A Violência no Local de Trabalho em Instituições de Saúde: Um Estudo Monocêntrico sobre Causas, Consequências e Estratégias de Prevenção

Introduction: Workplace violence is one of the main risk factors in the professional world. Healthcare workers are at higher risk when compared to other sectors. Our study aimed to characterize physical and verbal violence in a public hospital and to define occupational health prevention and surveillance strategies. Material and Methods: Single center observational cross-sectional study, carried amongst healthcare workers in a public hospital in Lisbon. A qualitative survey was carried out through six in-depth interviews. A quantitative survey was carried through questionnaires delivered to 32 workers. A significance level of 5% was accepted in the assessment of statistical differences. The Mann-Whitney test and the Fisher’s exact test were used to calculate p values. Results: The main results are: (1) 41 violence incidents were reported in the quantitative phase; (2) 5/21 [23.81%] victims notified the incident to the occupational health department; (3) 18/21 [85.71%] victims reported a permanent state of hypervigilance; (4) 22/28 [78.57%] participants self-reported poor or no familiarity with internal reporting procedures; (5) 24/28 [85.71%] participants believed it is possible to minimize workplace violence. Discussion: Workplace violence is favored by unrestricted access to working areas, absence of security guards and police officers or scarce intervention. The low notification rate contributes to organizational lack of action. The state of hypervigilance reported in our study reflects the negative effects of threatening occupational stressors on mental health. Conclusion: Our results show that workplace violence is a relevant risk factor that significantly impacts workers’ health in a noxious manner, deserving a tailored occupational health approach whose priority areas and strategies have been determined.Introdução: A violência no local de trabalho é um dos principais fatores de risco no mundo do trabalho. Os trabalhadores da saúde apresentam um risco superior. O nosso estudo teve como objetivo caracterizar a violência física e verbal num hospital público e definir estratégias de prevenção e vigilância em saúde ocupacional. Material e Métodos: Estudo observacional transversal monocêntrico, conduzido num hospital público em Lisboa com trabalhadores da saúde. Foi realizado um inquérito qualitativo com entrevistas em profundidade a seis trabalhadores e um inquérito quantitativo com questionários a 32 trabalhadores. Aceitou-se um nível de significância de 5% na avaliação das diferenças estatísticas. O teste de Mann-Whitney e o teste exato de Fisher foram usados para calcular os valores de p. Resultados: Os principais resultados são: (1) 41 episódios reportados na fase quantitativa; (2) 5/21 [23,81%] vítimas notificaram o incidente; (3) 18/21 [85.71%] vítimas reportaram estados de hipervigilância permanente; (4) 22/28 [78,57%] participantes não conheciam ou conheciam mal os procedimentos de notificação; (5) 24/28 [85,71%] consideravam possível minimizar o problema. Discussão: A violência é favorecida pelo acesso livre às zonas de trabalho, ausência de agentes de segurança e polícia ou falta da respetiva intervenção. A baixa notificação contribui para a ausência de medidas organizacionais. O estado de hipervigilância relatado reflete o efeito prejudicial da exposição a fontes de stress e ameaça. Conclusão: A violência no local de trabalho é um fator de risco relevante, com impacto negativo na saúde dos trabalhadores e merece uma abordagem individualizada no âmbito da saúde ocupacional, cujas áreas e estratégias prioritárias foram definidas neste estudo. Palavras-chave: Fatores de Risco Profissionais; Prevenção; Saúde Ocupacional; Trabalhadores da Saúde; Violência no Local de trabalho.info:eu-repo/semantics/publishedVersio

In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities

Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy

Legionella: Novas Abordagens, Novas Necessidades

1º Prémio na Jornada Técnica: Prevenção e Controlo da LegionellaINTRODUÇÃO: O CHLC desenvolve, desde há vários anos, procedimentos contra o crescimento e proliferação da Legionella, monitorizando e auditando as estruturas e as práticas. De acordo com as recentes orientações e normas emanadas pela DGS, surge a necessidade de criar novos instrumentos para a avaliação do risco e dar resposta às necessidades do Centro Hospitalar. OBJETIVO Identificar os fatores de risco que determinam os pontos críticos para a monitorização da Legionella. MATERIAIS E MÉTODOS: Foram construídas listas e grelhas de observação, com os fatores de risco que determinam os pontos críticos, a partir das quais se observaram as estruturas e práticas do CHLC. Os instrumentos utilizados tiveram como base os documentos publicados pela DGS, IPQ, ECDC, o procedimento multissectorial do CHLC - AMB.102 e os relatórios das auditorias. RESULTADOS: Para a avaliação das condições microbiológicas, os pontos críticos deverão ser aqueles, mais suscetíveis da ocorrência da proliferação da Legionella. Destes, a literatura salienta: Pontos distais das redes prediais Zonas de estagnação de água Idade e complexidade das redes e sistemas Sistemas e equipamentos geradores de aerossóis Após a análise dos pontos críticos foram determinados os fatores de risco que estão associados, nomeadamente: Presença de nutrientes e de biofilmes Zonas suscetíveis a fenómenos de corrosão e incrustação Origem do abastecimento de água Zonas de estagnação de água da rede predial e da água dos sistemas e equipamentos geradores de aerossóis Ausência de biocida na rede predial Tipos de materiais utilizados nas redes de canalização CONCLUSÕES A avaliação do risco permitiu reorganizar os pontos críticos definidos anteriormente e atualizar o conhecimento das condições favoráveis ao crescimento da Legionella na nossa instituição, promovendo a melhoria e atualização do programa do CHLC. Assim, torna-se evidente de que a existência de um cadastro completo e atualizado das infraestruturas, redes, sistemas e equipamentos, incluindo peças desenhadas e memórias descritivas das redes de água fria e quente, das redes dos circuitos de água de aquecimento e arrefecimento e uso terapêutico, é essencial para que a avaliação do risco seja mais proficiente.info:eu-repo/semantics/publishedVersio

The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour

BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy

Attenuation of muscle atrophy by an N-terminal peptide of the receptor for proteolysis-inducing factor (PIF)

Background: Atrophy of skeletal muscle in cancer cachexia has been attributed to a tumour-produced highly glycosylated peptide called proteolysis-inducing factor (PIF). The action of PIF is mediated through a high-affinity membrane receptor in muscle. This study investigates the ability of peptides derived from the 20 N-terminal amino acids of the receptor to neutralise PIF action both in vitro and in vivo. Methods: Proteolysis-inducing factor was purified from the MAC16 tumour using an initial pronase digestion, followed by binding on DEAE cellulose, and the pronase was inactivated by heating to 80°C, before purification of the PIF using affinity chromatography. In vitro studies were carried out using C2C12 murine myotubes, while in vivo studies employed mice bearing the cachexia-inducing MAC16 tumour. Results: The process resulted in almost a 23?000-fold purification of PIF, but with a recovery of only 0.004%. Both the D- and L-forms of the 20mer peptide attenuated PIF-induced protein degradation in vitro through the ubiquitin-proteosome proteolytic pathway and increased expression of myosin. In vivo studies showed that neither the D- nor the L-peptides significantly attenuated weight loss, although the D-peptide did show a tendency to increase lean body mass. Conclusion: These results suggest that the peptides may be too hydrophilic to be used as therapeutic agents, but confirm the importance of the receptor in the action of the PIF on muscle protein degradation

Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy

Gastro-oesophageal cancer is associated with a high incidence of cachexia. Proteolysis-inducing factor (PIF) has been identified as a possible cachectic factor and studies suggest that PIF is produced exclusively by tumour cells. We investigated PIF core peptide (PIF-CP) mRNA expression in tumour and benign tissue from patients with gastro-oesophageal cancer and in gastro-oesophageal biopsies for healthy volunteers. Tumour tissue and adjacent benign tissue were collected from patients with gastric and oesophageal cancer (n=46) and from benign tissue only in healthy controls (n=11). Expression of PIF-CP mRNA was quantified by real-time PCR. Clinical and pathological information along with nutritional status was collected prospectively. In the cancer patients, PIF-CP mRNA was detected in 27 (59%) tumour samples and 31 (67%) adjacent benign tissue samples. Four (36%) gastro-oesophageal biopsies from healthy controls also expressed PIF-CP mRNA. Expression was higher in tumour tissue (P=0.031) and benign tissue (P=0.022) from cancer patients compared with healthy controls. In the cancer patients, tumour and adjacent benign tissue PIF-CP mRNA concentrations were correlated with each other (P<0.0001, r=0.73) but did not correlate with weight loss or prognosis. Although PIF-CP mRNA expression is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy, expression does not relate to prognosis or cachexia. Post-translational modification of PIF may be a key step in determining the biological role of PIF in the patient with advanced cancer and cachexia

Increased expression of the ubiquitin – proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-κB

Proteolysis-inducing factor (PIF), isolated from a cachexia-inducing murine tumour, has been shown to stimulate protein breakdown in C 2C12 myotubes. The effect was attenuated by the specific proteasome inhibitor lactacystin and there was an elevation of proteasome 'chymotrypsin-like' enzyme activity and expression of 205 proteasome α-subunits at concentrations of PIF between 2 and 16 nM. Higher concentrations of PIF had no effect. The action of PIF was attenuated by eicosapentaenoic acid (EPA) (50 μM). At a concentration of 4 nM, PIF induced a transient decrease in IκBα levels after 30 min incubation, while no effect was seen at 20 nM PIF. The level of IκBα, an NF-κB inhibitory protein, returned to normal after 60 min. Depletion of IκBα from the cytosol was not seen in myotubes pretreated with EPA, suggesting that the NF-κB/IκB complex was stabilised. At concentrations between 2 and 8 nM, PIF stimulated an increased nuclear migration of NF-κB, which was not seen in myotubes pretreated with EPA. The PIF-induced increase in chymotrypsin-like enzyme activity was also attenuated by the NF-κB inhibitor peptide SN50, suggesting that NF-κB may be involved in the PIF-induced increase in proteasome expression. The results further suggest that EPA may attenuate protein degradation induced by PIF, at least partly, by preventing NF-κB accumulation in the nucleus. © 2003 Cancer Research UK

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

BACKGROUND: Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. METHODS: In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. RESULTS: WF decreased the viability of C2C12 myotubes, especially at concentrations of 20-25 mug.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. CONCLUSION: These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model. © 2008 Yano et al; licensee BioMed Central Ltd

Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia can findings from animal models be translated to humans?

Background: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. Discussion: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. Summary: More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future

The Risk of Exposure to Ionizing Radiation During Endovascular Procedures

Objectivos: Com a generalização dos procedimentos endovasculares, cresce a preocupação com os efeitos deletérios que a execução continuada de tais procedimentos radiológicos acarreta. Com este trabalho pretendeu-se avaliar e quantificar a distribuição pela equipa cirúrgica da exposição à radiação dispersa, emitida por um aparelho portátil de radioscopia com arco cirúrgico (arco em C), durante a utilização em bloco operatório. Material e métodos: O registo e avaliação da dose de radiação foram efectuados em sala do bloco operatório reproduzindo as condições habituais em que decorrem os procedimentos endovasculares. Para a simulação geométrica do tórax do doente foi utilizado um fantoma cilíndrico de polimetilmetacrilato (PMMA) com 15 cm de espessura. A radiação dispersa foi medida para o local do cirurgião, ajudante, anestesista e enfermeira instrumentista, através de um monitor de radiação portátil RaySafe Xi Survey Detector, tendo sido ajustada a medição para a avaliação da taxa de dose de exposição à radiação em mGy/s a diversas alturas do solo e distâncias do doente. Utilizou-se ainda o detetor RaySafe Xi R/F para a medição da taxa de dose de exposição na superfície de entrada da pele do doente. As medições foram efectuadas em modo de fl uoroscopia pulsada de 4 quadros por segundo (qps), subtração digital e roadmap, com a combinação dos três modos de magnifi cação electrónica disponíveis (Mag1, Mag2 e Mag3). Em todos os casos foi considerada a Dose 3, o nível de dose máxima do aparelho que fornece a melhor qualidade de imagem através do controlo automático em tempo real do contraste e do brilho. Resultados: A análise dos dados permitiu determinar a distribuição da radiação dispersa pela equipa assistente, constatando-se como nível máximo de exposição, a altura ao solo de 120 cm no modo de subtracção digital e roadmap. A este nível, a intensidade da radiação dispersa em relação à taxa de dose de exposição na superfície de entrada da pele do doente é distribuída em 0,47% pelo cirurgião, 0,21% pelo anestesista, 0,32% pelo ajudante e 0,13% pela enfermeira instrumentista. A utilização de subtração digital e roadmap aumentou o nível de radiação cerca de 5 vezes em relação à fluoroscopia pulsada a 4 qps, tanto na taxa de dose de exposição na superfície de entrada da pele do doente como na radiação dispersa pela equipa. Quando utilizados os meios de proteção radiológica os níveis de radiação foram consideravelmente inferiores. Conclusões: Atendendo à dispersão prevista da radiação determinou-se que a proximidade da ampola aumenta a quantidade de radiação dispersa que atinge o corpo. Quando utilizado o equipamento de proteção individual, os níveis de radiação dispersa são consideravelmente menores e permitem doses acumuladas abaixo dos limites aceitáveis