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1.
Nature ; 629(8013): 819-823, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38778232

RESUMO

Lanthanide rare-earth metals are ubiquitous in modern technologies1-5, but we know little about chemistry of the 61st element, promethium (Pm)6, a lanthanide that is highly radioactive and inaccessible. Despite its importance7,8, Pm has been conspicuously absent from the experimental studies of lanthanides, impeding our full comprehension of the so-called lanthanide contraction phenomenon: a fundamental aspect of the periodic table that is quoted in general chemistry textbooks. Here we demonstrate a stable chelation of the 147Pm radionuclide (half-life of 2.62 years) in aqueous solution by the newly synthesized organic diglycolamide ligand. The resulting homoleptic PmIII complex is studied using synchrotron X-ray absorption spectroscopy and quantum chemical calculations to establish the coordination structure and a bond distance of promethium. These fundamental insights allow a complete structural investigation of a full set of isostructural lanthanide complexes, ultimately capturing the lanthanide contraction in solution solely on the basis of experimental observations. Our results show accelerated shortening of bonds at the beginning of the lanthanide series, which can be correlated to the separation trends shown by diglycolamides9-11. The characterization of the radioactive PmIII complex in an aqueous environment deepens our understanding of intra-lanthanide behaviour12-15 and the chemistry and separation of the f-block elements16.

2.
Trauma Surg Acute Care Open ; 9(1): e001285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410756

RESUMO

Background: Stress ulcers in patients with traumatic brain injury (TBI) and spinal cord injury (SCI) present significant morbidity and mortality risks. Despite the low reported stress ulcer rates, stress ulcer prophylaxis (SUP) is widely administered in neurocritical care. It was hypothesized that universal SUP administration may not be associated with reduced rates of complications across all neurocritical care patients. Methods: This retrospective study encompassed neurocritical care patients aged ≥18 with moderate or severe TBI or SCI, admitted to the intensive care unit (ICU) between October 2020 and September 2021, across six level I trauma centers. Exclusions included patients with an ICU stay <2 days, prior SUP medication use, and pre-existing SUP diagnoses. The primary exposure was SUP, with the primary outcome being clinically significant gastrointestinal bleeds (CSGIBs). Secondary outcomes included pneumonia and in-hospital mortality. Patients were stratified by admission Glasgow Coma Scale (GCS) groups. Results: Among 407 patients, 83% received SUP, primarily H2 receptor antagonists (88%) and proton pump inhibitors (12%). Patients on SUP were significantly younger, had lower admission GCS scores, higher Injury Severity Scores, longer ICU stays, and higher rates of mechanical ventilation than non-SUP patients. Overall, CSGIBs were rare (1%) and not significantly different between the SUP and non-SUP groups (p=0.06). However, CSGIBs exclusively occurred in patients with GCS scores of 3-8, and SUP was associated with a significantly lower rate of CSGIBs in this subgroup (p=0.03). SUP was also linked to significantly higher pneumonia rates in both GCS 3-8 and GCS 9-12 patients. Conclusions: This study highlights the low incidence of CSGIBs in neurocritical trauma patients and suggests potential benefits of SUP, particularly for those with severe neurological impairment. Nevertheless, the increased risk of pneumonia associated with SUP in these patients warrants caution. Further research is crucial to refine SUP guidelines for neurocritical care patients and inform optimal strategies. Level of evidence: Level III, retrospective.

3.
Tissue Eng Part A ; 30(7-8): 357-366, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38318848

RESUMO

Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation. Bilateral defects were created by SD on the femoral medial condyle of female New Zealand white rabbits (n = 12), and the left joint received cLIUS treatment (3.8 MHz, 3.5 Vpp, 8 min/application/day) and the contralateral right joint served as the control. On day 7 postsurgery, synovial fluid was aspirated, and the cytokine levels were assessed by Quantibody™ assay. Rabbits were euthanized at 8 weeks and outcomes were assessed macroscopically and histologically. Defect areas in the right joints exhibited boundaries, incomplete fill, irregular cartilage surfaces, loss of glycosaminoglycan (GAG), and absence of chondrocytes. In contrast, the repaired defect area in the joints that received cLIUS showed complete fill, positive staining for GAG with rounded chondrocyte morphology, COL2A1 staining, and columnar organization. Synovial fluid collected from cLIUS-treated left knee joints had lower levels of IL1, TNFα, and IFNγ when compared to untreated right knee joints, alluding to the potential of cLIUS to mitigate early inflammation. Further at 8 weeks, left knee joints (n = 12) consistently scored higher on the O'Driscoll scale, with a higher percent hyaline cartilage score. No adverse impact on bone or change in the joint space was noted. Upon a single exposure of cLIUS to TNFα-treated cells, nuclear localization of pNFκB and SOX9 was visualized by double immunofluorescence and the expression of markers associated with the NFκB pathway was assayed by quantitative real-time polymerase chain reaction. cLIUS extends its chondroprotective effects by titrating pNFκB levels, preventing its nuclear translocation, while maintaining the expression of SOX9, the collagen II transcription factor. Our combined results demonstrate that healing of chondral defects treated with marrow stimulation by SD can be accelerated by employing cLIUS regimen that possesses chondroinductive and chondroprotective properties. Impact statement Repair of cartilage represents an unsolved biomedical burden. In vitro, continuous low-intensity ultrasound (cLIUS) has been demonstrated to possess chondroinductive and chondroprotective potential. To our best knowledge, the use of cLIUS to improve cartilage repair outcomes upon marrow stimulation, in vivo, has not been reported and our work reported here fills that gap. Our results demonstrated enhanced cartilage repair outcomes under cLIUS (3.8 MHz) in a rabbit model of subchondral injury by subchondral drilling. Enhanced repair stemmed from mesenchymal stem cell differentiation in vivo and the subsequent synthesis of articular cartilage-specific matrix.


Assuntos
Cartilagem Articular , Fator de Necrose Tumoral alfa , Coelhos , Feminino , Animais , Ultrassonografia , Colágeno/metabolismo , Regulação da Expressão Gênica , Glicosaminoglicanos/metabolismo
5.
Leukemia ; 37(9): 1782-1791, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37543655

RESUMO

Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1-18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P > 0.999), anti-pegaspargase antibodies (P = 0.327), or pancreatitis (P = 0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P < 0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.


Assuntos
Antineoplásicos , Pancreatite , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Humanos , Rituximab/uso terapêutico , Asparaginase/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Polietilenoglicóis , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antineoplásicos/uso terapêutico
6.
PLoS One ; 17(11): e0251470, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36327273

RESUMO

IMPORTANCE: The rapid proliferation of COVID-19 has left governments scrambling, and several data aggregators are now assisting in the reporting of county cases and deaths. The different variables affecting reporting (e.g., time delays in reporting) necessitates a well-documented reliability study examining the data methods and discussion of possible causes of differences between aggregators. OBJECTIVE: To statistically evaluate the reliability of COVID-19 data across aggregators using case fatality rate (CFR) estimates and reliability statistics. DESIGN, SETTING, AND PARTICIPANTS: Cases and deaths were collected daily by volunteers via state and local health departments, as primary sources and newspaper reports, as secondary sources. In an effort to begin comparison for reliability statistical analysis, BroadStreet collected data from other COVID-19 aggregator sources, including USAFacts, Johns Hopkins University, New York Times, The COVID Tracking Project. MAIN OUTCOMES AND MEASURES: COVID-19 cases and death counts at the county and state levels. RESULTS: Lower levels of inter-rater agreement were observed across aggregators associated with the number of deaths, which manifested itself in state level Bayesian estimates of COVID-19 fatality rates. CONCLUSIONS AND RELEVANCE: A national, publicly available data set is needed for current and future disease outbreaks and improved reliability in reporting.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Teorema de Bayes , Reprodutibilidade dos Testes , Surtos de Doenças , New York
7.
Eur Urol Focus ; 8(6): 1751-1757, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35534391

RESUMO

BACKGROUND: Gender disparities in editorial board composition exist across a variety of surgical subspecialties. OBJECTIVE: To investigate temporal variation in gender representation on the editorial boards of urology journals and assess the relationship between editorial board composition and female authorship. DESIGN, SETTING, AND PARTICIPANTS: We analyzed female authorship and editorial board composition between 2002 and 2020 among eight high-impact urology journals. Female publication status was assessed using publication records retrieved from PubMed. Editorial board information was manually extracted and titles were grouped for comparison as Editor-in-Chief, mid-level editor, and consulting editors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Female representation across different editorial levels was analyzed via hierarchical logistic regression with additional terms to test for between-journal differences in overall representation and change over time. The relationship between representation on editorial boards and as publication authors was assessed at the journal level via correlation. RESULTS AND LIMITATIONS: Eight journals and 49 412 articles were analyzed. No female has held the title of Editor-in-Chief for any of these eight journals in 18 yr. Significant growth was seen for mid-level editors, whereas no growth was seen for consulting editors. Neurourology and Urodynamics and Journal of Sexual Medicine had significantly higher than average female editorial board representation (p < 0.05). Across the eight journals, there was a statistically significant correlation between the proportion of overall female authors and female editors (r = 0.93, 95% confidence interval 0.65-0.99). For all journals, the proportion of female contributing authors is greater than the proportion of female editorial board members. CONCLUSIONS: Women in urology represent a small but increasing presence as editorial board members. Clear differences exist between journals, potentially attributable to specialty-specific demographics. Despite increasing representation, no female has ever been appointed Editor-in-Chief for any of the eight journals evaluated. At the journal-specific level, a positive correlation was observed between female editorial staff and female authorship. Given the implication of both academic authorship and editorial board assignment on academic advancement, actionable changes are outlined to guide improvement in gender diversity at the journal level. PATIENT SUMMARY: Females are under-represented on the editorial boards for urology journals, although some roles have seen growth over time. Moreover, female editorial board membership is associated with representation of females among article authors. Gender disparities in both are noteworthy because they affect career paths and contribute to the gender gap in urology.


Assuntos
Feminino , Humanos
8.
Sex Med Rev ; 10(2): 231-239, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34992003

RESUMO

INTRODUCTION: A clear and well-documented gender bias exists in the evaluation of sexual outcomes for women undergoing urologic surgery. Due to the anatomic template of anterior exenteration, women are commonly left with side effects that include sexual dysfunction and the perpetuated effects of surgical menopause. OBJECTIVES: To present evaluation and treatment recommendations for female sexual dysfunction treatment and evaluation, in addition to surgical templates during radical cystectomy (RC). METHODS: This article reviews current literature regarding sexual function and RC with urinary diversion in female bladder cancer patients. Furthermore, this review will provide a review of techniques for organ and neurovascular preservation, along with novel vaginal reconstruction templates. Our review will further focus on emerging technology, including minimally invasive surgery and organ and nerve preservation, directed at preservation of female sexual function. RESULTS: Clinically, studies have demonstrated that females who have undergone genitalia-sparing and neurovascular preservation during RC regained sexual activity earlier than patients undergoing traditional RC. If organ and nerve preservation is not feasible due to involvement of trigone or bladder neck, vaginal reconstruction can mitigate the sexual dysfunction that results from a loss of the anterior vagina during a standard RC. CONCLUSION: Female sexual dysfunction is associated with high levels of patient distress and is best comanaged with a multidisciplinary treatment approach, including preoperative counseling, intraoperative nerve, and organ preservation, and postoperative interventions to mitigate sexual side effects. Davis L, Isali I, Prunty M, et al. Female Sexual Function Following Radical Cystectomy in Bladder Cancer. Sex Med Rev 2022;10:231-239.


Assuntos
Disfunções Sexuais Fisiológicas , Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia/efeitos adversos , Feminino , Humanos , Masculino , Sexismo , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/cirurgia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos
9.
Urology ; 165: 98-105, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34813833

RESUMO

OBJECTIVE: To characterize the epidemiological profile of metastatic bladder cancer (BC) and assess mortality rate with respect to race and gender across the three most common histologies of bladder cancer-Transitional Cell Carcinoma, Adenocarcinoma, and SCC (Squamous Cell Carcinoma). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results Program database (2000-2017) was queried for all metastatic bladder cancer patients at presentation. Our primary exposure consists of four race/gender combinations. One-way ANOVA and Chi-square tests compared categorical and continuous variables across the exposure variable, respectively. Univariable and multivariable Cox proportional hazards regression analyses were used to examine the association between race/gender combinations and the overall and cancer specific survival adjusting for the other variables. RESULTS: A total of 312,846 bladder cancer patients, 6337 with distant metastases and 11,446 with regional metastases were evaluated. Black female cancer specific survival in metastatic disease was disproportionally lower compared to all race/gender for Transitional Cell Carcinoma 4.3% (95% CI: 1.6-8.9), SCC 2.6% (95% CI: 0.2-11.8), and Adenocarcinoma 6.4% (0.4%-25%). In regional metastastatic disease, worse cancer specific mortality was associated with identifying as a Black Female (aHR 1.17, P = .023), SCC (aHR 1.8, P <.001), increasing age (aHR 1.3, P <.001), and poorly differentiated grade (aHR 2.01, P <.001). CONCLUSION: Black females experience excess mortality in overall and cancer oncologic outcomes in metastatic BC. Our findings contribute to the body of research warranting examination of the impact of social determinants of health and provider decisions on BC survivorship and contribute to physician decision making in the treatment and surveillance of bladder cancer.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/patologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Estadiamento de Neoplasias , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
10.
Soc Sci Med ; 284: 114216, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34274707

RESUMO

BACKGROUND: Tasmania, Australia has a small widely dispersed regional and rural population. The Conception to Community (C2C) Study Database was established as a research platform to inform service planning and policy development and improve health outcomes for Tasmanian mothers and children. The aims of this study were to establish by maternal socio-demographic characteristics: 1) the distribution of births in Tasmania; 2) hospital utilisation for children from birth to 5-years; and 3) the association between child and maternal emergency department (ED) presentation rates. METHODS: Perinatal and public hospital ED and admitted patient data were linked for every child born in Tasmania between 2008-09 to 2013-14, and their mothers. Individualised rates of ED presentations and hospital admissions were calculated from birth to 5-years. Frequent presenters to ED were defined as having at least four presentations per annum. Ratios of ED presentation and hospital admission rates by sociodemographic characteristics (region (north, north-west, south), rurality, maternal age, and area socioeconomic disadvantage) were estimated using mixed-effects negative binomial models, with random intercepts for each child and family. RESULTS: The C2C Database is comprised of records for 37,041 children and 27,532 mothers. One-in-ten Tasmanian babies lived in a remote area. The mean yearly rate of ED presentations per child varied by sex, age, region and rurality. Frequent presenters were more likely to reside in the north-west or north, in urban areas, have mothers under 20- years, be male, and live in more disadvantaged areas, with 2.3% of children frequent presenters in their first year of life. The odds of a child being a frequent presenter during their first-year was 6.1- times higher if the mother was a frequent presenter during this period. CONCLUSION: Associations between maternal and child health service use and combined effects of regionality and rurality highlight opportunities for targeted intervention and service innovations.


Assuntos
Serviço Hospitalar de Emergência , População Rural , Austrália , Criança , Feminino , Hospitalização , Humanos , Lactente , Masculino , Modelos Estatísticos , Gravidez
11.
Am J Transplant ; 21(4): 1465-1476, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33021057

RESUMO

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor ß chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFß) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.


Assuntos
Transplante de Coração , Aloenxertos , Vasos Coronários , Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , Humanos , Linfócitos T
12.
Am J Obstet Gynecol ; 223(2): 219-220.e1, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32405073

RESUMO

The coronavirus disease 2019 pandemic has redefined "essential care," and reproductive healthcare has become a frequently targeted and debated topic. As obstetricians and gynecologists, we stand with our patients and others as advocates for women's reproductive health. With the medical and surgical training to provide all aspects of reproductive healthcare, obstetricians and gynecologists are indispensable and uniquely positioned to advocate for the full spectrum of care that our patients need right now. All patients have a right to these services. Contraception and abortion care remain essential, and we need to work at the local, state, and federal levels on policies that preserve these critical services. We must also support policies that will promote expansion of care, including lengthening Medicaid pregnancy and postpartum coverage. Although we continue to see patients, this is the time to engage outside clinical encounters by participating in lobbying and other advocacy efforts to preserve essential services, protecting the health, life, and welfare of our patients during the coronavirus disease 2019 pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Aborto Induzido , Assistência Ambulatorial , COVID-19 , Anticoncepção , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Saúde Reprodutiva , SARS-CoV-2 , Saúde da Mulher
13.
J Cell Biol ; 219(3)2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32211893

RESUMO

The polyphosphoinositides (PPIn) are central regulatory lipids that direct membrane function in eukaryotic cells. Understanding how their synthesis is regulated is crucial to revealing these lipids' role in health and disease. PPIn are derived from the major structural lipid, phosphatidylinositol (PI). However, although the distribution of most PPIn has been characterized, the subcellular localization of PI available for PPIn synthesis is not known. Here, we used several orthogonal approaches to map the subcellular distribution of PI, including localizing exogenous fluorescent PI, as well as detecting lipid conversion products of endogenous PI after acute chemogenetic activation of PI-specific phospholipase and 4-kinase. We report that PI is broadly distributed throughout intracellular membrane compartments. However, there is a surprising lack of PI in the plasma membrane compared with the PPIn. These experiments implicate regulation of PI supply to the plasma membrane, as opposed to regulation of PPIn-kinases, as crucial to the control of PPIn synthesis and function at the PM.


Assuntos
Membrana Celular/metabolismo , Membranas Intracelulares/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilinositóis/metabolismo , Animais , Células COS , Chlorocebus aethiops , Diglicerídeos/metabolismo , Cinética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia Confocal , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
14.
Int J Rheum Dis ; 22(12): 2213-2217, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31709741

RESUMO

A 36-year-old man was treated for several years with multiple agents for ankylosing spondylitis based on positive human leukocyte antigen-B27 and sacroiliitis. He was also diagnosed with osteoporosis and hypophosphatemia. Over these years, from being an avid runner, he became dependent on a walker for ambulation. The lack of treatment response and the low phosphorus were clues that eventually led to a diagnosis of tumor-induced osteomalacia. This case discusses the importance of not solely relying on genetic markers and sacroiliitis for diagnosing ankylosing spondylitis as other conditions can cause similar presentations.


Assuntos
Neoplasias Femorais/diagnóstico , Antígeno HLA-B27/genética , Osteomalacia/diagnóstico , Sacroileíte/diagnóstico , Espondilartrite/diagnóstico , Adulto , Diagnóstico Diferencial , Neoplasias Femorais/complicações , Neoplasias Femorais/cirurgia , Antígeno HLA-B27/imunologia , Humanos , Masculino , Osteomalacia/etiologia , Osteomalacia/genética , Osteomalacia/imunologia , Osteotomia , Valor Preditivo dos Testes , Sacroileíte/etiologia , Sacroileíte/genética , Sacroileíte/imunologia , Espondilartrite/genética , Espondilartrite/imunologia , Resultado do Tratamento
15.
Tissue Eng Part A ; 25(21-22): 1538-1549, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31190618

RESUMO

Failure of the host/graft interface to integrate impedes the success of cartilage repair protocols. Continuous low-intensity ultrasound (cLIUS) at the resonant frequency of 5 MHz is proposed as a treatment modality for promoting native-to-native cartilage integration in vitro. Cylindrical incisions (4 mm) simulating chondral discontinuity were made in bovine cartilage and osteochondral explants, and maintained under cLIUS stimulation (14 kPa [5 MHz, 2.5 Vpp], 20 min, four times/day) for 28 days. Incised cartilage and osteochondral explants were categorized into three study groups; Group I: cLIUS was applied immediately upon incision; Group II: cLIUS was applied after 14 days following incision; Group-III: after 14 days following incision, explants were treated with 0.1% hyaluronidase and 30 U/mL collagenase VII. As a separate study group, incised osteochondral explants were treated immediately with cLIUS at a nonresonant frequency of 2 MHz (14 kPa [2 MHz, 6 Vpp], 20 min, four times/day). Cellular migration was analyzed by scratch assays, and by visualizing migrating cells into the hydrogel core of cartilage/hydrogel constructs. Explants under cLIUS (5 MHz) displayed higher percent apposition along with gap closures when compared with untreated controls and explants treated with cLIUS at 2 MHz. cLIUS (5 MHz)-treated explants were immunopositive for type II collagen. The strength of native-to-native cartilage integration was higher (p = 0.005) in cLIUS-treated cartilage explants at 0.19 ± 0.08 MPa as compared with 0.05 ± 0.03 MPa in untreated controls. Enhanced cartilage phenotype coupled with increased cellular migration were noted under cLIUS (5 MHz), alluding to the observed integration between cartilage interfaces. Collectively, cLIUS at cell resonant frequency promoted integrative cartilage repair, therefore, has the potential to improve cartilage repair outcomes. Impact Statement Lack of integration between the host and graft cartilage interfaces impedes the success of cartilage repair techniques. Continuous low-intensity ultrasound (cLIUS) is documented to induce chondrogenesis and chondrocyte phenotype. However, integrative cartilage repair under cLIUS has not been evaluated. Our results demonstrated integration between cartilage interfaces, increased percent apposition, increased strength of integration, and maintenance of cartilage phenotype under cLIUS (5 MHz). Integrative repair under cLIUS (5 MHz) stemmed from enhanced migration of cells and increased expression of cartilage-specific genes, namely SOX9 and COL2A1. Thus, cLIUS has the potential to improve the outcomes of grafting protocols for cartilage repair.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Ultrassonografia , Animais , Cartilagem Articular/metabolismo , Bovinos , Movimento Celular , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Regulação da Expressão Gênica , Humanos , Modelos Biológicos
16.
Am J Case Rep ; 20: 659-663, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064976

RESUMO

BACKGROUND Fibromyalgia (FM) is a common disorder of diffuse musculoskeletal pain. It is distinctly different from polymyalgia rheumatica (PMR), a disease seen in people over the age of 50 years. Hallmark features of PMR are the presence of elevated erythrocytes sedimentation rate (ESR) and/or C-reactive protein (CRP). These markers are normal in FM. Obesity in itself can be associated with elevated CRP and ESR, and when obese patients present with myalgia and elevated inflammatory markers, diagnostic confusion can ensue. CASE REPORT We describe a case of 38-year-old female with diffuse musculoskeletal pain and elevated ESR and CRP who was initially misdiagnosed with PMR and responded partially to steroids. She developed severe adverse effects from chronic steroid use. She was ultimately diagnosed with FM. CONCLUSIONS We highlight features to help clinicians avoid the pitfall of diagnosing PMR in young obese patients with FM and elevated inflammatory markers. In this case report, we discuss the features of FM, PMR, PMR-like symptoms presentation, and the association of obesity with elevated inflammatory markers.


Assuntos
Sedimentação Sanguínea , Proteína C-Reativa/análise , Fibromialgia/diagnóstico , Mialgia/etiologia , Obesidade/complicações , Adulto , Biomarcadores/sangue , Erros de Diagnóstico , Feminino , Fibromialgia/sangue , Humanos , Mialgia/complicações , Polimialgia Reumática/sangue , Polimialgia Reumática/diagnóstico
17.
BMC Womens Health ; 19(1): 62, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064368

RESUMO

BACKGROUND: Pain impacts upon psychological wellbeing. In pregnant and postpartum women psychological distress may negatively affect the mother-infant relationship and lead to adverse infant development. Yet, co-occurrence of pain with psychological distress in women of reproductive age has not been investigated. Therefore, this study aimed to: 1) assess prevalence of psychological distress in reproductive aged women by pain severity; and 2) examine the self-rated health status of reproductive aged women with and without pain. METHOD: Data for women aged 18-49 years were obtained from the 2011-12 Australian Bureau of Statistics National Health Survey. Sample data were weighted to give population estimates. Recent pain severity, self-rated health and psychological distress were analysed for pregnant, breastfeeding and non-pregnant/non-breastfeeding women. RESULTS: Moderate-to-very severe pain was reported by 17.6% of pregnant (sample n = 165, weighted N = 191,856), 25.9% of breastfeeding (sample n = 210, weighted N = 234,601) and 23.9% of non-pregnant/non-breastfeeding women (sample n = 4005, weighted N = 4,607,140). Psychological distress was associated with pain in non-pregnant/non-breastfeeding women (p < 0.001). High-to-very high distress was seen in 26.4% (95% CI, 23.2-29.6) of NP/NBF, 8.1% (95% CI, 0-17.2) of breastfeeding and 7.3% (95% CI, 0-18.0) of pregnant women with moderate-to-very severe pain. Self-rated health status was associated with pain severity in pregnant (p = 0.001) and non-pregnant/non-breastfeeding (p < 0.001) women. CONCLUSION: Given the strong association between psychological distress and pain in non-pregnant/non-breastfeeding women, and the relatively common occurrence of moderate-to-very severe pain in both pregnant and breastfeeding women, assessment of psychological distress levels in all women of reproductive age who report experiencing moderate-to-very severe levels of pain may be of benefit.


Assuntos
Nível de Saúde , Dor/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Austrália/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Dor/epidemiologia , Medição da Dor , Adulto Jovem
18.
Women Birth ; 32(2): e272-e278, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31007208

RESUMO

BACKGROUND: The increasing prevalence and adverse outcomes associated with opioid analgesia use in women of reproductive age have become a significant public health issue internationally, with use during pregnancy potentially affecting maternal and infant health outcomes. OBJECTIVE: This study aims to provide national estimates of chronic pain, pain severity and analgesia use in Australian women of reproductive age by pregnancy status. METHOD: Data were obtained from the Australian Bureau of Statistics 2011-12 National Health Survey (n=20,426). Weighting was applied to sample data to obtain population estimates. For this study data were analysed for pregnant (n=166, N=192,617) and non-pregnant women (n=4710, N=5,256,154) of reproductive age (15-49 years). RESULTS: Chronic or reoccurring pain was reported in 5.1% of pregnant women and 9.7% of non-pregnant women, and 0.7% and 2.6% of pregnant and non-pregnant women reported recent opioid analgesia use respectively. Moderate-to-very severe pain was more common in pregnant than non-pregnant women taking opioid analgesics, and no pain and very mild-to-mild pain in non-pregnant women. CONCLUSION: Approximately 1 in 20 pregnant Australian women have chronic or reoccurring pain. Opioid analgesia was used by around 1% of Australian pregnant women during a two-week period, with use associated with moderate-to-very severe pain. Given that the safety of many analgesic medications in pregnancy remains unknown, pregnant women and health professionals require accurate, up-to-date information on the risks and benefits of analgesic use during pregnancy. Further evidence on the decision-making processes of pregnant women with pain should assist health professionals maximise outcomes for mothers and infants.


Assuntos
Analgesia/estatística & dados numéricos , Analgésicos Opioides/uso terapêutico , Dor Crônica/epidemiologia , Complicações na Gravidez/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Austrália/epidemiologia , Dor Crônica/tratamento farmacológico , Dor Crônica/patologia , Feminino , Humanos , Medição da Dor , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/patologia , Prevalência , Adulto Jovem
19.
BMJ Case Rep ; 20182018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-30002215

RESUMO

Felty syndrome(FS) is an uncommon, but severe, extra-articular manifestation of rheumatoid arthritis (RA). It occurs in patients with longstanding RA. It is extremely rare for RA to present as FS or develop after initially presenting as neutropaenia and splenomegaly. We describe a case of 47-year-old woman who was diagnosed simultaneously with FS and possible RA after testing positive for anticyclic citrullinated peptide antibody, but a negative rheumatoid factor. She had an excellent response to methotrexate. We review the existing literature of such cases and emphasise the importance of serological testing for RA in patients presenting with neutropaenia and splenomegaly, even in the absence of joint symptoms or prior diagnosis of RA.


Assuntos
Artrite Reumatoide/diagnóstico , Síndrome de Felty/diagnóstico , Neutropenia/diagnóstico , Esplenomegalia/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Diagnóstico Diferencial , Síndrome de Felty/etiologia , Síndrome de Felty/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Esplenomegalia/imunologia
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