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BACKGROUND: The ageing population and the changing disease profile have been driving the demand for community nurses. However, few nursing students in Singapore aspire to have a career in community nursing following graduation. OBJECTIVES: To explore undergraduate nursing students' perceptions of a career in community nursing and to identify strategies to promote community nursing among nursing students. METHODS: An exploratory qualitative design was used. Four focus group discussions were conducted with a purposive sample of 24 undergraduate nursing students from a university. Interview transcripts were analysed using thematic analysis. FINDINGS: Four key themes emerged as follows: 'mid-life career', 'limited career progression', 'a difficult transition' and 'international nurses-dominated workforce'. DISCUSSION: While most participants rejected a career in community nursing immediately after graduation, they planned to join it at the later stages of their lives to accommodate changing life priorities. Limited career progression and increased difficulty in career transition from community nursing to acute care nursing were identified as deterrent factors in the participants' choices of community nursing as a career. Feelings of marginalization and a lack of role models in community nursing were perceived to be the result of the international nurses-dominated community workforce. CONCLUSION: Community nursing remains an underrated career. There is a need to foster an optimistic career outlook and mobility in community nursing to entice nursing students into this career track. IMPLICATIONS FOR NURSING POLICY: Strategies to enhance community nursing recruitment should focus on providing more quality and diverse community placement opportunities in various community care settings, implementing a clearly defined career developmental plan to elucidate the role of community nurses, and improving community care and cultural competencies to develop a skilled and diverse community nursing workforce.
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Escolha da Profissão , Enfermagem em Saúde Comunitária/educação , Estudantes de Enfermagem/psicologia , Mobilidade Ocupacional , Bacharelado em Enfermagem , Feminino , Grupos Focais , Humanos , Masculino , Pesquisa Qualitativa , Singapura , Adulto JovemRESUMO
Our previous studies showed that the alcohol extract of the fruit of Brucea javanica (Fructus Bruceae) possessed significant cytotoxicity in pancreatic adenocarcinoma cell lines. A bioassay-guided fractionation and purification resulted in the isolation and characterization of seven quassinoids including brusatol, bruceine D, bruceine H, yadanzioside A, yadanzioside G, javanicoside C and bruceantinoside A. Among them, brusatol exhibited the most potent in vitro antipancreatic cancer action, with IC(50) values of 0.36 µm and 0.10 µm on PANC-1 and SW1990 cell lines, respectively. This is the first report on the antipancreatic adenocarcinoma activity of brusatol.
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Antineoplásicos Fitogênicos/farmacologia , Brucea/química , Neoplasias Pancreáticas/patologia , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Frutas/química , Humanos , Concentração Inibidora 50 , Plantas Medicinais/química , Quassinas/isolamento & purificaçãoRESUMO
OBJECTIVE. To report the initial experience in using cryoballoon catheter ablation in the treatment of atrial fibrillation in Hong Kong. DESIGN. Single-centre, prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. Sixteen patients (mean age, 55 years; standard deviation, 14 years; 11 males) with paroxysmal (n=12) or persistent (n=4) atrial fibrillation. INTERVENTIONS. Pulmonary vein isolation by ablation with a 28-mm cryoballoon catheter. MAIN OUTCOME MEASURES. Safety, effectiveness, and learning curve of this procedure. RESULTS. Of 67 pulmonary veins, 61 (91%) could be successfully isolated with the cryoballoon alone. The remaining pulmonary veins were isolated with additional ablation using an 8-mm tip cryocatheter. One phrenic nerve palsy developed during right middle pulmonary vein ablation, which resolved. Another patient endured a minor guidewire dissection of the right inferior pulmonary vein. The mean (standard deviation) procedural and fluoroscopic times were 231 (32) and 62 (18) minutes, respectively. On comparing the first nine and last seven procedures, there was a significant improvement in procedural time (mean [standard deviation], 244 [32] vs 213 [24] minutes; P=0.04) and in the fluoroscopic time (70 [21] vs 51 [7] minutes; P=0.038). With a median follow-up of 21 months, nine (75%) of the 12 patients with paroxysmal atrial fibrillation and one (25%) of those four with persistent atrial fibrillation had no recurrence, without the use of anti-arrhythmic drugs. CONCLUSIONS. Pulmonary vein isolation by cryoballoon catheter ablation is safe and effective in treating patients with paroxysmal, but not for patients with persistent atrial fibrillation. A relatively short learning curve of around 10 cases was deemed appropriate.
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Fibrilação Atrial/cirurgia , Ablação por Cateter , Criocirurgia , Veias Pulmonares/cirurgia , Adulto , Idoso , Oclusão com Balão , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Feminino , Fluoroscopia , Seguimentos , Hong Kong , Humanos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de TempoRESUMO
BACKGROUND: In human pancreatic adenocarcinoma, nuclear factor-kappa-B (NF-kappaB) transcription factor is constitutively activated that contributes to the resistance of the tumour cells to induced apoptosis. In our earlier studies, we have shown that brucein D (BD) mediated apoptosis through activation of the p38-mitogen-activated protein kinase (MAPK) signalling pathway in pancreatic cancer cells. This study investigated the function of reactive oxygen species (ROS) in BD-mediated p38-MAPK and NF-kappaB signalling pathways in PANC-1 cells. METHODS: Glutathione and dihydroethidium assays were used to measure the antioxidant and superoxide levels, respectively. The protein expression of p22(phox), p67(phox) and p38-MAPK were examined by western blot. The NF-kappaB activity was evaluated by electrophoretic mobility shift assay. RESULTS: Treatment with BD depleted the intracellular glutathione levels in PANC-1 cells. Brucein D triggered the activation of NADPH oxidase isoforms, p22(phox) and p67(phox) while enhancing the generation of superoxide. Increases in both intracellular ROS and NADPH oxidase activity were inhibited by an antioxidant, N-acetylcysteine (NAC). Brucein D-mediated activation of p38-MAPK was also inhibited by NAC. However, inhibition of NF-kappaB activity in BD-treated cells was independent of ROS. In vivo studies showed that BD treatment effectively reduced the rate of xenograft human pancreatic tumour in nude mice with no significant toxicity. CONCLUSION: These data suggest that BD is an apoptogenic agent for pancreatic cancer cells through activation of the redox-sensitive p38-MAPK pathway and inhibition of NF-kappaB anti-apoptotic activity in pancreatic cancer cells.
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Adenocarcinoma/tratamento farmacológico , NF-kappa B/fisiologia , Neoplasias Pancreáticas/tratamento farmacológico , Quassinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Adenocarcinoma/metabolismo , Animais , Linhagem Celular Tumoral , Ensaio de Desvio de Mobilidade Eletroforética , Glutationa/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NADPH Oxidases/fisiologia , Neoplasias Pancreáticas/metabolismo , Quassinas/uso terapêutico , Superóxidos/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This paper describes the design and testing of a trommel for separation of batteries from solid waste. A trommel is a cylindrical separation device that rotates and performs size separation. It has also been used in areas such as municipal solid waste (MSW) processing, classifying construction and demolition debris, screening mass-burn incinerator ash and compost processing. A trommel has been designed based on size separation to separate household batteries from solid waste, which can then be used as feedstock for alternative applications of solid waste combustion, particularly where the metal content of the product is also a critical parameter, such as the Co-Co process for integrated cement and power production. This trommel has been tested with batches of university office and restaurant wastes against various factors. The recovery efficiency of batteries increases with decreasing inclination angle of the trommel and decreasing rotational speed. A physical characterization of the university solid waste has been performed with a 20-kg sample of the tested waste. It was found that there is a trend of decreasing recovery of batteries with increasing paper composition, and a trend of increasing recovery of batteries with increasing organic materials composition.
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Manufaturas , Eliminação de Resíduos/instrumentação , Eliminação de Resíduos/métodos , Universidades , Resíduos/análiseRESUMO
High cellular heterogeneity within neuroblastomas (NBs) may account for the non-uniform response to treatment. c-KIT(+) cells are frequently detected in NB, but how they influence NB behavior still remains elusive. Here, we used NB tumor-initiating cells to reconstitute NB development and demonstrated that c-KIT(+) cells are de novo generated and dynamically maintained within the tumors to sustain tumor progression. c-KIT(+) NB cells express higher levels of neural crest and stem cell markers (SLUG, SOX2 and NANOG) and are endowed with high clonogenic capacity, differentiation plasticity and are refractory to drugs. With serial transplantation assays, we found that c-KIT expression is not required for tumor formation, but c-KIT(+) cells are more aggressive and can induce tumors ninefold more efficiently than c-KIT(-/low) cells. Intriguingly, c-KIT(+) cells exhibited a long-term in vivo self-renewal capacity to sustain the formation of secondary and tertiary tumors in mice. In addition, we showed that Prokineticin signaling and mitogen-activated protein kinase pathways are crucial for the maintenance of c-KIT(+) cells in tumor to promote NB progression. Our results highlight the importance of this de novo population of NB cells in sustainable growth of NB and reveal specific signaling pathways that may provide targets leading to more effective NB therapies.
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Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neuroblastoma/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/fisiologia , Animais , Proliferação de Células , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Neuroblastoma/genética , Neuroblastoma/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Alendronate, a bisphosphonate drug, has shown promise in reducing remodeling and bone loss in postmenopausal osteoporosis. Alendronate acts directly on the osteoclast, inhibiting its resorption capability. This inhibition of osteoclast activity has led to the use of bisphosphonates in the treatment of the osteogenesis imperfecta condition. Treatment of osteogenesis imperfecta with bisphosphonates enhances bone strength, but the consequences on linear bone growth are not well defined. Using the oim mouse model for type III osteogenesis imperfecta, two doses of alendronate, low (0.125 mg/kg/wk) and high (2.5 mg/kg/wk) were administered weekly via intraperitoneal injection starting at 4 weeks of age and ending at 12 weeks of age to assess the effects of alendronate on humerus and ulna length. The higher dose of alendronate reduced humerus and ulna length in the oim/wt and wt/wt genotypes for both sexes (P < 0.05). The oim/oim humerus and ulna were not significantly affected by the higher dose of alendronate in females, but reduced bone length in males (P < 0.0085). Proximal humerus growth plate area was affected by both genotype and alendronate dose and growth plate diameter was increased at the chondro-osseous junction by both alendronate doses (P < 0.011). Genotype and alendronate dose affected growth plate height. The oim/oim genotype displayed taller growth plates. The high dosage of alendronate increased overall growth plate height, particularly within the hypertrophic zone, which suggests a failure of vascular invasion-induced apoptosis in the hypertrophic cells. In conclusion, these results indicate that high doses of alendronate (>2.5 mg/kg/wk) inhibit long bone length in mice through alteration of the growth plate and possibly reduced resorption at the chondro-osseous junction.
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Alendronato/farmacologia , Desenvolvimento Ósseo/efeitos dos fármacos , Lâmina de Crescimento/efeitos dos fármacos , Osteogênese Imperfeita/tratamento farmacológico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Genótipo , Lâmina de Crescimento/patologia , Úmero/efeitos dos fármacos , Úmero/crescimento & desenvolvimento , Úmero/patologia , Masculino , Camundongos , Camundongos Mutantes , Osteogênese Imperfeita/patologia , Ulna/efeitos dos fármacos , Ulna/crescimento & desenvolvimento , Ulna/patologiaRESUMO
There is evidence that the collagen microarchitecture of bone is influenced by mechanical stresses or strains. We hypothesized that peak functional strains correlate with the elastic anisotropy and collagen orientation of bone tissue and that the bone anisotropy might be changed by altering the strain patterns in canine radii for 12 months. We tested these hypotheses in studies using nine adult foxhounds. The baseline group (n = 3) had three rosette strain gauges placed around the midshaft of the radius, and strain distributions were measured during walking. The osteotomy group (n = 3) had 2 cm of the ulna surgically removed, and the sham group (n = 3) received a sham osteotomy. The osteotomy and sham groups were allowed free movement in cages with runs for 12 months, after which strain distributions were measured on the radii during walking. Bone-tissue anisotropy and collagen architecture were measured in radii from which the in vivo longitudinal strain patterns had been measured. The collagen birefringence patterns were measured with use of a circularly polarized light technique, and the elastic anisotropy of the bone, mineral, and collagen matrix was evaluated with a novel acoustic microscopy technique. Peak longitudinal strains in the radius correlated with the normalized longitudinal structure index (a polarized light measure of collagen birefringence) and the tissue anisotropy ratio. The average anisotropy ratio was 1.28+/-0.01 in the posterior (compressive) cortex and 1.43+/-0.01 in the anterior (tensile) cortex (these values are significantly different at p < 0.0001). The ulnar osteotomy changed the strain pattern on the radius, causing increased tensile strains in the medial cortex by more than 5-fold that were associated with a significant increase in the anisotropy ratio in the bone tissue. The longitudinal structure index was strongly correlated (r = 0.62, p < 0.005) with the anisotropy ratio of demineralized bone but was not correlated with that of deproteinized bone; this indicates that it reflects collagen fibril orientation in the bone matrix. These results indicate that mechanical strains affect both collagen and mineral microarchitecture in bone tissue, i.e., tensile strains are associated with increased tissue anisotropy and compressive strains, with decreased anisotropy.
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Colágeno/fisiologia , Osteotomia , Rádio (Anatomia)/fisiologia , Animais , Anisotropia , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Colágeno/ultraestrutura , Cães , Elasticidade , Microscopia de Polarização , Rádio (Anatomia)/cirurgia , Rádio (Anatomia)/ultraestrutura , Estresse Mecânico , Resistência à Tração , Ulna/fisiologia , Ulna/cirurgia , Ulna/ultraestruturaRESUMO
BACKGROUND: The end result of leakage of pancreatic juice into the peripancreatic space can be sterile necrosis, infected necrosis, or rupture into an adjacent hollow viscus or blood vessel (eg, colon, small bowel, or pseudoaneurysm). If a pancreatic duct (PD) leak is present, should treatment be aimed at minimizing the sequela of the leakage of pancreatic juice and not just supportive observation until a necrosectomy is required? METHODS: In 144 patients with severe pancreatitis we investigated whether the presence of a PD leak was associated with necrosis and also asked if PD leak might predict other outcomes such as a length of stay (LOS), mortality, and need for surgery. Furthermore, we questioned whether the use of endoscopic retrograde cholangiopancreatography (ERCP) to search for a PD leak might worsen the clinical outcome because of the potential for introducing microorganisms into an undrained space or exacerbating pancreatitis. RESULTS: The presence of a demonstrable pancreatic duct leak was observed in 37% of patients and was significantly associated with both a higher incidence of necrosis and prolonged LOS (> or = 20 days). These patients were 3.4 times more likely to have necrosis and 2.6 times more likely to have a prolonged LOS. When treated with a combination of percutaneous drains, pancreatic duct stents, and surgery as necessary, a PD leak (even with its higher necrosis rate) was not significantly correlated with either mortality or the need for necrosectomy. The use of ERCP was not associated with LOS, mortality, or the need for necrosectomy, provided discovered PD leaks were immediately drained. CONCLUSIONS: A PD leak is common in patients with pancreatic necrosis but it is also important to locate and decompress in order to impede progression of the disease and keep mortality low.
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Ductos Pancreáticos/patologia , Suco Pancreático , Pancreatite/complicações , Adulto , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade , Necrose , Ductos Pancreáticos/cirurgia , Pancreatite/cirurgia , Estudos Retrospectivos , Fatores de Risco , RupturaRESUMO
We studied birefringence as an indicator of collagen fiber orientation in the diaphysis of the equine third metacarpal bone. We had previously shown that tissue from the lateral cortex of this bone is stronger monotonically, but less fatigue resistant, than tissue from the medial and dorsal regions. To learn whether collagen fiber orientation might play a role in this regional specialization, we tested three hypotheses using the same specimens: (1) collagen fiber orientation is regionally dependent; (2) remodeling changes collagen fiber orientation; (3) longitudinal collagen fibers correlate positively with modulus and monotonic bending strength and negatively with flexural fatigue life. Beams (N = 36) cut parallel to the long axes of six pairs of bones had been tested to determine elastic modulus (N = 36), and fatigue life (N= 24) or monotonic strength (N = 12) in four-point bending. Subsequently, histologic cross-sections were prepared, and porosity, active remodeling and past remodeling were quantified. Birefringence was measured as an indicator of transverse collagen orientation using plane-polarized light (PPL), and again using circularly polarized light (CPL). The CPL measurement was less variable than the PPL measurement. Both birefringence measures indicated that collagen was more longitudinally oriented in the lateral cortex than in the other two cortices. Longitudinally disposed collagen correlated with greater modulus and monotonic strength, but did not correlate with fatigue life. Remodeling was associated with more transverse collagen. Neither measure of birefringence was significantly correlated with porosity. It was concluded that, in the equine cannon bone, longitudinal collage fiber orientation is regionally variable, contributes to increased modulus and strength but not fatigue life, and is reduced by osteonal remodeling.
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Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Osso e Ossos/ultraestrutura , Colágeno/fisiologia , Colágeno/ultraestrutura , Metacarpo/fisiologia , Metacarpo/ultraestrutura , Animais , Elasticidade , Fraturas de Estresse/fisiopatologia , Ósteon/fisiologia , Ósteon/ultraestrutura , Cavalos , Microscopia de Polarização/métodos , Maleabilidade , Porosidade , Estresse MecânicoRESUMO
BACKGROUND: Two cases of combined laparoscopic- assisted right hemicolectomy and low anterior resection for malignancy are presented to illustrate the technical aspects of performing two concurrent laparoscopic-assisted bowel resections with sequential anastomosis. Although there are similarities with laparoscopic-assisted total proctocolectomy, the need for complete mesenteric dissection in two areas, removal of two separate specimens containing malignancy, and the need for two anastomoses raise unique technical considerations which include port placement, sequence of dissection, choice of specimen extraction sites, specimen handling, and sites for extracorporeal anastomosis. METHODS: Operative notes, operative videotapes, and hospital inpatient and outpatient records were reviewed for both patients. RESULTS: Laparoscopic-assisted combined resection was completed in both patients. In both cases, laparoscopic total mesorectal excision was performed. Maximum incision length was 6 cm. Both patients were ready for discharge on postoperative day 3. CONCLUSION: Combined laparoscopic assisted right colectomy and low anterior resection can be performed for synchronous colorectal malignancies with curative intent.
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Anastomose Cirúrgica/métodos , Carcinoma/cirurgia , Neoplasias do Ceco/cirurgia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/cirurgia , Idoso , Colo Ascendente/cirurgia , Feminino , Humanos , Ileostomia , Masculino , Pessoa de Meia-Idade , Inoculação de Neoplasia , Manejo de EspécimesRESUMO
OBJECTIVE: To obtain information on prescription pattern of antipsychotic drugs for schizophrenic in-patients treated in public hospitals in Hong Kong. Four main areas of antipsychotic treatment are reported in this paper: (1) doses of antipsychotic drugs, (2) the practice of giving multiple antipsychotic agents simultaneously, (3) use of antipsychotics in divided daily doses and (4) co-administration of antipsychotic and antiparkinson drugs. METHODS: A cross-sectional survey of prescriptions of antipsychotic medication for a representative sample of 957 schizophrenic in-patients was conducted on a randomly chosen census day. Questionnaire items included basic demographic and clinical data, as well as inventory for all medications received by patients on census day. RESULTS: The mean antipsychotic dose was 854 +/- 759 (median: 600; range) 0-4450) mg CPZeq. Over two-third of the patients were given more than drug concurrently while less than 20% received the medication in multiple divided doses. Antiparkinson drugs were prescribed with antipsychotic medication in 69.61%, of the subjects. There were few differences between acute and chronic patients with respect to their respective prescription patterns. CONCLUSIONS: Antipsychotic treatment of schizophrenic inpatients in Hong Kong is largely in accord with international standards. Problematic areas identified for closer scrutiny include the concurrent use of more than one antipsychotic drug for both acute and chronic patients, and the higher than recommended doses for antipsychotic drugs and frequent use of antiparkinson medication for chronic patients. Dissemination of these results, accompanied by continuing medical education about psychopharmacology, are planned to further improve the quality of treatment for schizophrenic patients.
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Antiparkinsonianos/administração & dosagem , Antipsicóticos/administração & dosagem , Clorpromazina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adulto , Estudos Transversais , Esquema de Medicação , Quimioterapia Combinada , Uso de Medicamentos , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A survey was conducted to assess the long term outcome of 60 elderly stroke survivors (mean age, 81.7 years). Of these patients, 48% died within one year of discharge and 79% of the mortality occurred in the first six months. Patients discharged to institutions after the initial stroke had a significantly higher risk of death in one year (relative risk=1.47) compared with those who were discharged home. For those who survived for a mean period of 18.6months, 72% (21/29) were institutionalised. This group had significantly worse functional status and mobility compared with those who were living at home. The caring of elderly stroke patients was considered a heavy burden for most carers at home or in institutions and the need for medical and social support was great.
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Ticlopidine, an adenosine diphosphate receptor blocker, is widely used to prevent subacute stent thrombosis after percutaneous coronary intervention. Along with neutropenia and thrombotic thrombocytopenic purpura, cholestatic hepatitis is one of the most serious potential side-effects of ticlopidine therapy. Four patients with prolonged jaundice after ticlopidine therapy, including one fatal case, are presented. Alternative antithrombotic therapy for subsequent percutaneous coronary intervention is also described. Clopidogrel therapy was found to be safe and effective in two patients with a history of ticlopidine-related cholestatic hepatitis.
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Doença das Coronárias/terapia , Icterícia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Stents , Ticlopidina/efeitos adversos , Idoso , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Single-element, planar transducers have been fabricated using electron-irradiated poly(vinylidene fluoride-trifluoroethylene) 80/20 mol% copolymers with different electron dosage. Electrical field-induced strain response of copolymer film with 100 Mrad dosage has been studied at 5 kHz and the electrostrictive coefficient was calculated. The transmitting response of the air-backing and epoxy-backing transducers was evaluated with the application of high DC bias voltages. Clear ultrasonic amplitudes and high frequency spectrum (>20 MHz) were observed when driven from a standard ultrasonic voltage source through a decoupling circuit. It has also showed that larger generation of ultrasonic waves will be induced under high DC bias field, which is due to the increase of induced d(33) piezoelectric coefficient. Two different polar bias voltages, positive and negative, were applied to the transducers and inverse waveforms were received, which was coincident with the theoretical analysis of the strain response of electrostrictive film.
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Neuroblastoma (NB) is an embryonal tumor and possesses a unique propensity to exhibit either a spontaneous regression or an unrestrained growth. However, the underlying mechanism for this paradoxical clinical outcome remains largely unclear. Quantitative RT-PCR analysis on 102 primary NB tumors revealed that lower Krüppel-like factor 4 (KLF4) expression is frequently found in the unfavorable NB (Mann-Whitney test, P=0.027). In particular with the high-risk factors such as age of patient >1 year, MYCN amplification and low TRKA expression, the decreased expression of KLF4 was significantly associated with an unfavorable NB outcome. Despite knockdown of KLF4 alone is not sufficient to increase tumorigenicity of NB cells in vivo, stable expression of KLF4 short hairpin RNA in Be(2)-C cells significantly promoted growth of NB cells and inhibited cell differentiation toward fibromuscular lineage. In concordant with these observations, overexpression of KLF4 in SH-SY-5Y cells profoundly suppressed cell proliferation by direct upregulation of cell-cycle inhibitor protein p21(WAF1/CIP1), and knocking down p21(WAF1/CIP1) could partially rescue the suppressive effect of KLF4. Importantly, KLF4 overexpressing cells have lost their neuroblastic phenotypes, they were epithelial-like, strongly substrate-adherent, expressing smooth muscle marker and became non-tumorigenic, suggesting that KLF4 expression is crucial for lineage determination of NB cells, probably, favoring spontaneous tumor regression. Subsequent global gene expression profiling further revealed that transforming growth factor beta (TGFß) and cell-cycle pathways are highly dysregulated upon KLF4 overexpression, and myogenic modulators, MEF2A and MYOD1 were found significantly upregulated. Taken together, we have demonstrated that KLF4 contributes to the favorable disease outcome by directly mediating the growth and lineage determination of NB cells.
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Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Fatores de Transcrição Kruppel-Like/fisiologia , Neuroblastoma/patologia , Animais , Ciclo Celular , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/análise , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/análise , Camundongos , Proteína Proto-Oncogênica N-Myc , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Fator de Crescimento Transformador beta/genética , Proteína Supressora de Tumor p53/análiseRESUMO
Lead magnesium niobate-lead titanate single crystal 0.72Pb(Mg(13)Nb(23))O(3)-0.28PbTiO(3) (abbreviated as PMN-PT) was used to fabricate high performance ultrasonic phased-array transducer as it exhibited excellent piezoelectric properties. In this paper, we focus on the design and fabrication of a low-loss and wide-band transducer for medical imaging applications. A KLM model based simulation software PiezoCAD was used for acoustic design of the transducer including the front-face matching and backing. The calculated results show that the -6 dB transducer bandwidth can be improved significantly by using double lambda8 matching layers and hard backing. A 4.0 MHz PMN-PT transducer array (with 16 elements) was fabricated and tested in a pulse-echo arrangement. A -6 dB bandwidth of 110% and two-way insertion loss of -46.5 dB were achieved.
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In this work, a novel high-frequency ultrasonic transducer structure is realized by using PMNPT-on-silicon technology and silicon micromachining. To prepare the single crystalline PMNPT-on-silicon wafers, a hybrid processing method involving wafer bonding, mechanical lapping and wet chemical thinning is successfully developed. In the transducer structure, the active element is fixed within the stainless steel needle housing. The measured center frequency and -6 dB bandwidth of the transducer are 35 MHz and 34%, respectively. Owing to the superior electromechanical coupling coefficient (k(t)) and high piezoelectric constant (d(33)) of PMNPT film, the transducer shows a good energy conversion performance with a very low insertion loss down to 8.3 dB at the center frequency.
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BACKGROUND: Although heart failure with a preserved or normal ejection fraction (HFNEF or diastolic heart failure) is common, treatment outcomes on quality of life and cardiac function are lacking. The effect of renin-angiotensin blockade by irbesartan or ramipril in combination with diuretics on quality of life (QoL), regional and global systolic and diastolic function was assessed in HFNEF patients. METHODS: 150 patients with HFNEF (LVEF >45%) were randomised to (1) diuretics alone, (2) diuretics plus irbesartan, or (3) diuretics plus ramipril. QoL, 6-minute walk test (6MWT) and Doppler echocardiography were performed at baseline, 12, 24 and 52 weeks. RESULTS: The QoL score improved similarly in all three groups by 52 weeks (-46%, 51%, and 50% respectively, all p<0.01), although 6MWT increased only slightly (average +3-6%). Recurrent hospitalisation rates were equal in all groups (10-12% in 1 year). At 1 year, LV dimensions or LVEF had not changed in any group, though both systolic and diastolic blood pressures were lowered in all three groups from 4 weeks onwards. At baseline both mean peak systolic (Sm) and early diastolic (Em) mitral annulus velocities were reduced, and increased slightly in the diuretic plus irbesartan (Sm 4.5 (SEM 0.17) to 4.9 (SEM 0.16) cm/sec; Em 3.8 (SEM 0.25) to 4.2 (SEM 0.25) cm/sec) and ramipril (Sm 4.5 (SEM 0.24) to 4.9 (SEM 0.20) cm/sec; Em 3.3 (SEM 0.25) to 4.04 (SEM 0.32) cm/sec) groups (both p<0.05). NT-pro-BNP levels were raised at baseline (595 (SD 905) pg/ml; range 5-4748) and fell in the irbesartan (-124 (SD 302) pg/ml, p = 0.01) and ramipril (-173 (SD 415) pg/ml, p = 0.03) groups only. CONCLUSIONS: In this typically elderly group of HF patients with normal LVEF, diuretic therapy significantly improved symptoms and neither irbesartan nor ramipril had a significant additional effect. However, diuretics in combination with irbesartan or ramipril marginally improved LV systolic and diastolic longitudinal LV function, and lowered NT-proBNP over 1 year.
Assuntos
Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Diuréticos/uso terapêutico , Insuficiência Cardíaca Diastólica/tratamento farmacológico , Tetrazóis/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Quimioterapia Combinada , Ecocardiografia/métodos , Métodos Epidemiológicos , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca Diastólica/psicologia , Hong Kong , Humanos , Irbesartana , Masculino , Qualidade de Vida/psicologia , Ramipril/uso terapêutico , Resultado do Tratamento , Disfunção Ventricular Esquerda/psicologiaRESUMO
This paper reports theoretical probability density and cumulative distribution functions for glint and speckle target returns in a compact coherent laser radar. Calculator programs are given to facilitate use of these results.