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1.
Lupus ; : 9612033241246642, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594605

RESUMO

BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

2.
Dev Cell ; 59(2): 211-227.e5, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38141609

RESUMO

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Transativadores , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angiogênese , Desenvolvimento Ósseo , Morfogênese , Osteoblastos/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
3.
Curr Oncol ; 30(12): 10224-10236, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38132378

RESUMO

The development and use of oral anticancer agents (OAAs) continue to grow, and supporting individuals on OAAs is now a priority as they find themselves taking these drugs at home with little professional guidance. This mapping review provides an overview of the current evidence concerning OAA-supportive adherence interventions, identifying potential gaps, and making recommendations to guide future work. Four large databases and the grey literature were searched for publications from 2010 to 2022. Quantitative, qualitative, mixed-method, theses/dissertations, reports, and abstracts were included, whereas protocols and reviews were excluded. Duplicates were removed, and the remaining publications were screened by title and abstract. Full-text publications were assessed and those meeting the inclusion criteria were retained. Data extracted included the year of publication, theoretical underpinnings, study design, targeted patients, sample size, intervention type, and primary outcome(s). 3175 publications were screened, with 435 fully read. Of these, 314 were excluded with 120 retained. Of the 120 publications, 39.2% (n = 47) were observational studies, 38.3% (n = 46) were quasi-experimental, and 16.7% (n = 20) were experimental. Only 17.5% (n = 21) were theory-based. Despite the known efficacy of multi-modal interventions, 63.7% (n = 76) contained one or two modalities, 33.3% (n = 40) included 3, and 3.3% (n = 4) contained four types of modalities. Medication adherence was measured primarily through self-report (n = 31) or chart review/pharmacy refills (n = 28). Given the importance of patient tailored interventions, future work should test whether having four intervention modalities (behavioral, educational, medical, and technological) guided by theory can optimize OAA-related outcomes.


Assuntos
Antineoplásicos , Adesão à Medicação , Humanos , Antineoplásicos/uso terapêutico
4.
J Pediatr ; 270: 113774, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37839510

RESUMO

OBJECTIVE: To determine if oral secretions (OS) can be used as a noninvasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. STUDY DESIGN: This was a retrospective, single center cohort study that included data and convenience samples from week-of-life (WoL) 3 from 2 independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatal Intensive Care Unit (NICU) (Cohort 1; n = 23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; n = 17 infants including 8 with BPD). RESULTS: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. CONCLUSIONS: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization and timely tailored treatment of at-risk infants with novel therapies.

5.
J Pers Med ; 13(5)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37241021

RESUMO

BACKGROUND: The PREVENTION e-platform was developed to provide accessible and evidence-based health information tailored to different Breast Cancer (BC) risk levels. The demonstration study objectives were to (1) assess the usability and perceived impact of PREVENTION on women with assigned hypothetical BC risk levels (i.e., near population, intermediate or high) and (2) explore perceptions and recommendations for e-platform improvement. METHODS: Thirty women with no history of cancer were recruited through social media, commercial centers, health clinics, and community settings in Montreal, Qc, Canada. Participants accessed e-platform content tailored to their assigned hypothetical BC risk level, and then completed study e-questionnaires including the user Mobile Application Rating Scale (uMARS), an e-platform quality scale (i.e., in terms of engagement, functionality, aesthetics, and information). A subsample (n = 18) was randomly selected for an individual follow-up semi-structured interview. RESULTS: The e-platform overall quality was high, with mean M = 4.01 (out of 5) and SD = 0.50. A total of 87% (n = 26) agreed or strongly agreed that PREVENTION increased their knowledge and awareness of BC risk, and 80% would recommend it to others while reporting likelihood of following lifestyle recommendations to decrease their BC risk. Follow up interviews indicated that participants perceived the e-platform as a trusted source of BC information and a promising means to connect with peers. They also reported that while the e-platform was easy to navigate, improvements were needed for connectivity, visuals, and the organization of scientific resources. CONCLUSION: Preliminary findings support PREVENTION as a promising means to provide personalized BC information and support. Efforts are underway to further refine the platform, assess its impact in larger samples and gather feedback from BC specialists.

6.
Curr Oncol ; 29(10): 7171-7180, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36290841

RESUMO

The SARS-CoV-2 (COVID-19) pandemic has accelerated the development and use of digital health platforms to support individuals with health-related challenges. This is even more frequent in the field of cancer care as the global burden of the disease continues to increase every year. However, optimal implementation of these platforms into the clinical setting requires careful planning and collaboration. An implementation project was launched between the Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Centre-Ouest-de-I'Île-de-Montreal and BELONG-Beating Cancer Together-a person-centred cancer navigation and support digital health platform. The goal of the project was to implement content and features specific to the CIUSSS, to be made available exclusively for individuals with cancer (and their caregivers) treated at the institution. Guided by Structural Model of Interprofessional Collaboration, we report on implementation processes involving diverse stakeholders including clinicians, hospital administrators, researchers and local community/patient representatives. Lessons learned include earlier identification of shared goals and clear expectations, more consistent reliance on virtual means to communicate among all involved, and patient/caregiver involvement in each step to ensure informed and shared decision making.


Assuntos
COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , Participação do Paciente , Cuidadores , Neoplasias/terapia
7.
Nat Commun ; 13(1): 4234, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918315

RESUMO

Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8+ T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Linfócitos T CD8-Positivos , Humanos , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Virais de Fusão
8.
Pancreas ; 51(5): 435-444, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881699

RESUMO

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT. METHODS: Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the "MStern" protocol. RESULTS: Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT. CONCLUSIONS: We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.


Assuntos
Transplante das Ilhotas Pancreáticas , Pancreatite Crônica , Feminino , Humanos , Transplante das Ilhotas Pancreáticas/métodos , Masculino , Pancreatectomia/métodos , Pancreatite Crônica/cirurgia , Proteômica , Transplante Autólogo , Resultado do Tratamento
9.
Hered Cancer Clin Pract ; 20(1): 8, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209930

RESUMO

BACKGROUND: Breast cancer risk stratification categorizes a woman's potential risk of developing the disease as near-population, intermediate, or high. In accordance, screening and follow up for breast cancer can readily be tailored following risk assessment. Recent efforts have focussed on developing more accessible means to convey this information to women. This study sought to document the relevance of an informational e-platform developed for these purposes. OBJECTIVE: To begin to assess a newly developed breast cancer risk stratification and decision support e-platform called PERSPECTIVE (PErsonalised Risk Stratification for Prevention and Early deteCTIon of breast cancer) among women who do not know their personal breast cancer risk (Phase 1). Changes (pre- and post- e-platform exposure) in knowledge of breast cancer risk and interest in undergoing genetic testing were assessed in addition to perceptions of platform usability and acceptability. METHODS: Using a pre-post design, women (N = 156) of differing literacy and education levels, aged 30 to 60, with no previous breast cancer diagnosis were recruited from the general population and completed self-report e-questionnaires. RESULTS: Mean e-platform viewing time was 18.67 min (SD 0.65) with the most frequently visited pages being breast cancer-related risk factors and risk assessment. Post-exposure, participants reported  significantly higher breast cancer-related knowledge (p < .001). Increases in knowledge relating to obesity, alcohol, breast density, menstruation, and the risk estimation process remained even when sociodemographic variables age and education were controlled. There were no significant changes in genetic testing interest post-exposure. Mean ratings for e-platform acceptability and usability were high: 26.19 out of 30 (SD 0.157) and 42.85 out of 50 (SD 0.267), respectively. CONCLUSIONS: An informative breast cancer risk stratification e-platform targeting healthy women in the general population can significantly increase knowledge as well as support decisions around breast cancer risk and assessment. Currently underway, Phase 2, called PERSPECTIVE, is seeking further content integration and broader implementation .

10.
Neonatology ; 119(2): 193-203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35073553

RESUMO

INTRODUCTION: Current techniques to diagnose and/or monitor critically ill neonates with bronchopulmonary dysplasia (BPD) require invasive sampling of body fluids, which is suboptimal in these frail neonates. We tested our hypothesis that it is feasible to use noninvasively collected urine samples for proteomics from extremely low gestational age newborns (ELGANs) at risk for BPD to confirm previously identified proteins and biomarkers associated with BPD. METHODS: We developed a robust high-throughput urine proteomics methodology that requires only 50 µL of urine. We utilized the methodology with a proof-of-concept study validating proteins previously identified in invasively collected sample types such as blood and/or tracheal aspirates on urine collected within 72 h of birth from ELGANs (gestational age [26 ± 1.2] weeks) who were admitted to a single Neonatal Intensive Care Unit (NICU), half of whom eventually developed BPD (n = 21), while the other half served as controls (n = 21). RESULTS: Our high-throughput urine proteomics approach clearly identified several BPD-associated changes in the urine proteome recapitulating expected blood proteome changes, and several urinary proteins predicted BPD risk. Interestingly, 16 of the identified urinary proteins are known targets of drugs approved by the Food and Drug Administration. CONCLUSION: In addition to validating numerous proteins, previously found in invasively collected blood, tracheal aspirate, and bronchoalveolar lavage, that have been implicated in BPD pathophysiology, urine proteomics also suggested novel potential therapeutic targets. Ease of access to urine could allow for sequential proteomic evaluations for longitudinal monitoring of disease progression and impact of therapeutic intervention in future studies.


Assuntos
Líquidos Corporais , Displasia Broncopulmonar , Biomarcadores , Líquidos Corporais/metabolismo , Displasia Broncopulmonar/complicações , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Proteoma , Proteômica
12.
Pancreas ; 50(1): 17-28, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33370019

RESUMO

OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influence the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection; after 1, 2, and 4 hours on ice; or after storage overnight at 4°C with or without RNase or protease inhibitors (PIs). Electrophoresis and mass spectrometry analysis determined protein abundance and quality, whereas nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding PIs delayed degradation. RNA was significantly degraded under all conditions compared with the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding PIs immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.


Assuntos
Ácidos Nucleicos/análise , Pancreatopatias/diagnóstico , Testes de Função Pancreática , Suco Pancreático/química , Proteínas/análise , Manejo de Espécimes , Biomarcadores/análise , Temperatura Baixa , Dano ao DNA , Endoscopia do Sistema Digestório , Congelamento , Humanos , Pancreatopatias/genética , Pancreatopatias/metabolismo , Valor Preditivo dos Testes , Inibidores de Proteases/farmacologia , Estabilidade Proteica , Proteólise , Estabilidade de RNA , Ribonucleases/antagonistas & inibidores , Ribonucleases/metabolismo , Secretina/administração & dosagem , Fatores de Tempo , Fluxo de Trabalho
13.
Can Oncol Nurs J ; 30(2): 103-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33118994

RESUMO

CONTEXTE: Le sentiment d'habilitation sur sa santé (health related empowerment) est un concept fondamental des soins centrés sur la personne. Toutefois, on en sait peu sur la manière dont ce concept s'articule chez les jeunes adultes ayant un diagnostic de cancer avancé. OBJECTIF: Explorer le sentiment d'habilitation à la lumière des expériences de soins de santé vécues par les jeunes adultes en phase de cancer avancé. CADRE ET PARTICIPANTS: Douze jeunes adultes (âgés de 21 à 39 ans) ont été recrutés dans un grand centre de cancérologie de Montréal, au Québec. MÉTHODOLOGIE: Des entretiens en profondeur durant entre 36 et 90 minutes ont été menés individuellement, enregistrés et retranscrits mot pour mot, puis analysés par thèmes. RÉSULTATS: Tout au long de l'expérience du cancer, les participants ont témoigné du désir soutenu de participer activement à leur traitement et à leurs soins. Quatre thèmes sont ressortis des données décrivant les processus d'attente, de prise en charge de la maladie, de mise en action et de recadrage. Sous-jacents à ces thèmes se trouvent les notions de conscience du corps, les obstacles à surmonter pour obtenir des soins, l'optimisation de la santé et la réflexion sur l'héritage qu'on laisse derrière soi. CONCLUSIONS: De façon générale, les participants voulaient demeurer en contrôle de la situation malgré les multiples difficultés inhérentes à un cancer de stade avancé. Si elles sont corroborées par d'autres recherches, ces conclusions pourraient orienter les approches de soins en oncologie afin qu'elles soient véritablement adaptées aux besoins des jeunes adultes.

14.
Can Oncol Nurs J ; 30(2): 93-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33118996

RESUMO

BACKGROUND: Health-related empowerment is a key concept in person-centred care. However, little is known of its core elements in young adults diagnosed with advanced cancer. OBJECTIVE: To explore empowerment in the context of young adults' healthcare experiences who are now in advanced stages of cancer. SETTING & PARTICIPANTS: Twelve young adults (aged 21 to 39 years) were recruited from a large cancer centre in Montreal, Quebec. METHODS: In-depth interviews lasting between 36 and 90 minutes were conducted individually, audio-recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Throughout the cancer trajectory, participants reported a sustained desire to be actively involved in their treatment and care. Four themes emerged from the data representing processes of waiting, managing, acting, and revisiting. Subsumed under these were notions of body ownership, facing obstacles to care, optimizing health, and (re)considering their legacy. CONCLUSIONS: Overall, participants wanted to remain in control of their situation despite the multiple challenges related to advanced cancer. If corroborated further, these findings should inform supportive cancer care approaches that are truly tailored to the needs of young adults.

15.
JCI Insight ; 4(15)2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391345

RESUMO

Wilms' tumor is the most common type of childhood kidney cancer. To improve risk stratification and identify novel therapeutic targets for patients with Wilms' tumor, we used high-resolution mass spectrometry proteomics to identify urine tumor markers associated with Wilms' tumor relapse. We determined the urine proteomes at diagnosis of 49 patients with Wilms' tumor, non-Wilms' tumor renal tumors, and age-matched controls, leading to the quantitation of 6520 urine proteins. Supervised analysis revealed specific urine markers of renal rhabdoid tumors, kidney clear cell sarcomas, renal cell carcinomas as well as those detected in patients with cured and relapsed Wilms' tumor. In particular, urine prohibitin was significantly elevated at diagnosis in patients with relapsed as compared with cured Wilms' tumor. In a validation cohort of 139 patients, a specific urine prohibitin ELISA demonstrated that prohibitin concentrations greater than 998 ng/mL at diagnosis were significantly associated with ultimate Wilms' tumor relapse. Immunohistochemical analysis revealed that prohibitin was highly expressed in primary Wilms' tumor specimens and associated with disease stage. Using functional genetic experiments, we found that prohibitin was required for the growth and survival of Wilms' tumor cells. Overexpression of prohibitin was sufficient to block intrinsic mitochondrial apoptosis and to cause resistance to diverse chemotherapy drugs, at least in part by dysregulating factors that control apoptotic cytochrome c release from mitochondrial cristae. Thus, urine prohibitin may improve therapy stratification, noninvasive monitoring of treatment response, and early disease detection. In addition, therapeutic targeting of chemotherapy resistance induced by prohibitin dysregulation may offer improved therapies for patients with Wilms' and other relapsed or refractory tumors.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias Renais/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Proteínas Repressoras/urina , Tumor de Wilms/diagnóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/antagonistas & inibidores , Estudos de Casos e Controles , Linhagem Celular Tumoral , Criança , Pré-Escolar , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Lactente , Rim/patologia , Rim/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Neoplasias Renais/urina , Masculino , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/urina , Nefrectomia , Proibitinas , Proteômica , Interferência de RNA , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Análise Serial de Tecidos , Tumor de Wilms/patologia , Tumor de Wilms/terapia , Tumor de Wilms/urina
16.
Cartilage ; 9(3): 313-320, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29156946

RESUMO

Objectives During arthroscopic or open joint surgery, articular cartilage may be subjected to mechanical insults by accident or design. These may lead to chondrocyte death, cartilage breakdown and posttraumatic osteoarthritis. We have shown that increasing osmolarity of routinely used normal saline protected chondrocytes against injuries that may occur during orthopedic surgery. Often several liters of irrigation fluid are used during an orthopedic procedure, which is usually kept at room temperature, but is sometimes chilled. Here, we compared the effect of normal and hyperosmolar saline solution at different temperatures on chondrocyte viability following cartilage injury using in vitro and in vivo models of scalpel-induced injury. Design Cartilage injury was induced in bovine osteochondral explants and the patellar groove of rats in vivo by a single pass of a scalpel blade in the presence of normal saline (300 mOsm) or hyperosmolar saline solution (600 mOsm, sucrose addition) at 4°C, 21°C, or 37°C. Chondrocytes were fluorescently labeled and visualized by confocal microscopy to assess cell death. Results Hyperosmolar saline reduced scalpel-induced chondrocyte death in both bovine and rat cartilage by ~50% at all temperatures studied (4°C, 21°C, 37°C; P < 0.05). Raising temperature of both irrigation solutions to 37°C reduced scalpel-induced cell death ( P < 0.05). Conclusions Increasing the osmolarity of normal saline and raising the temperature of the irrigation solutions to 37°C reduced chondrocyte death associated with scalpel-induced injury in both in vitro and in vivo cartilage injury models. A hyperosmolar saline irrigation solution at 37°C may protect cartilage by decreasing the risk of chondrocyte death during mechanical injury.


Assuntos
Doenças das Cartilagens/tratamento farmacológico , Cartilagem Articular/lesões , Cartilagem/lesões , Sobrevivência Celular/fisiologia , Condrócitos/efeitos dos fármacos , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Cartilagem Articular/efeitos dos fármacos , Bovinos , Morte Celular/efeitos dos fármacos , Condrócitos/ultraestrutura , Microscopia Confocal/instrumentação , Modelos Animais , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/normas , Concentração Osmolar , Substâncias Protetoras/farmacologia , Ratos , Solução Salina/farmacologia , Temperatura , Irrigação Terapêutica/efeitos adversos , Irrigação Terapêutica/métodos
17.
J Med Internet Res ; 19(11): e386, 2017 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-29127077

RESUMO

Connected health tools, including mobile phones, incorporate various functions that capture events, direct actions, and make informed decisions based on complex sources of data. Connected health, a term recently proposed by some academics and industry, refers to the development, testing, and integration of smart technology tools into health care. Through these means, connected health creates interconnectivity across various environments, profoundly changing the way we learn, self-regulate, and communicate with one another. In health care, mobile phones enable more precise diagnostics, personalized health recommendations that enhance patient experiences and outcomes while containing health care costs. However, for connected health to achieve its full potential, issues must be addressed pertaining to active engagement in use, privacy, security, and quality, as well as the development of evidence-based guidelines. This commentary discusses these key challenges and explores the promise of connected health, specifically eHealth and mHealth. Anchored within the context of cancer, the authors' area of expertise, the ideas put forward can readily be applied to other health-related disciplines.


Assuntos
Saúde da População , Telemedicina/métodos , Humanos
18.
Mol Cell Proteomics ; 14(10): 2814-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26223766

RESUMO

We describe a 96-well plate compatible membrane-based proteomic sample processing method, which enables the complete processing of 96 samples (or multiples thereof) within a single workday. This method uses a large-pore hydrophobic PVDF membrane that efficiently adsorbs proteins, resulting in fast liquid transfer through the membrane and significantly reduced sample processing times. Low liquid transfer speeds have prevented the useful 96-well plate implementation of FASP as a widely used membrane-based proteomic sample processing method. We validated our approach on whole-cell lysate and urine and cerebrospinal fluid as clinically relevant body fluids. Without compromising peptide and protein identification, our method uses a vacuum manifold and circumvents the need for digest desalting, making our processing method compatible with standard liquid handling robots. In summary, our new method maintains the strengths of FASP and simultaneously overcomes one of the major limitations of FASP without compromising protein identification and quantification.


Assuntos
Proteômica/instrumentação , Proteômica/métodos , Adsorção , Biomarcadores/urina , Feminino , Células HeLa , Humanos , Membranas Artificiais , Cistos Ovarianos/urina , Polivinil/química , Proteínas/análise , Proteínas/química , Manejo de Espécimes
19.
Mol Cell Proteomics ; 14(2): 430-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25473088

RESUMO

The function of a large percentage of proteins is modulated by post-translational modifications (PTMs). Currently, mass spectrometry (MS) is the only proteome-wide technology that can identify PTMs. Unfortunately, the inability to detect a PTM by MS is not proof that the modification is not present. The detectability of peptides varies significantly making MS potentially blind to a large fraction of peptides. Learning from published algorithms that generally focus on predicting the most detectable peptides we developed a tool that incorporates protein abundance into the peptide prediction algorithm with the aim to determine the detectability of every peptide within a protein. We tested our tool, "Peptide Prediction with Abundance" (PPA), on in-house acquired as well as published data sets from other groups acquired on different instrument platforms. Incorporation of protein abundance into the prediction allows us to assess not only the detectability of all peptides but also whether a peptide of interest is likely to become detectable upon enrichment. We validated the ability of our tool to predict changes in protein detectability with a dilution series of 31 purified proteins at several different concentrations. PPA predicted the concentration dependent peptide detectability in 78% of the cases correctly, demonstrating its utility for predicting the protein enrichment needed to observe a peptide of interest in targeted experiments. This is especially important in the analysis of PTMs. PPA is available as a web-based or executable package that can work with generally applicable defaults or retrained from a pilot MS data set.


Assuntos
Algoritmos , Espectrometria de Massas/métodos , Peptídeos/metabolismo , Sequência de Aminoácidos , Bases de Dados de Proteínas , Humanos , Dados de Sequência Molecular , Biblioteca de Peptídeos , Peptídeos/química , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/metabolismo
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