially the strategic and structural features of the parent health systems. Longitudinal data (2008-2017) were acquired and analyzed using repeated-measures analysis. Descriptive statistics were prepared using cross-sectional matched pairing for 2008 and 2017 data. Of 4,253 hospitals studied, 534 changed ownership or management. More Catholic Church-operated hospitals, regardless of type of ownership (for-profit, not-for-profit, church), became decentralized to a greater degree over the 8-year period and took on more attributes of non-Catholic hospitals.The 21st century Catholic hospital is more likely to be partnered with a non-Catholic hospital or to be owned by a for-profit system than to be solely partnered with or operated by another Catholic system. Today's Catholic hospitals appear to be more similar to their non-Catholic counterparts. With the trend toward larger systems that comprise more diverse partners, an increase in lay oversight could lead to further movement away from Catholic identity and the original mission of a hospital. As systems grow in size but shrink in number, administrators must make difficult decisions about the type and scope of services offered as well as the partners they need to deliver their services.


Assuntos
Catolicismo , Propriedade , Estudos Transversais , Hospitais , Hospitais Religiosos , Estados Unidos
15.
J Interprof Care ; 35(3): 343-351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32530333

RESUMO

Multiple models of interprofessional rounding (IPR) exist. However, researchers find mixed effects for the impact of IPR, pointing to the possibility that variations in design may influence the effectiveness of the practice. We explored whether IPR design variations (location, use of script, and role of the leader) are associated with team collaboration (partnership and cooperation) and team effectiveness as perceived by practitioners and patients (i.e., patient inclusion). A cross-sectional, survey-based method design was used targeting practitioners on 15 different hospital units at two academic health centers. Routinely collected Hospital Consumer Assessment of Healthcare Practitioners and Systems scores were used to capture patients' perceptions. Statistical methods included multilevel modeling with moderation analysis. There were several significant relationships among design, team collaboration, and team effectiveness. For the design, role of the leader and use of a script had a significant positive association with cooperation. Practitioners' perceptions of team effectiveness were associated with use of script, and cooperation moderated the relationships between practitioners' perceptions of team effectiveness and location, as well as the role of the leader. There was a significant inverse relationship between cooperation and patient inclusion. Results can inform organizations that are exploring, implementing, or improving IPR as well as considering alternative ways to evaluate their practices.


Assuntos
Relações Interprofissionais , Equipe de Assistência ao Paciente , Comportamento Cooperativo , Estudos Transversais , Atenção à Saúde , Humanos
16.
J Clin Nurs ; 29(7-8): 1141-1150, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31889345

RESUMO

AIMS AND OBJECTIVES: To explore practitioner perspectives on the facilitators, barriers and outcomes associated with interdisciplinary rounding practices (IDR). BACKGROUND: Interdisciplinary rounding practices is frequently used intervention to promote collaboration and patient-centred care in hospital units. Previous research supports that having IDR in place can lead to greater perceptions of collaboration and practitioner satisfaction; however, the practice does not always lead to better outcomes for patients. For IDR to be successful, unit leadership needs a greater understanding of facilitators and barriers as perceived by team members. At both the individual and organisational levels, there is limited understanding on what influences the success of IDR. This study seeks to explore factors influencing interdisciplinary rounding and perceived outcomes by team members. DESIGN: A quasi-qualitative design was used to address the aim of this study. Four open-ended questions were emailed to practitioners across fifteen units in two academic health centres. All units identified as having IDR in place. METHODS: A directed content analysis of practitioner responses was used to identify key themes. The Standards for Reporting Qualitative Research checklist was consulted for reporting of the results. RESULTS: A total of 141 practitioners responded to the open-ended questions. Three themes emerged from the data: (a) setting the stage; (b) the work of the team; and 3) benefits to patient care. CONCLUSIONS: The study provides a nuanced perspective of facilitators, barriers and potential outcomes associated with IDR. Future research is needed to gain additional perspective on the role the organisation plays in promoting a healthy workplace environment as well as providing patient-centred care. RELEVANCE TO CLINICAL PRACTICE: This study provides insight into facilitators and barriers to conducting interdisciplinary rounding practices in the inpatient setting. Results can be useful to unit leaders and staff that advocate for more collaborative and patient-centred rounding practices.


Assuntos
Comportamento Cooperativo , Equipe de Assistência ao Paciente/organização & administração , Assistência Centrada no Paciente/organização & administração , Adulto , Lista de Checagem , Feminino , Humanos , Relações Interprofissionais , Liderança , Masculino , Pesquisa Qualitativa
17.
Biol Reprod ; 100(2): 331-350, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165428

RESUMO

In mammals, small non-coding RNAs (sncRNAs) have been reported to be important during early embryo development. However, a comprehensive assessment of the inventory of sncRNAs during the maternal-to-zygotic transition (MZT) has not been performed in an animal model that better represents the sncRNA biogenesis pathway in human oocytes and embryos. The objective of this study was to examine dynamic changes in expression of sncRNAs during the MZT in bovine embryos produced by in vitro fertilization (IVF), which occurs at the 8-cell stage. An unbiased, discovery-based approach was employed using small RNAseq to profile sncRNAs in bovine oocytes, 8-cell stage embryos and blastocyst stage embryos followed by network and ontology analyses to explore the functional relevance of differentially expressed micro-RNAS (miRNAs). The relative abundance of miRNAs was markedly higher in 8-cell stage embryos compared to oocytes or blastocyst stage embryos. This shift in miRNA population was largely associated with upregulation of miRNAs predicted to target genes involved in the biological processes of cell development, cell division, Wnt signaling, and pluripotency, among others. Distinct populations of piwi-interacting-like RNAs (pilRNAs) were identified in bovine oocytes and blastocyst stage embryos, though pilRNAs were nearly absent in 8-cell stage embryos. Also, small nucleolar RNAs were highly expressed in 8-cell stage embryos. Overall, these data reveal a strong dynamic shift in the relative abundance of sncRNAs associated with the MZT in bovine oocytes and embryos, suggesting that these molecules may play important roles in the shift from maternal to zygotic control of gene expression.


Assuntos
Blastocisto/fisiologia , Bovinos/embriologia , Fertilização in vitro/veterinária , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Pequeno RNA não Traduzido/metabolismo , Animais , Sequência de Bases , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , MicroRNAs/genética , MicroRNAs/metabolismo , Oócitos/metabolismo , Pequeno RNA não Traduzido/genética
18.
PLoS Biol ; 14(4): e1002427, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27035636

RESUMO

X-linked hypophosphatemia (XLH) is the most frequent form of inherited rickets in humans caused by mutations in the phosphate-regulating gene with homologies to endopeptidases on the X-chromosome (PHEX). Hyp mice, a murine homologue of XLH, are characterized by hypophosphatemia, inappropriately low serum vitamin D levels, increased serum fibroblast growth factor-23 (Fgf23), and osteomalacia. Although Fgf23 is known to be responsible for hypophosphatemia and reduced vitamin D hormone levels in Hyp mice, its putative role as an auto-/paracrine osteomalacia-causing factor has not been explored. We recently reported that Fgf23 is a suppressor of tissue nonspecific alkaline phosphatase (Tnap) transcription via FGF receptor-3 (FGFR3) signaling, leading to inhibition of mineralization through accumulation of the TNAP substrate pyrophosphate. Here, we report that the pyrophosphate concentration is increased in Hyp bones, and that Tnap expression is decreased in Hyp-derived osteocyte-like cells but not in Hyp-derived osteoblasts ex vivo and in vitro. In situ mRNA expression profiling in bone cryosections revealed a ~70-fold up-regulation of Fgfr3 mRNA in osteocytes versus osteoblasts of Hyp mice. In addition, we show that blocking of increased Fgf23-FGFR3 signaling with anti-Fgf23 antibodies or an FGFR3 inhibitor partially restored the suppression of Tnap expression, phosphate production, and mineralization, and decreased pyrophosphate concentration in Hyp-derived osteocyte-like cells in vitro. In vivo, bone-specific deletion of Fgf23 in Hyp mice rescued the suppressed TNAP activity in osteocytes of Hyp mice. Moreover, treatment of wild-type osteoblasts or mice with recombinant FGF23 suppressed Tnap mRNA expression and increased pyrophosphate concentrations in the culture medium and in bone, respectively. In conclusion, we found that the cell autonomous increase in Fgf23 secretion in Hyp osteocytes drives the accumulation of pyrophosphate through auto-/paracrine suppression of TNAP. Hence, we have identified a novel mechanism contributing to the mineralization defect in Hyp mice.


Assuntos
Calcificação Fisiológica , Difosfatos/metabolismo , Raquitismo Hipofosfatêmico Familiar/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Osteócitos/metabolismo , Fosfatase Alcalina/genética , Animais , Osso e Ossos/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Camundongos , RNA Mensageiro/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Deficiência de Vitamina D/sangue
19.
Br J Clin Pharmacol ; 85(6): 1188-1198, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30207609

RESUMO

The most common heritable disorder of renal phosphate wasting, X-linked hypophosphataemia (XLH), was discovered to be caused by inactivating mutations in the phosphate regulating gene with homology to endopeptidases on the X-chromosome (PHEX) gene in 1995. Although the exact molecular mechanisms by which PHEX mutations cause disturbed phosphate handling in XLH remain unknown, focus for novel therapies has more recently been based upon the finding that the bone-produced phosphaturic hormone fibroblast growth factor-23 is elevated in XLH patient plasma. Previous treatment strategies for XLH were based upon phosphate repletion plus active vitamin D analogues, which are difficult to manage, fail to address the primary pathogenesis of the disease, and can have deleterious side effects. A novel therapy for XLH directly targeting fibroblast growth factor-23 via a humanized monoclonal antibody (burosumab-twza/CRYSVITA, henceforth referred to just as burosumab) has emerged as an effective, and recently approved, pharmacological treatment for both children and adults. This review will provide an overview of the clinical manifestations of XLH, the molecular pathophysiology, and summarize its current treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Biomarcadores/sangue , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/genética , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/imunologia , Predisposição Genética para Doença , Humanos , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Fenótipo , Resultado do Tratamento , Regulação para Cima
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