RESUMEN

The metallic interface between insulating LaAlO3 and SrTiO3 opens up the field of oxide electronics. With more than a decade of researches on this heterostructure, the origin of the interfacial conductivity, however, remains unsettled. Here we resolve this long-standing puzzle by atomic-scale observation of electron-gas formation for screening hidden lattice instabilities, rejuvenated near the interface by epitaxial strain. Using atomic-resolution imaging and electron spectroscopy, the generally accepted notions of polar catastrophe and cation intermixing for the metallic interface are discounted. Instead, the conductivity onset at the critical thickness of 4-unit cell LaAlO3 on SrTiO3 substrate is accompanied with head-to-head ferroelectric-like polarizations across the interface due to strain-rejuvenated ferroelectric-like instabilities in the materials. The divergent depolarization fields of the head-to-head polarizations cast the interface into an electron reservoir, forming screening electron gas in SrTiO3 with LaAlO3 hosting complementary localized holes. The ferroelectric-like polarizations and electron-hole juxtaposition reveal the cooperative nature of metallic LaAlO3/SrTiO3.

RESUMEN

The involvement of the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway in cancer cell survival is poorly understood. Here we show that the NAD(+) salvage pathway modulates cancer cell survival through the rarely mutated tumour suppressor p73. Our data show that pharmacological inhibition or knockdown of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD(+) salvage pathway, enhances autophagy and decreases survival of cancer cells in a p53-independent manner. Such NAMPT inhibition stabilizes p73 independently of p53 through increased acetylation and decreased ubiquitination, resulting in enhanced autophagy and cell death. These effects of NAMPT inhibition can be effectively reversed using nicotinamide mononucleotide (NMN), the enzymatic product of NAMPT. Similarly, knockdown of p73 also decreases NAMPT inhibition-induced autophagy and cell death, whereas overexpression of p73 alone enhances these effects. We show that the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) harbour significantly higher levels of NAMPT and lower levels of p73 than does the normal cell line (MCF-10A), and that NAMPT inhibition is cytotoxic exclusively to the cancer cells. Furthermore, data from 176 breast cancer patients demonstrate that higher levels of NAMPT and lower levels of p73 correlate with poorer patient survival, and that high-grade tumours have significantly higher NAMPT/p73 mRNA ratios. Therefore, the inverse relationship between NAMPT and p73 demonstrable in vitro is also reflected from the clinical data. Taken together, our studies reveal a new NAMPT-p73 nexus that likely has important implications for cancer diagnosis, prognosis and treatment.

Asunto(s)

Autofagia , Citocinas/metabolismo , NAD/metabolismo , Neoplasias/metabolismo , Nicotinamida Fosforribosiltransferasa/metabolismo , Proteína Tumoral p73/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Supervivencia Celular , Citocinas/genética , Humanos , Células Jurkat , Células MCF-7 , NAD/genética , Neoplasias/genética , Neoplasias/mortalidad , Neoplasias/patología , Nicotinamida Fosforribosiltransferasa/genética , Proteína Tumoral p73/genética , Proteína p53 Supresora de Tumor/genética

RESUMEN

Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus release through apoptosis; however, the mechanism behind the latter is not well understood. Here, we show that reovirus alters the intracellular location of oncogenic Ras to induce apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation, treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose-dependent increase in progeny virus release and subsequent spread. Conversely, tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the Golgi) allows for efficient virus production, but results in basal levels of reovirus-induced cell death. Analysis of Ras downstream signaling reveals that cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c-Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases activation of the MEKK1/MKK4/JNK signaling pathway to promote cell death. Collectively, our data suggest that reovirus induces Golgi fragmentation of target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body initiates apoptotic signaling events required for virus release and spread.

Asunto(s)

Apoptosis , Proteína Oncogénica p21(ras)/metabolismo , Virus Oncolíticos/fisiología , Reoviridae/fisiología , Liberación del Virus , Animales , Transformación Celular Neoplásica/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Ratones , Células 3T3 NIH , Viroterapia Oncolítica , Transporte de Proteínas , Transducción de Señal , Replicación Viral

RESUMEN

Multiple sclerosis (MS) is an immune-mediated chronic central nervous system (CNS) disease affecting more than 400 000 people in the United States. Myelin-reactive CD4 T cells play critical roles in the formation of acute inflammatory lesions and disease progression in MS and experimental autoimmune encephalomyelitis (EAE), a well-defined mouse model for MS. Current MS therapies are only partially effective, making it necessary to develop more effective therapies that specifically target pathogenic myelin-specific CD4 T cells for MS treatment. While suppressing T-bet, the key transcription factor in T helper type 1 (Th1) cells, has been demonstrated to be beneficial in prevention and treatment of EAE, the therapeutic potential of retinoic acid-related orphan receptor gamma t (ROR)γt, the key transcription factor for Th17 cells, has not been well-characterized. In this study, we characterized the correlation between RORγt expression and other factors affecting T cell encephalitogenicity and evaluated the therapeutic potential of targeting RORγt by siRNA inhibition of RORγt. Our data showed that RORγt expression correlates with interleukin (IL)-17 production, but not with the encephalitogenicity of myelin-specific CD4 T cells. IL-23, a cytokine that enhances encephalitogenicity, does not enhance RORγt expression significantly. Additionally, granulocyte-macrophage colony-stimulating factor (GM-CSF) levels, which correlate with the encephalitogenicity of different myelin-specific CD4 T cell populations, do not correlate with RORγt. More importantly, inhibiting RORγt expression in myelin-specific CD4 T cells with an siRNA does not reduce disease severity significantly in adoptively transferred EAE. Thus, RORγt is unlikely to be a more effective therapeutic target for ameliorating pathogenicity of encephalitogenic CD4 T cells.

Asunto(s)

Sistema Nervioso Central/inmunología , Sistema Nervioso Central/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/inmunología , Expresión Génica , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Interleucina-23/metabolismo , Interleucina-23/farmacología , Ratones , Ratones Noqueados , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Vaina de Mielina/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Interferencia de ARN

RESUMEN

Class I mismatched kidney transplantation in Massachusetts General Hospital MHC-defined miniature swine has been studied extensively as a model for induction of systemic allograft tolerance. In a large series of juvenile swine, long-term graft acceptance has been observed consistently following a 12-day course of cyclosporine. It was therefore surprising when three of five recipients in one of our studies rejected their grafts. Examination of the origins of the rejecting animals revealed that they were derived from a subline of the SLA(dd) miniature swine herd that was intentionally being inbred toward full homozygosity and had been inbred for eight generations prior to these experiments. A blinded study of additional class I mismatched renal transplants into animals from this subline confirmed the genetic basis of this rejection. We present here preliminary evidence suggesting that a likely explanation for this phenomenon is that the rejectors in this subline are homozygous for a recessive mutant allele of a gene normally involved in the induction of tolerance. Subsequent studies will be directed toward identification and characterization of the gene(s) involved, since existence of a similar genetic locus in humans might have implications for assessing an individual's likelihood of graft rejection versus tolerance induction prior to organ transplantation.

Asunto(s)

Ciclosporina/uso terapéutico , Rechazo de Injerto/diagnóstico , Antígenos de Histocompatibilidad Clase II/genética , Enfermedades Renales/complicaciones , Trasplante de Riñón/efectos adversos , Tolerancia al Trasplante/genética , Animales , Terapia Combinada , Rechazo de Injerto/etiología , Antígenos de Histocompatibilidad Clase I , Inmunosupresores/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/cirugía , Porcinos , Porcinos Enanos , Tolerancia al Trasplante/efectos de los fármacos

RESUMEN

BACKGROUND: Reovirus preferentially infects and kills cancer cells and is currently undergoing clinical trials internationally. While oncolysis is the primary mode of tumour elimination, increasing evidence illustrates that reovirus additionally stimulates anti-tumour immunity with a capacity to target existing and possibly relapsing cancer cells. These virus-induced anti-tumour immune activities largely determine the efficacy of oncotherapy. On the other hand, anti-viral immune responses can negatively affect oncotherapy. Hence, the strategic management of anti-tumour and anti-viral immune responses through complementary therapeutics is crucial to achieve the maximum anti-cancer benefits of oncotherapy. METHODS: Intra-peritoneal injection of mouse ovarian surface epithelial cells (ID8 cells) into wild-type C57BL/6 mice was treated with a therapeutic regimen of reovirus and/or gemcitabine and then analysed for prolonged survival, disease pathology, and various immunological parameters. Furthermore, in vitro analyses were conducted to assess apoptosis, viral spread, and viral production during reovirus and/or gemcitabine treatment. RESULTS: We demonstrate that reovirus and gemcitabine combination treatment postpones peritoneal carcinomatosis development and prolongs the survival of cancer-bearing hosts. Importantly, these anti-cancer benefits are generated through various immunological mechanisms, including: (1) inhibition of myeloid-derived suppressor cells recruitment to the tumour microenvironment, (2) downmodulation of pro-MDSC factors, and (3) accelerated development of anti-tumour T-cell responses. CONCLUSION: The complementation of reovirus with gemcitabine further potentiates virus-initiated anti-cancer immunity and enhances the efficacy of oncotherapy. In the context of ongoing clinical trials, our findings represent clinically relevant information capable of enhancing cancer outcomes.

Asunto(s)

Desoxicitidina/análogos & derivados , Viroterapia Oncolítica/métodos , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Reoviridae/fisiología , Animales , Antimetabolitos Antineoplásicos/farmacología , Línea Celular Tumoral , Terapia Combinada , Desoxicitidina/farmacología , Femenino , Ratones , Ratones Endogámicos C57BL , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/virología , Reoviridae/inmunología , Linfocitos T/inmunología , Replicación Viral/efectos de los fármacos , Gemcitabina

RESUMEN

"Functional" amyloids are found throughout nature as robust materials. We have discovered that "template" and "adder" proteins cooperatively self-assemble into micrometer-sized amyloid fibers with a controllable, hierarchical structure. Here, Escherichia coli is genetically engineered to express a template protein, Gd20, that can initiate self-assembly of large amyloid fibrils and fibers. Through atomic force microscopy (AFM) we found that expression of Gd20 produces large amyloid fibrils of 490 nm diameter and 2-15 µm length. Addition of an extracellular adder protein, myoglobin, continues self-assembly to form amyloid tapes with widths of ∼7.5 µm, heights of ∼400 nm, and lengths exceeding 100 µm. Without myoglobin the amyloid fibrils are metastable over time. When myoglobin is present, the amyloid fiber continues self-assembling to a width of ∼18 µm and height of ∼1 µm. Experimental results demonstrate that large amyloid fibers with a tailored stiffness and morphology can be engineered at the DNA level, spanning four orders of magnitude.

RESUMEN

Gemcitabine is a chemotherapeutic that is widely used for the treatment of a variety of haematological malignancies and has become the standard chemotherapy for the treatment of advanced pancreatic cancer. Combinational gemcitabine regimes (e.g.with doxorubicin) are being tested in clinical trials to treat a variety of cancers, including colon cancer. The limited success of these trials has prompted us to pursue a better understanding of gemcitabine's mechanism of cell killing, which could dramatically improve the therapeutic potential of this agent. For comparison, we included gamma irradiation that triggers robust cell cycle arrest and Cr(VI), which is a highly toxic chemical that induces a robust p53-dependent apoptotic response. Gemcitabine induced a potent p53-dependent apoptosis that correlated with the accumulation of pro-apoptotic proteins such as PUMA and Bax. This is accompanied by a drastic reduction in p2l and 14-3-3σ protein levels, thereby significantly sensitizing the cells to apoptosis. In vitro and in vivo studies demonstrated that gemcitabine required PUMA transcription to instigate an apoptotic programme. This was in contrast to Cr(VI)-induced apoptosis that required Bax and was independent of transcription. An examination of clinical colon and pancreatic cancer tissues shows higher p53, p21, 14-3-3σ and Bax expression compared with matched normal tissues, yet there is a near absence of PUMA protein. This may explain why gemcitabine shows only limited efficacy in the treatment of these cancers. Our results raise the possibility that targeting the Bax-dependent cell death pathway, rather than the PUMA pathway, could result in significantly improved patient outcome and prognosis for these cancers.

Asunto(s)

Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas 14-3-3/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Cromo/farmacología , Cromo/uso terapéutico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Daño del ADN , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones SCID , Modelos Biológicos , Biosíntesis de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Inducción de Remisión , Transcripción Genética/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Gemcitabina

RESUMEN

The major allergen parvalbumin was purified from cod muscle tissues, and polyclonal antibodies were raised towards it. The antibodies were tested for specificity and an enzyme-linked immunosorbent assay (ELISA) was developed using these antibodies. The ELISA was applied to measure parvalbumin in cod skin, the starting material for fish gelatin made from deep sea, wild fish. The ELISA was sufficiently sensitive (LLOQ = 0.8 ng ml(-1) in extracts, corresponding to 0.02 µg of parvalbumin per g of tissue), and did not cross-react with common food constituents. Fish gelatin, wine and beer, matrices for the potential use of this ELISA, did not cause disturbance of the assay performance. The data show that the parvalbumin content in cod muscle tissue is 6.25 mg g(-1), while the skins contained considerably less, 0.4 mg g(-1). Washing of the skins, a common industrial procedure during the manufacturing of fish gelatin, reduced the level of parvalbumin about 1000-fold to 0.5 µg g(-1), or 0.5 ppm. From 95 commercial lots of fish gelatin it is shown that 73 are below 0.02 µg g(-1) parvalbumin. From the other 22 lots, the one with the highest concentration contained 0.15 µg g(-1) of parvalbumin. These levels are generally assumed to be safe for fish-allergic individuals.

Asunto(s)

Alérgenos/análisis , Hipersensibilidad a los Alimentos/etiología , Gadus morhua/inmunología , Gelatina/efectos adversos , Parvalbúminas/análisis , Alérgenos/inmunología , Animales , Especificidad de Anticuerpos , Calibración , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Gelatina/análisis , Humanos , Límite de Detección , Parvalbúminas/inmunología

RESUMEN

BACKGROUND: Naturally oncolytic reovirus preferentially kills cancer cells, making it a promising cancer therapeutic. Mutations in tumour suppressor p53 are prevalent in cancers, yet the role of p53 in reovirus oncolysis is relatively unexplored. METHODS: Human cancer cell lines were exposed to Nutlin-3a, reovirus or a combination of the two and cells were processed for reovirus titration, western blot, real-time PCR and apoptosis assay using Annexin V and 7-AAD staining. Confocal microscopy was used to determine translocation of the NF-κB p65 subunit. RESULTS: We show that despite similar reovirus replication in p53(+/+) and p53(-/-) cells, stabilisation of p53 by Nutlin-3a significantly enhanced reovirus-induced apoptosis and hence virus release and dissemination while having no direct effect on virus replication. Enhanced apoptosis by Nutlin-3a was not observed in p53(-/-) or p53 knockdown cells; however, increased expression of Bax and p21 are required. Moreover, elevated NF-κB activation in reovirus-infected cells following Nutlin-3a treatment was necessary for enhanced reovirus-induced apoptosis, as synergistic cytotoxicity was overcome by specific NF-κB inhibitors. CONCLUSION: Nutlin-3a treatment enhances reovirus-induced apoptosis and virus spread through p53-dependent NF-κB activation, and combination of reovirus and Nutlin-3a might represent an improved therapy against cancers harbouring wild-type p53.

Asunto(s)

Apoptosis , Mutación/genética , FN-kappa B/metabolismo , Reoviridae/fisiología , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/metabolismo , Western Blotting , Ciclo Celular , Línea Celular Tumoral , Núcleo Celular , Proliferación Celular , Humanos , Imidazoles/farmacología , Técnicas para Inmunoenzimas , Luciferasas/metabolismo , FN-kappa B/genética , Piperazinas/farmacología , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína p53 Supresora de Tumor/genética

RESUMEN

AIM: The aim was to explore emotional distress and health risk behaviours of mothers of servicemen. The study was inspired by the first author's clinical practice in primary care among women who reported significant emotional distress surrounding impending deployment of their sons. BACKGROUND: Thousands of US service members have been deployed in the current wars. The potentially profound effects of deployment on emotional distress of military spouses and children have been documented; however, mothers of servicemen have not been studied. METHODS: This was an exploratory descriptive study to determine self-reported levels of emotional distress and health risk behaviours in the mothers of deployed male US Marines compared with mothers of male Marines not currently deployed. Mothers were accessed via a voluntary online support organization. RESULTS: Mothers of deployed sons reported significantly higher levels of emotional distress and more health risk behaviours compared with mothers of sons not deployed. Many of the mothers in both groups reported high levels of emotional distress. DISCUSSION: As primary care providers, nurses should be alert to the high levels of emotional distress and health risk behaviours among all patients. This exploratory study highlights these dimensions in mothers of servicemen. CONCLUSIONS: This study is the first of mothers of sons serving in the military. While the focus is on mothers of sons serving in the US military, their experience is likely not unique. Mothers of military service members all over the world send their children off to war and wait for their safe return.

Asunto(s)

Campaña Afgana 2001- , Conductas Relacionadas con la Salud , Guerra de Irak 2003-2011 , Personal Militar , Madres/psicología , Estrés Psicológico , Adulto , Consumo de Bebidas Alcohólicas , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asunción de Riesgos , Factores Socioeconómicos , Estados Unidos , Adulto Joven

RESUMEN

BACKGROUND: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. METHODS: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. RESULTS: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated σ1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. CONCLUSION: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy.

Asunto(s)

Viroterapia Oncolítica , Reoviridae/patogenicidad , Animales , Secuencia de Bases , Western Blotting , Línea Celular , Cartilla de ADN , Humanos , Inmunohistoquímica , Ratones , Ratones SCID , Microscopía Electrónica , Biosíntesis de Proteínas , Reoviridae/genética , Transcripción Genética , Trasplante Heterólogo , Virulencia

RESUMEN

Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

Asunto(s)

Genes Supresores de Tumor , Myxoma virus/fisiología , Neoplasias/genética , Neoplasias/virología , Virus Oncolíticos/fisiología , Reoviridae/fisiología , Tropismo Viral , Animales , Apoptosis/genética , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Eliminación de Gen , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Neoplasias/patología , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Proteína de Retinoblastoma/deficiencia , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genética

RESUMEN

CONTEXT: The World Alliance for Patient Safety was formed to accelerate worldwide research progress towards measurably improving patient safety. Although rates of adverse events have been studied in industrialised countries, little is known about the rates of adverse events in developing and emerging countries. PURPOSE: To review the literature on patient safety issues in developing and emerging countries, to identify patient safety measures presently used in these countries and to propose a method of measurably improving patient safety measurement in these countries. METHODS: Using the Medline database for 1998 to 2007, we identified and reviewed 23 English-language articles that examined patient safety measurement in developing and emerging countries. Results Our review included 12 studies that prospectively measured patient safety and 11 studies that retrospectively measured safety. Two studies used measures of structure and the remaining used process measures, outcome measures or both. Whereas a few studies used surveys or direct observation, most studies used chart audits to measure patient safety. Most studies addressed safety at a single facility. CONCLUSIONS: Investigation of patient safety in developing and emerging countries has been infrequent and limited in scope. Establishing fundamental safe patient practices, integrating those processes into routine health services delivery and developing patients' expectations that such processes be present are necessary prerequisites to measuring and monitoring progress towards safe patient care in emerging and developing countries.

Asunto(s)

Países en Desarrollo , Seguridad del Paciente/normas , Garantía de la Calidad de Atención de Salud , Administración de la Seguridad/normas , Salud Global , Humanos

Asunto(s)

Reoviridae/fisiología , Replicación Viral/fisiología , Proteínas ras/fisiología , Humanos , Reoviridae/genética , Transducción de Señal

RESUMEN

OBJECTIVE: To explore Chinese women's perceptions of human papillomavirus (HPV) vaccination and their intention to be vaccinated. DESIGN: A cross-sectional community-based survey study. SETTING: Thirteen community women's health centres of The Family Planning Association of Hong Kong. SAMPLE: A total of 1450 ethnic Chinese women aged 18 or above who attended the health centres. METHODS: Participants completed a written consent and an anonymous questionnaire onsite. MAIN OUTCOME MEASURES: Knowledge and beliefs about HPV and HPV vaccination against cervical cancer and participants' own intention to be vaccinated. RESULTS: About 38% of the participants (n = 527) had heard of HPV and 50% (n = 697) had heard of vaccination against cervical cancer. HPV infection was perceived to be stigmatising and detrimental to intimate, family and social relationships. Despite misconceptions and a grossly inadequate knowledge about HPV and HPV vaccination, 88% of the participants (n = 1219) indicated that they would likely be vaccinated. Majority of the participants believed that sexually experienced women should be vaccinated, while 27% opposed vaccinating sexually naive women. Younger age women who perceived a disruptive impact of HPV infection on intimate relationship and their partners' approval were significantly associated with a positive intention to be HPV vaccinated. CONCLUSIONS: The easy acceptability of HPV vaccination among the mostly sexually experienced Chinese participants and their knowledge deficit on the subject may implicate potential misuse of the vaccines and a false sense of security against cervical cancer. There is a dire need for culturally sensitive and tailored education for the public, women of different ages and their partners about HPV and HPV vaccination. Emphasis must be placed on the prophylactic nature of the current vaccines, the uncertain effects when given to sexually experienced women, the importance of adolescent vaccination and the need for continued cervical screening whether vaccinated or not.

Asunto(s)

Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Satisfacción del Paciente/etnología , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Hong Kong/epidemiología , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/etnología , Infecciones por Papillomavirus/psicología , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/etnología , Adulto Joven

RESUMEN

Undeclared mustard residues in food products could trigger allergic reactions in mustard-allergic consumers. Our objective was to develop and validate a sandwich-type ELISA for the detection of mustard residues in foods. A mixture of yellow, brown, and oriental mustard seeds was used to immunize 3 rabbits and 1 sheep. Two mustard ELISAs were developed by utilizing the reciprocal combination of rabbit and sheep polyclonal antimustard sera as the capture and detector reagents. Binding was visualized by addition of rabbit antisheep or goat antirabbit IgG antibody labeled with alkaline phosphatase and subsequent addition of substrate. The optimized ELISAs have limits of quantification (LOQ) of 1 and 3 ppm (mug of ground, whole mustard seeds/mL) for the sheep capture and rabbit capture formats, respectively. Only rapeseed cross-reacted in the rabbit and sheep capture mustard ELISAs at a level equivalent to 12300 and 16900 ppm of mustard. The mean percent recovery for cooked frankfurters spiked with 0 to 1000 ppm mustard flour was 95.3%+/- 10.7%. A limited retail survey of 29 foods revealed that, of 15 samples having mustard declared on the ingredient list, 2 baked bean products contained no detectable mustard, possibly owing to a decrease in extractability and detectability of mustard proteins after subjecting to thermal processing. For the remaining 14 samples without mustard declared on the label, 3 samples contained detectable mustard, presumably due to the labeling of mustard as "spice" or inadvertent cross-contamination. This sandwich-type ELISA can serve as a powerful tool for food manufacturers and regulatory agencies to detect and quantify mustard residues in processed foods.

Asunto(s)

Ensayo de Inmunoadsorción Enzimática/métodos , Análisis de los Alimentos , Planta de la Mostaza/química , Alérgenos/análisis , Animales , Especificidad de Anticuerpos , Hipersensibilidad a los Alimentos/prevención & control , Sueros Inmunes/biosíntesis , Sueros Inmunes/inmunología , Inmunización , Indicadores y Reactivos , Productos de la Carne/análisis , Planta de la Mostaza/inmunología , Conejos/inmunología , Semillas/química , Semillas/inmunología , Ovinos/inmunología

RESUMEN

OBJECTIVES: To explore perceptions towards cervical cancer, human papillomavirus (HPV) infection and HPV vaccination and to identify factors affecting the acceptability of HPV vaccination among Chinese adolescent girls in Hong Kong. METHODS: Six focus groups were conducted with Chinese adolescent girls (median age 16 years, age range 13-20, n = 64) in Hong Kong in April 2007. Thematic analysis was employed to identify major themes related to cervical cancer and HPV vaccination. A supplementary questionnaire was administered to all participants before and after group discussion to assess their knowledge, attitudes and intention to be vaccinated and to collect demographic information. RESULTS: Participants' knowledge on cervical cancer was limited and HPV was largely unheard of. They had difficulty understanding the mechanism linking cervical cancer with HPV infection. Participants held a favourable attitude towards HPV vaccination but the perceived timing of vaccination varied. Barriers to vaccination include high monetary cost, uncertain length of vaccine effectiveness, low perceived risk of HPV infection, no immediate perceived need of vaccination, anticipated family disapproval and fear of the pain of injection. Factors conducive to vaccination include perceived family and peer support and medical reassurance on safety and efficacy of vaccine. The differences on knowledge, attitudes, intention to be vaccinated now and willingness to conform to significant others before and after the discussion were statistically significant, with an increased tendency towards favouring vaccination after the focus group. CONCLUSIONS: Participants favoured HPV vaccination despite not feeling an immediate need to be vaccinated. Interventions could focus on providing professional information on HPV vaccination and raising adolescents' perceived need to take preventive measures against HPV infection.

Asunto(s)

Pueblo Asiatico/etnología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Aceptación de la Atención de Salud/etnología , Adolescente , Adulto , Femenino , Grupos Focales , Hong Kong/epidemiología , Humanos , Infecciones por Papillomavirus/etnología , Neoplasias del Cuello Uterino/psicología

RESUMEN

A postal survey was sent to anaesthetic trainees in Hong Kong and Victoria, Australia to compare work-related stress levels. Demographic data were collected. Anaesthetist-specific stressors, Maslach Burnout Inventory and Global Job Satisfaction scores were used for psychological testing. The response rates from Hong Kong and Melbourne were 64 of 133 (48.1%) and 108 of 196 (55.1%), respectively. Victorian respondents were older with greater family commitments, but more advanced in fulfilling training requirements. Hong Kong respondents, being faced with both the challenge of dual College requirements, exhibited consistently higher indices of stress (P < 0.001) and less job satisfaction (P < 0.001). Common occupational stressors related to dealing with critically ill patients and medicolegal concerns. Higher stress scores observed in Hong Kong trainees related to service provision and a perceived lack of resources. Despite the complex nature of stress, its antecedents and manifestations, an inverse relationship between emotional exhaustion and job satisfaction was evident in correlation analysis (P < 0.001). This survey suggests that stress was present in some trainees in both areas. Hong Kong trainees may benefit from local development to address mental wellbeing as being important to fulfil this highly competitive training program.

Asunto(s)

Anestesiología/educación , Anestesiología/estadística & datos numéricos , Agotamiento Profesional/epidemiología , Encuestas de Atención de la Salud/estadística & datos numéricos , Satisfacción en el Trabajo , Estrés Psicológico/epidemiología , Adulto , Distribución por Edad , Agotamiento Profesional/psicología , Educación de Postgrado en Medicina/estadística & datos numéricos , Familia/psicología , Femenino , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Victoria/epidemiología

RESUMEN

BACKGROUND: Psychological morbidity is commonly found in medical students. AIMS: The Mental Health Support Group (MSG), a student-initiated and student-run web-based peer support service aims to provide mental health information, e mail counseling and an online forum for medical students. METHODS: The development process of MSG is described in the paper with presentation of preliminary evaluation results. RESULTS: Preliminary evaluation shows promising results. Student members of MSG acquired valuable skills in counseling, communication, webpage design and maintenance of an online forum. CONCLUSIONS: Future challenges include succession issues, strategies to keep up the momentum, enhancement of publicity and further diversification of service to meet the needs of our students.

Asunto(s)

Información de Salud al Consumidor/métodos , Promoción de la Salud/métodos , Salud Mental , Estudiantes de Medicina/psicología , Información de Salud al Consumidor/tendencias , Femenino , Hong Kong , Humanos , Internet , Masculino , Trastornos Mentales/psicología , Grupo Paritario , Evaluación de Programas y Proyectos de Salud , Factores Sexuales , Apoyo Social , Estrés Psicológico/psicología , Encuestas y Cuestionarios