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1.
J Clin Nurs ; 32(17-18): 6165-6178, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37154497

RESUMO

AIM: To understand the issues surrounding collaborative practice and collaboration experiences among general ward staff in the escalation of care for clinically deteriorating patients. DESIGN: A systematic synthesis without meta-analysis. REVIEW METHODS: Seven electronic databases (CINAHL, Cochrane, Embase, PsycINFO, PubMed, Scopus and ProQuest Theses and Dissertations) were searched from their inception to 30 April 2022. Two reviewers independently screened titles, abstracts and full text for eligibility. The critical appraisal skill programme, Joanna Briggs Institute checklist for analytical cross-sectional studies and mixed methods appraisal tool were used to appraise the quality of the included studies. Both quantitative and qualitative research data were extracted, analysed and then synthesised using the data-based convergent qualitative synthesis approach. This review adhered to the Synthesis without meta-analysis (SWiM) reporting guidelines. RESULTS: A total of 17 studies were included. Two themes and six sub-themes were generated: (1) intraprofessional factors-inadequate handover, workload and mutual support, raising and acting on concerns, and seeking help from seniors and (2) interprofessional factors-differences in communication styles, and hierarchical approach versus interpersonal relationships. CONCLUSIONS: This systematic review highlights the need to address the intra- and interprofessional issues surrounding collaborative practice in escalation of care among general ward staff. IMPLICATIONS FOR THE PROFESSION: Findings from this review will inform healthcare leaders and educators on the development of relevant strategies and multi-disciplinary training to foster effective teamwork among nurses and doctors, with the goal of improving the escalation of care for patients with clinical deterioration. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.


Assuntos
Deterioração Clínica , Quartos de Pacientes , Humanos , Estudos Transversais , Atenção à Saúde , Relações Interpessoais , Pesquisa Qualitativa
2.
J Cell Sci ; 127(Pt 19): 4186-200, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25107365

RESUMO

Focal adhesions (FAs) undergo maturation that culminates in size and composition changes that modulate adhesion, cytoskeleton remodeling and differentiation. Although it is well recognized that stimuli for osteogenesis of mesenchymal stem cells (MSCs) drive FA maturation, actin organization and stress fiber polarization, the extent to which FA-mediated signals regulated by the FA protein composition specifies MSC commitment remains largely unknown. Here, we demonstrate that, upon dexamethasone (osteogenic induction) treatment, guanine nucleotide exchange factor H1 (GEF-H1, also known as Rho guanine nucleotide exchange factor 2, encoded by ARHGEF2) is significantly enriched in FAs. Perturbation of GEF-H1 inhibits FA formation, anisotropic stress fiber orientation and MSC osteogenesis in an actomyosin-contractility-independent manner. To determine the role of GEF-H1 in MSC osteogenesis, we explore the GEF-H1-modulated FA proteome that reveals non-muscle myosin-II heavy chain-B (NMIIB, also known as myosin-10, encoded by MYH10) as a target of GEF-H1 in FAs. Inhibition of targeting NMIIB into FAs suppresses FA formation, stress fiber polarization, cell stiffness and osteogenic commitments in MSCs. Our data demonstrate a role for FA signaling in specifying MSC commitment.


Assuntos
Adesões Focais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Diferenciação Celular/fisiologia , Linhagem da Célula , Humanos , Osteogênese , Transdução de Sinais
3.
J Cell Mol Med ; 19(5): 934-47, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25683605

RESUMO

Cancer metastasis occurs via a progress involving abnormal cell migration. Cell migration, a dynamic physical process, is controlled by the cytoskeletal system, which includes the dynamics of actin organization and cellular adhesive organelles, focal adhesions (FAs). However, it is not known whether the organization of actin cytoskeletal system has a regulatory role in the physiologically relevant aspects of cancer metastasis. In the present studies, it was found that lung adenocarcinoma cells isolated from the secondary lung cancer of the lymph nodes, H1299 cells, show specific dynamics in terms of the actin cytoskeleton and FAs. This results in a higher level of mobility and this is regulated by an immature FA component, ß-PIX (PAK-interacting exchange factor-ß). In H1299 cells, ß-PIX's activity was found not to be down-regulated by sequestration onto stress fibres, as the cells did not bundle actin filaments into stress fibres. Thus, ß-PIX mainly remained localized at FAs, which allowed maturation of nascent adhesions into focal complexes; this resulted in actin polymerization, increased actin network integrity, changes in the intracellular microrheology at the peripheral of the cell, and cell polarity, which in turn regulated cell migration. Perturbation of ß-PIX caused an inhibition of cell migration, including migration velocity, accumulated distance and directional persistence. Our results demonstrate the importance of ß-PIX to the regulation of high mobility of lung adenocarcinoma cell line H1299 and that this occurs via regulation of FA dynamics, changes in actin cytoskeleton organization and cell polarity.


Assuntos
Citoesqueleto de Actina/metabolismo , Movimento Celular , Citoplasma/metabolismo , Adesões Focais/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Polaridade Celular , Regulação para Baixo , Elasticidade , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Microscopia Confocal , Miosina Tipo II/metabolismo , Interferência de RNA , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Fibras de Estresse/metabolismo , Imagem com Lapso de Tempo/métodos , Viscosidade
4.
Clin Case Rep ; 12(11): e9510, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39464802

RESUMO

Key Clinical Message: Lumbar facet fracture-dislocation is rare, often due to hyperflexion with rotational force. Abnormal scoliosis on radiography is a key sign, prompting further imaging. Facetectomy and laminectomy ensure safe reduction, while instrumented fusion is an effective surgical treatment. Abstract: Traumatic lumbar facet dislocation is an uncommon condition, particularly when unilateral lumbar facet dislocation is accompanied by a contralateral facet fracture. The patient had a locked facet joint at the left L4-L5, a fracture of the right superior articular process of L5 and a comminuted fracture at the peritrochanteric region of the right femur following a fall. Emergent operation was conducted, starting with open reduction and fixation for the right proximal femur, followed by posterior open reduction and posterolateral fusion with instrumentation, without interbody fusion, for the lumbar spine injury. The patient exhibited positive outcomes throughout the follow-up. This article highlights the trauma mechanism of lumbar facet dislocation, emphasizing hyperflexion with rotational force. Abnormal local scoliosis is a distinctive imaging sign of facet joint dislocation. Facetectomy and laminectomy are recommended for safe reduction and instrumented fusion is considered a safe and effective surgical treatment for facet joint dislocation injuries.

5.
Nurse Educ Today ; 112: 105327, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35303544

RESUMO

BACKGROUND: Online learning in nursing education has been demonstrated to exert positive effects on knowledge, skills, learning attitudes, and confidence in performance. However, a noteworthy caveat has been that such benefits could vary depending on the content of pedagogical materials. AIM: To examine the impact of online-tutorials in place of face-to-face tutorials on knowledge level and understand the perspectives of learners who experience online-tutorials. METHODS: This study adopted a mixed method experiential design in which the perspectives of learners who experience online-tutorials are embedded within the trial. Two cohort of nursing students enrolled for the module on Psychology for Nurses were recruited to evaluate the impact of online-tutorials compared to face-to-face tutorials in terms of knowledge level. Apart from the dissimilar mode of delivery, both cohorts experienced the same teaching structure, content, and assessments. Examination results from these two cohorts were compared upon completion of the course. For the online group, additional one-to-one interviews were conducted to further understand the impacts exerted by online learning on the level of knowledge among them. RESULTS: There was a significant difference between the knowledge level of the two cohorts. Responses elicited during the interviews revealed five themes: lack of motivation; limited teamwork; missed learning opportunities; decreased interactions; and differences between online and face-to-face learning. CONCLUSION: Online-tutorials may be a feasible pedagogical approach but the motivation to learn, teamwork and quality of discussion may be compromised due to the lack of socialization and interactions between students and tutors.


Assuntos
Educação a Distância , Estudantes de Enfermagem , Atitude , Estudos de Coortes , Humanos , Aprendizagem , Estudantes de Enfermagem/psicologia
6.
J Chin Med Assoc ; 83(3): 245-250, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31972832

RESUMO

BACKGROUND: Pulmonary embolism (PE) is frequently associated with cancer. This study aimed to assess patients with acute PE and identify diagnostic predictors of new cancer after 1 year of follow-up. METHODS: One hundred and twenty-one patients with PE were enrolled consecutively from the emergency department of a single medical center in Taiwan. Data from computed tomography angiography, echocardiogram, electrocardiogram and for baseline comorbidities, clinical presentation, and laboratory parameters were recorded. The surviving discharged patients without a cancer diagnosis were followed-up for 1 year, and new malignancies were recorded. RESULTS: Of 121 patients with acute PE, 44 (36%) had an underlying cancer history (cancer group), and 77 (64%) did not (noncancer group). Baseline demographic characteristics, comorbidities, clinical symptoms, biochemical parameters, echocardiogram data, and electrocardiogram data of the two groups were similar except for a higher hospital mortality rate (56.8% vs 9.1%; p < 0.001), lower body mass index (22.6 ± 4.1 vs 25.5 ± 4.9; p =0.02), higher systolic blood pressure (139.7 ± 33.7 vs 125.4 ± 24.1; p = 0.02), lower low-density lipoprotein level (67.4 ± 38.3 vs 90.4 ± 33.8; p = 0.04), lower creatinine kinase (CK; 43.0 ± 43.0 vs 83.5 ± 83.1; p = 0.01), higher myocardial band (MB) form of CK ratio (0.2 ± 0.2 vs 0.1 ± 0.1; p < 0.01), higher partial pressure of arterial oxygen (122.81 ± 81.2 vs 90.2 ± 59.4; p = 0.03), and less presentation of chest pain (15.9% vs 40.3%; p = 0.01) in the cancer group. Kaplan-Meier curve analysis revealed that the 30-day survival rate was higher in the noncancer group than in the cancer group (log-rank p = 0.04). After 1 year of follow-up, 6 of 59 (10.17%) initial non-cancer-related PE survivors were diagnosed with malignancies. After multivariate analysis, only the initial CK-MB level was associated with a diagnosis of new cancer (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.029-1.811; p = 0.03). CONCLUSION: This study suggests that the CK-MB level is associated with future malignancy in patients with PE. Patients with cancer-related PE had a worse 30-day survival rate.


Assuntos
Neoplasias/complicações , Síndromes Paraneoplásicas/complicações , Embolia Pulmonar/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Creatina Quinase Forma MB/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estudos Prospectivos
7.
Life Sci Alliance ; 2(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30737247

RESUMO

Directed cell migration requires centrosome-mediated cell polarization and dynamical control of focal adhesions (FAs). To examine how FAs cooperate with centrosomes for directed cell migration, we used centrosome-deficient cells and found that loss of centrosomes enhanced the formation of acentrosomal microtubules, which failed to form polarized structures in wound-edge cells. In acentrosomal cells, we detected higher levels of Rac1-guanine nucleotide exchange factor TRIO (Triple Functional Domain Protein) on microtubules and FAs. Acentrosomal microtubules deliver TRIO to FAs for Rac1 regulation. Indeed, centrosome disruption induced excessive Rac1 activation around the cell periphery via TRIO, causing rapid FA turnover, a disorganized actin meshwork, randomly protruding lamellipodia, and loss of cell polarity. This study reveals the importance of centrosomes to balance the assembly of centrosomal and acentrosomal microtubules and to deliver microtubule-associated TRIO proteins to FAs at the cell front for proper spatial activation of Rac1, FA turnover, lamillipodial protrusion, and cell polarization, thereby allowing directed cell migration.


Assuntos
Movimento Celular/fisiologia , Polaridade Celular/fisiologia , Centrossomo/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Actinas/metabolismo , Adesão Celular/fisiologia , Linhagem Celular , Adesões Focais/metabolismo , Técnicas de Silenciamento de Genes , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Pseudópodes/metabolismo , Epitélio Pigmentado da Retina/citologia , Transfecção
8.
IEEE Trans Inf Technol Biomed ; 11(3): 296-304, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17521079

RESUMO

Direct visualization of synapses is a prerequisite to the analysis of the spatial distribution patterns of synaptic systems. Such an analysis is essential to the understanding of synaptic circuitry. In order to facilitate the visualization of individual synapses at the subcellular level from microscope images, we have introduced a wavelet-based approach for the semiautomated recognition of axonal synaptic varicosities. The proposed approach to image analysis employs a family of redundant wavelet representations. They are specifically designed for the recognition of signal peaks, which correspond to the presence of axonal synaptic varicosities. In this paper, the two-dimensional image of an axon together with its synaptic varicosities is first transformed into a one-dimensional (1-D) profile in which the axonal varicosities are represented by peaks in the signal. Next, by decomposing the 1-D profile in the differential wavelet domain, we employ the multi-scale point-wise product to distinguish between peaks and noises. The ability to separate the true signals (due to synaptic varicosities) from noise makes possible a reliable and accurate recognition of axonal synaptic varicosities. The proposed algorithms are also designed with a variable threshold that effectively allows variable sensitivities in varicosity detection. The algorithm has been systematically validated using images containing varicosities (< or =30) that have been consistently identified by seven human observers. The proposed algorithm can give high sensitivity and specificity with appropriate threshold. The results have indicated that the semiautomatic approach is satisfactory for processing a variety of microscopic images of axons under different conditions.


Assuntos
Algoritmos , Inteligência Artificial , Axônios/ultraestrutura , Cerebelo/ultraestrutura , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia/métodos , Reconhecimento Automatizado de Padrão/métodos , Sinapses/ultraestrutura , Animais , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
9.
Oncotarget ; 8(41): 70653-70668, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050309

RESUMO

Directed cell migration is an important step in effective wound healing and requires the dynamic control of the formation of cell-extracellular matrix interactions. Plasma fibronectin is an extracellular matrix glycoprotein present in blood plasma that plays crucial roles in modulating cellular adhesion and migration and thereby helping to mediate all steps of wound healing. In order to seek safe sources of plasma fibronectin for its practical use in wound dressing, we isolated fibronectin from human (homo) and porcine plasma and demonstrated that both have a similar ability as a suitable substrate for the stimulation of cell adhesion and for directing cell migration. In addition, we also defined the N-glycosylation sites and N-glycans present on homo and porcine plasma fibronectin. These N-glycosylation modifications of the plasma fibronectin synergistically support the integrin-mediated signals to bring about mediating cellular adhesion and directed cell migration. This study not only determines the important function of N-glycans in both homo and porcine plasma fibronectin-mediated cell adhesion and directed cell migration, but also reveals the potential applications of porcine plasma fibronectin if it was applied as a material for clinical wound healing and tissue repair.

10.
Brain Res Bull ; 70(1): 49-54, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16750482

RESUMO

Understanding synaptic connectivity is a prerequisite to gaining insight on how the central nervous system processes information. Cerebellar parallel fibers make an impressive number of synapses with the Purkinje cells. These synapses are the major structural elements of a large information processing system. The objective of the present report is to describe a method to estimate the coding capacity of this information processing system. We propose to derive the coding capacity from the linear distribution pattern of synaptic varicosities along parallel fibers in a manner consistent with Shannon's information theory formalism. The coding capacity of an average parallel fiber synapse is S=-kappaSigmaP(l(i))lnP(l(i)), where kappa=1/ln2, P(l(i)) is the probability of observing a particular inter-varicosital distance l(i), and ln is the natural logarithm to the base e. In the cerebellar parallel fibers of the mouse, and in a number of other unmyelinated axonal systems, the distribution pattern of P(l(i)) as a function of l(i) is exponential-like. According to information theory, the exponential-like distribution pattern suggests that information transmission in these axonal synaptic systems is operating at near-optimal coding capacity. This optimization in information coding may be the result of a stochastic-like process regulating the formation or elimination of parallel fiber synapses during development and maturation. In the adult nervous system, neuroplasticity-mediated synaptic remodeling may also regulate the coding capacity of axonal synapses via a similar stochastic-like process. The conceptual framework herein may be applicable to other axonal systems in the nervous system.


Assuntos
Cerebelo/citologia , Processamento Eletrônico de Dados , Fibras Nervosas/fisiologia , Animais , Cerebelo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Fibras Nervosas/ultraestrutura , Células de Purkinje/fisiologia , Células de Purkinje/ultraestrutura , Coloração pela Prata/métodos , Sinapses/fisiologia , Sinapses/ultraestrutura
11.
Brain Res Bull ; 64(1): 15-24, 2004 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-15275952

RESUMO

The length of cerebellar parallel fibers is important for information integration by the Purkinje cells. Based on the Copernican principle for analyzing the length of stochastic events, we have recently devised a stochastic method to estimate the mean length of parallel fibers within a given cerebellar region. The purpose of the present report is to provide validation of this methodology via computational simulations. We create virtual parallel fibers with known lengths and program each step of our stochastic method for computational simulation. We then compare the observed mean length obtained from our computational simulation with the known mean length of the virtual parallel fibers. In particular, we investigate the effect of cutting parallel fibers into segments during histological sectioning. Our computational results reveal an over-estimation factor ranging from 1.0 (no correction is necessary) to 2.0 as the parallel fiber segmentation becomes increasingly severe. Based on probability theory considerations, we have confirmed the existence of this over-estimation. We have further determined the cause of this over-estimation to be an artificial consequence of one of the sampling steps in our stochastic method. These results provide validation of our methodology, as well as a correction factor, which can be derived directly from the experimentally measured parameters and used to obtain the true mean length of parallel fibers. Potential applications of the stochastic method include a comparative analysis of the length of parallel fibers as an approach to gain clues about cerebellar circuit principles and function. In addition, the stochastic method may also find promising applications in other functionally important axonal systems in the brain.


Assuntos
Córtex Cerebelar/anatomia & histologia , Biologia Computacional/métodos , Modelos Neurológicos , Fibras Nervosas/fisiologia , Probabilidade , Simulação por Computador , Humanos , Funções Verossimilhança , Reprodutibilidade dos Testes , Processos Estocásticos
12.
Int J Cardiol ; 177(1): 86-90, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25499347

RESUMO

BACKGROUND: Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients. METHODS: In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes. RESULTS: A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04-1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74-1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06-1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence. CONCLUSIONS: The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Insuficiência Cardíaca/complicações , Hospitalização/tendências , Vigilância da População , Medição de Risco/métodos , Feminino , Seguimentos , Peptídeo 1 Semelhante ao Glucagon , Insuficiência Cardíaca/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Pontuação de Propensão , Pirazinas , Estudos Retrospectivos , Fatores de Risco , Fosfato de Sitagliptina , Taiwan/epidemiologia , Triazóis
13.
Am J Cardiol ; 113(4): 631-6, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24360773

RESUMO

The Food and Drug Administration recently updated the safety warning concerning the association between statin therapy and new-onset diabetes mellitus (NODM). For prediabetes, little information is available for statins on cardiovascular outcome reduction and diabetogenic consequences. This study aimed to examine the risk of NODM and the reduction of cardiovascular events and death (MACE) after statin therapy in the prediabetic subjects. The medical and pharmacy claims of the prediabetic beneficiaries were retrieved from Taiwan National Health Insurance research database. The occurrence of NODM, MACE, and morbidity indexed by hospitalizations and emergency visits was ascertained by ambulatory and inpatient database. A propensity score-matched model was constructed for statin users and nonusers. During follow-up (4.1 ± 2.5 years), NODM and MACE occurred in 23.5% and 16.7%, respectively, of nonusers and 28.5% and 12.0%, respectively, of users. Statin therapy was associated with a greater risk of NODM (hazard ratio 1.20, 95% confidence interval 1.08 to 1.32) and less risk of MACE (hazard ratio 0.70, 95% confidence interval 0.61 to 0.80), both in dose-dependent fashions. The earlier and more persistent use correlated with the greater increase in risk of NODM offset by the proportionally larger reduction in MACE. Furthermore, the early persistent users had the lowest rate of hospitalizations and emergency visits. In conclusion, our findings suggested that the relation between NODM and therapeutic advantages of statins was parallel in the prediabetic population. Treatment benefits outweighed diabetic consequences in subjects receiving the earlier and more persistent treatment.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Medição de Risco , Análise de Sobrevida
14.
Int J Cardiol ; 167(5): 2162-6, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22709730

RESUMO

BACKGROUND: The risk of incident cancer after angiotensin II receptor blockers (ARBs) exposure was controversially reported by analyses of clinical trials and database. We assessed the occurrence of overall and site-specific cancers among ARB users and nonusers in the cohort with indications for ARB treatment. METHODS: Data were obtained from the Taiwan National Health Insurance research database. Subjects exposed to ARBs ≥ 180 days with no cancer prior to the first year of ARB initiation were identified; age-, sex-, comorbidity- and time-matched nonusers without cancer before the index date plus 1 year were selected. Incidences of overall and the most common cancers between users and nonusers were compared. RESULTS: There were 42,921 subjects enrolled in each group. During the mean follow-up of 4.8 ± 2.4 years, the cumulative incidence of cancer was 4% (ARB users) and 6% (ARB nonusers) (hazard ratio: 0.58, 95% confidence intervals 0.55-0.62; P<0.001). All ARBs significantly correlated with lower rates of cancer. Malignancies from the 7 most common sites were fewer in ARB users with the relative risk reduction of 28 to 49%. ARBs were associated with a decrease in incident cancer across subgroups including prior and concomitant exposure to angiotensin-converting enzyme inhibitors. CONCLUSIONS: In the cohort with indications for ARB treatment, exposure to ARBs was associated with lower risk of overall and site-specific cancers compared to nonusers. These findings reassure the safety of ARBs and support further investigations on ARBs and cancer prevention at the molecular level.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Vigilância da População/métodos , Idoso , Estudos de Coortes , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo
15.
Biomaterials ; 34(18): 4501-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23498892

RESUMO

Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Polímeros/síntese química , Temperatura , Ácido Aminocaproico/síntese química , Ácido Aminocaproico/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Injeções , Cinética , Luz , Masculino , Camundongos , Camundongos Nus , Micelas , Nanopartículas/ultraestrutura , Neoplasias/patologia , Tamanho da Partícula , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polímeros/química , Espalhamento de Radiação , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Anal Methods Chem ; 2012: 936131, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22567575

RESUMO

HPLC in combination with automated analytical system and ESI/MS/MS was used to analyze aconitine (A), mesaconitine (MA), hypaconitine (HA), and their benzoyl analogs in the Chinese herbs Caowu and Chuanwu. First, an HPLC method was developed and validated to determine A, MA, and HA in raw and processed Caowu and Chuanwu. Then an automated analytical system and ESI/MS/MS were applied to analyze these alkaloids and their semihydrolyzed products. The results obtained from automated analytical system are identical to those from ESI/MS/MS, which indicated that the method is a convenient and rapid tool for the qualitative analysis of herbal preparations. Furthermore, HA was little hydrolyzed by heating processes and thus it might account more for the toxicity of processed aconites. Hence, HA could be used as an indicator when one alkaloid is required as a reference to monitor the quality of raw and processed Chuanwu and Caowu. In addition, the raw and processed Chuanwu and Caowu can be distinguished by monitoring the ratio of A and MA to HA.

17.
J Am Coll Cardiol ; 60(14): 1231-8, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-22884288

RESUMO

OBJECTIVES: This study aimed to evaluate the association of statin exposure and incident diabetes, and subsequent outcomes in the general population. BACKGROUND: Cardiovascular events as consequences of atherosclerosis and diabetes are reduced by statins. However, statins are associated with excessive risk of diabetes occurrence according to clinical trial analyses. From daily-practice perspectives, it remains unclear whether statin use increases risk; prognoses of diabetes after exposure require further clarification. METHODS: From Taiwan National Health Insurance beneficiaries age ≥45 years (men) and ≥55 years (women) before 2004, subjects continuously treated with statins ≥30 days during 2000 to 2003 and nonusers before 2004 were identified. Among nondiabetic individuals at the cohort entry, controls were matched to statin users on a 4:1 ratio by age, sex, atherosclerotic comorbidities, and year of their entry. Outcomes as diabetes, major adverse cardiovascular events (MACE, the composite of myocardial infarction and ischemic stroke), and in-hospital deaths were assessed. RESULTS: Over a median of 7.2 years, annual rates of diabetes were significantly higher in statin users (2.4% vs. 2.1%, p < 0.001), whereas MACE (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.68 to 0.98 for myocardial infarction; HR: 0.94; 95% CI: 0.86 to 1.03 for ischemic stroke; HR: 0.91; 95% CI: 0.84 to 0.99 for MACE]) and in-hospital mortality (HR: 0.61; 95% CI: 0.55 to 0.67]) were less. The risk-benefit analyses suggested that statin treatment was favorable in high-risk (HR: 0.89; 95% CI: 0.83 to 0.95) and secondary prevention (HR: 0.89; 95% CI: 0.83 to 0.96) populations. Among diabetic patients, prior statin use was associated with fewer MACE (HR: 0.75; 95% CI: 0.59 to 0.97). In-hospital deaths were similar in statin-related diabetes among high-risk (HR: 1.11; 95% CI: 0.83 to 1.49) and secondary prevention (HR: 1.08; 95% CI: 0.79 to 1.47) subjects compared with nondiabetic controls. CONCLUSIONS: Risk of diabetes was increased after statins, but outcomes were favorable.


Assuntos
Doença das Coronárias/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Doença das Coronárias/prevenção & controle , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
18.
Am J Hypertens ; 24(7): 775-82, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21372800

RESUMO

BACKGROUND: The role of pulsatile hemodynamics in the management of patients with acute heart failure syndrome (AHFS) remains to be elucidated. We investigated the changes of the pulsatile hemodynamics along the hospital course of AHFS in relation to short-term outcomes. METHODS: A total of 80 AHFS patients (73.2 ± 14.1 years, 82.5% men) were enrolled and followed up for up to 6 months after discharge. Measures of the pulsatile hemodynamics including brachial and central systolic blood pressure (SBP) and pulse (PP) pressure, carotid-femoral pulse wave velocity (cf-PWV), carotid augmentation index (cAI and cAI(75)) and carotid augmented pressure (cAP) were obtained within 24 h of admission, before discharge, and 2 weeks after discharge. RESULTS: During a follow-up of 174 ± 32 days (16-183 days), 29 patients experienced events including rehospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and mortality. Predischarge brachial and central PP, and cAP, and postdischarge brachial and central SBP and PP, cAP, and cf-PWV were significantly lower in patients without events than those with events. Predischarge central PP (hazard ratio per 1-s.d. and 95% confidence interval: 1.62 (1.12-2.34)) and cAP (1.47 (1.05-2.05)) predicted events independent of age and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Similarly, postdischarge brachial and central SBP and PP, cAP, and cf-PWV were also significant independent predictors. CONCLUSION: Suboptimal recovery of the perturbations of the pulsatile hemodynamics in patients hospitalized due to AHFS may relate to adverse short-term outcomes and warrant aggressive treatment.


Assuntos
Pressão Sanguínea/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Fluxo Pulsátil/fisiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiopatologia , Artérias Carótidas/fisiopatologia , Feminino , Artéria Femoral/fisiopatologia , Seguimentos , Insuficiência Cardíaca/mortalidade , Frequência Cardíaca/fisiologia , Humanos , Masculino , Readmissão do Paciente , Prognóstico , Acidente Vascular Cerebral , Taxa de Sobrevida
19.
Clin Biochem ; 44(13): 1110-1115, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21723271

RESUMO

OBJECTIVES: Pulmonary embolism is a common disease associated with a high mortality rate. The risk assessment and appropriate treatment selection of patients with acute pulmonary embolism remains a challenge. DESIGN AND METHODS: This single center cohort study included a total of 150 patients (96 male, age = 71 ± 15 years) with acute pulmonary embolism confirmed by spiral-computed tomography or magnetic resonance image. The prognostic performance of the clinical characteristics and laboratory values were investigated to predict the in-hospital hemodynamically instable events and 30-day all-cause mortality. RESULTS: The rate of in-hospital hemodynamic instability and 30-day all-cause mortality was 21% and 12%, respectively. A multivariate Cox regression analysis demonstrated that a heart rate ≥ 110 bpm (odd ratio 4.26 [95% CI 1.42-12.77]), chronic pulmonary disease (6.47 [1.99-21.04]), WBC ≥ 11,000 mm(3) (3.78 [1.32-10.82]), and D-dimer level ≥ 4.0 µg/mL (3.68 [1.01-13.43]) independently predicted the 30-day fatal outcome. A Kaplan-Meier survival analysis showed that the categorization based on the number of risk factors was significantly associated with the likelihood of 30-day all-cause mortality (P<0.0001). CONCLUSIONS: The initial presentation of tachycardia, presence of chronic pulmonary disease, elevated WBC and D-dimer on admission can be used to identify the risk for a short-term fatal outcome within 30 days in patients with acute pulmonary embolism.


Assuntos
Embolia Pulmonar/diagnóstico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Contagem de Leucócitos , Pneumopatias , Masculino , Pessoa de Meia-Idade , Prognóstico , Embolia Pulmonar/mortalidade , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Taquicardia , Resultado do Tratamento
20.
J Hypertens ; 29(3): 454-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21252703

RESUMO

OBJECTIVES: Central systolic (SBP-C) and/or pulse pressure (PP-C) better predicts cardiovascular events than does peripheral blood pressure. The present study compared the prognostic significance of office central blood pressure with multiple measurements of out-of-office ambulatory peripheral blood pressure, with reference to office peripheral systolic (SBP-B) or pulse pressure (PP-B). METHODS: In a community-based population of 1014 healthy participants, SBP-C and PP-C were estimated using carotid tonometry, and 24-h systolic (SBP-24 h) and pulse pressure (PP-24 h) were obtained from 24-h ambulatory blood pressure monitoring. Associations of SBP-B, PP-B, SBP-C, PP-C, SBP-24 h, and PP-24 h with all-cause and cardiovascular mortalities over a median follow-up of 15 years were examined by Cox regression analysis. RESULTS: In multivariate analyses accounting for age, sex, BMI, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein cholesterol ratio, only PP-C (hazard ratio 1.16, 95% confidence interval 1.01-1.32, per one standard deviation increment) was significantly predictive of all-cause mortality, whereas all but PP-B were significantly predictive of cardiovascular mortality. When SBP-B was simultaneously included in the models, SBP-24 h (2.01, 1.42-2.85) and SBP-C (1.71, 1.21-2.40) remained significantly predictive of cardiovascular mortality. When SBP-C was simultaneously included in the models, SBP-24 h (1.71, 1.16-2.52) remained significantly predictive of cardiovascular mortality. CONCLUSION: Office central blood pressure is more valuable than office peripheral blood pressure in the prediction of all-cause and cardiovascular mortalities. Out-of-office ambulatory peripheral blood pressure (SBP-24 h) may be superior to central blood pressure in the prediction of cardiovascular mortality, but PP-C may better predict all-cause mortality than SBP-24 h or PP-24 h.


Assuntos
Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Doenças Cardiovasculares/mortalidade , Adulto , Fatores Etários , Idoso , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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