Social, economic, and health impact of the respiratory syncytial virus: a systematic search

Background: Bronchiolitis caused by the respiratory syncytial virus (RSV) and its related complications are common in infants born prematurely, with severe congenital heart disease, or bronchopulmonary dysplasia, as well as in immunosuppressed infants. There is a rich literature on the different aspects of RSV infection with a focus, for the most part, on specific risk populations. However, there is a need for a systematic global analysis of the impact of RSV infection in terms of use of resources and health impact on both children and adults. With this aim, we performed a systematic search of scientific evidence on the social, economic, and health impact of RSV infection. Methods: A systematic search of the following databases was performed: MEDLINE, EMBASE, Spanish Medical Index, MEDES-MEDicina in Spanish, Cochrane Plus Library, and Google without time limits. We selected 421 abstracts based on the 6,598 articles identified. From these abstracts, 4 RSV experts selected the most relevant articles. They selected 65 articles. After reading the full articles, 23 of their references were also selected. Finally, one more article found through a literature information alert system was included. Results: The information collected was summarized and organized into the following topics: 1. Impact on health (infections and respiratory complications, mid-to long-term lung function decline, recurrent wheezing, asthma, other complications such as otitis and rhino-conjunctivitis, and mortality; 2. Impact on resources (visits to primary care and specialists offices, emergency room visits, hospital admissions, ICU admissions, diagnostic tests, and treatments); 3. Impact on costs (direct and indirect costs); 4. Impact on quality of life; and 5. Strategies to reduce the impact (interventions on social and hygienic factors and prophylactic treatments). Conclusions: We concluded that 1. The health impact of RSV infection is relevant and goes beyond the acute episode phase; 2. The health impact of RSV infection on children is much better documented than the impact on adults; 3. Further research is needed on mid-and long-term impact of RSV infection on the adult population, especially those at high-risk; 4. There is a need for interventions aimed at reducing the impact of RSV infection by targeting health education, information, and prophylaxis in high-risk populations.

In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. Methods: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4-7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. Results: The nebulization system produced relatively large amounts of aerosol ranging between 0.3 +/- 0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0 +/- 0.1 ml/min for distilled water (H(2)Od) at 6 bar, with MMADs between 2.61 +/- 0.1 mu m for PFD at 7 bar and 10.18 +/- 0.4 mu m for FC-75 at 6 bar. The deposition study showed that for surfactant and H(2)Od aerosols, the highest percentage of the aerosolized mass (similar to 65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH(2)O only increased total airway pressure by 1.59 cmH(2)O at the highest driving pressure (7 bar). Conclusion: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

Fatores de risco para ocorrência de restrição do crescimento extra-uterino em prematuros de muito baixo peso ao nascer

A desnutrição em recém-nascidos prematuros de muito baixo peso ao nascer (MBPN) é um fenômeno universal e vem aumentando nas últimas décadas. A restrição do crescimento extra-uterino (RCEU) é um importante indicador do estado nutricional nestes pacientes. O objetivo deste estudo foi identificar os fatores de risco para RCEU durante a internação hospitalar. Foi realizado estudo de coorte retrospectiva que incluiu 188 recém-nascidos MBPN adequados para idade gestacional (AIG), no período de 2002 a 2004. A análise constituiu-se em um modelo de regressão linear longitudinal de efeitos mistos, sendo observada a diferença na taxa de variação do peso para crianças com e sem RCEU na alta hospitalar. Oitenta e sete (46%) dos recém-nascidos incluídos no estudo apresentaram RCEU na alta hospitalar. Influenciaram a taxa de variação do peso ao longo da internação hospitalar: o menor peso ao nascer, sexo masculino, menor Apgar de 5o minuto, o maior escore CRIB; persistência do canal arterial, doença metabólica óssea, hemorragia intracraniana, displasia broncopulmonar e sepse. O maior tempo em oxigenioterapia, as transfusões sanguíneas, o uso de diurético, o maior tempo para atingir dieta plena e de uso de nutrição parenteral também foram preditores do crescimento. A desnutrição de recém-nascidos prematuros MBPN nas Unidades Neonatais é um problema frequente e influenciado tanto pelo cuidado neonatal quanto pelas características individuais de cada criança.

Influência do refluxo duodenogástrico nas alterações histológicas da mucosa gástrica em ratos infectados por Helicobacter pylori: modelo experimental

O Helicobacter pylori, é tido como o principal fator de risco para o carcinoma gástrico. Diferentes estudos experimentais em animais procuram relacionar essa carcinogênese a outros fatores carcinógenos sem sucesso. Neste estudo, procurou-se avaliar-se em ratos, se há correlação entre o refluxo duodenogástrico, o Helicobacter pylori e o desenvolvimento do câncer gástrico ou de seus precursores. Para tal, realizou-se nos três grupos de ratos (n de dez por grupo) as técnicas de: piloroplastia precedida de infecção, gastrectomia subtotal precedida de infecção e um grupo no qual foi praticada apenas a infecção. Apois seis meses, analisou-se as alterações da mucosa, comparando-se os três grupos. As alterações da mucosa pesquisadas foram as seguintes: gastrites, metaplasias, displasias e neoplasias epiteliais. Ao término do estudo, foi encontrado, no grupo submetido a piloroplastia precedida de infecção um alto percentual de alterações epiteliais. Conclui-se que, no rato, a operação de piloroplastia, levou ao maior desenvolvimento da população do Helicobacter pylori, que se relaciona com as lesões pré- malignas e o adenocarcinoma gástrico.

Análise do efeito do etanol sobre a expressão de proteínas de diferenciação do epitélio escamoso no esôfago de camundongos BALB/c

Câncer de esôfago (CE) é um dos tipos de câncer mais frequentes e agressivos, estando entre os dez tipos de câncer mais incidentes e letais no mundo. Entre as regiões mais incidentes do CE estão os países em desenvolvimento, como o Brasil. Apesar de recentes avanços em terapias anticâncer, menos de 10% dos pacientes acometidos por esta doença possuem uma sobrevida maior que cinco anos após seu diagnóstico e este fato é consequência do diagnóstico tardio, uma vez que os sintomas só aparecem em estádios bem avançados. Devido a este panorama há uma grande busca por métodos e, principalmente, biomarcadores de diagnóstico que possam detectar a doença em estádios iniciais e assim aumentar a sobrevida dos pacientes. A discriminação entre tumor e mucosa normal é possível ser feita endoscopicamente, porém, para detecção precoce de tumores esofágico seria importante discriminar mucosa saudável de lesão precursora, como displasia. Uma diferença típica entre tecido normal e displasia é a perda de diferenciação celular, sugerindo que proteínas de diferenciação possam ser um potencial alvo para serem usadas como biomarcadores de detecção precoce em câncer. Citoqueratinas (CKs) e esofagina (SPRR3) são importantes proteínas envolvidas na diferenciação das células no epitélio escamoso. A proteína (SPRR3) vem sendo estudada como um possível biomarcador de detecção de tumores em estádios iniciais de desenvolvimento. Em CE tem sido descrito perda da expressão de SPRR3 quando comparada com a mucosa saudável. Além disso, já foi mostrado que a análise combinada da expressão das duas variantes de SPRR3 (SPRR3-v1 e SPRR3-v2) é capaz de discriminar a mucosa esofágica de indivíduos saudáveis da mucosa adjacente e do tumor com alta sensibilidade e especificidade. Porém, uma associação significativa foi encontrada entre uma menor expressão de SPRR3-v2 e o consumo de álcool. Este dado gerou a hipótese de que o álcool pode levar a carcinogênese por estimular a proliferação e/ou perda de diferenciação do epitélio escamoso e desta forma contribuir para o surgimento do tumor. Para testar esta hipótese, foi realizado um modelo experimental utilizando camundongos BABL/c que receberam diariamente etanol em diferentes concentrações por diferentes intervalos de tempo. Foram analisados critérios de toxicidade dos animais e critérios para avaliação histopátológica no tecido esofágico. Além disso, foi analisado o perfil de expressão de proteínas envolvidas em diferenciação e proliferação celular que pudessem sugerir alterações no epitélio esofágico induzidas pelo etanol, sendo estas SPRR3, CK5/8 e CK14 e Ki67. Inflamação foi a única alteração histológica encontrada, porém ocorreu de forma aleatória, não podendo, portanto, ser associada ao etanol. Alteração no padrão de expressão das proteínas analisadas foi encontrada em regiões inflamadas. Porém, a maioria das amostras não apresentou alterações histopatológicas, nem tampouco alteração de expressão das proteínas, sugerindo que em epitélio esofágico de camundongos BALB/c o etanol não é capaz de induzir isoladamente alteração na proliferação e perda de diferenciação celular.

Saberes e práticas das mães sobre o uso de broncodilatador em crianças com displasia broncopulmonar no domicílio: subsídios para a enfermagem pediátrica

Esta pesquisa teve como objeto de estudo os saberes e práticas das mães sobre o uso de broncodilatador em crianças com displasia broncopulmonar, e como objetivos: desvelar os saberes e práticas das mães sobre o uso de broncodilatador em seus filhos com displasia broncopulmonar no domicílio; conhecer os cuidados realizados pelas mães no uso do broncodilatador em seu filho com displasia broncopulmonar no domicílio e descrever as reações percebidas pelas mães em seus filhos após o uso da medicação. Trata-se de um estudo descritivo com abordagem qualitativa. O cenário foi um ambulatório de pneumologia localizado no Município do Rio de Janeiro e os sujeitos, 14 mães de crianças portadoras de displasia broncopulmonar, com idades entre 0 e 2 anos. A coleta dos dados foi realizada através da entrevista semiestruturada, no mês de julho de 2014. Utilizada a análise de conteúdo de Bardin. Como resultados, emergiram duas categorias: os saberes e medos das mães sobre o uso do broncodilatador eas práticas de cuidado da mãe na administração do broncodilatador na criança. A primeira categoria compreende quatro subcategorias: conhecimento das mães sobre a ação do medicamento; sinais de alerta percebidos pelas mães para o uso do medicamento na criança; os efeitos percebidos pelas mães após o uso do medicamento na criança e os medos relacionados ao uso do broncodilatador.A segunda categoria abrange três subcategorias: cuidados com o posicionamento da criança; cuidados com a higiene da criança e cuidados com o espaçador. A maioria das mães consegue identificar a partir dos seus saberes e de seu universo vocabular as principais ações dos broncodilatadores, no entanto podem-se evidenciar alguns relatos com informações inconsistentes, o que nos faz supor a ausência de orientações por parte dos profissionais junto a essa clientela. O esforço respiratório configura-se como sinal de alerta para que as mães utilizem a medicação para tentar evitar a crise respiratória. Sobre as alterações da criança após o uso do broncodilatador, a respiração melhorada surge como prevalente seguida da agitação. Sobre os medos que envolvem o uso do medicamento, as mães destacam aqueles relacionados ao efeito colateral, chegando a realizar subdose da droga a fim de evitá-lo. Com relação às práticas de cuidado das crianças, as mães não possuem consenso acerca da melhor posição para administrar a medicação, baseando suas escolhas em um melhor posicionamento para a criança, para ela mesma e para a eficácia da dose. Elas mencionaram realizar a higiene oral da criança após o uso do medicamento, porém não sabem o motivo correto da ação, denotando novamente que o processo educativo foi baseado em uma metodologia depositária, onde o indivíduo apenas memoriza o que foi aprendido. Conclui-se que o enfermeiro enquanto profissional educador em saúde precisa lançar mão de estratégias baseadas na problematização, dando voz a essas mães, conhecendo sua realidade e visão de mundo para que dessa maneira ela possa atrelar os seus saberes adquiridos com os saberes científicos, possibilitando uma adequada abordagem terapêutica junto aos seus filhos.

过量Mg~(2+)对农作物种子萌发特性的影响(英文)

[Objective] The research aimed to reveal the effects of excessive Mg2+ on the germination characteristics of maize and soybean. [Method] Eleven concentration gradients of Mg2+ including 0,40,80,120,160,200,240,280,320,360 and 400 mmol/L were set up to study the effects of different treatments on such indices as the germination potential,germination rate,fresh weight,dry weight,root length,plant height and stem diameter of maize and soybean. [Result] With the increasing of Mg2+ concentration,the germination of maize delayed and the germination rate of soybean obviously decreased,reaching the significant difference at 0.05 level. When Mg2+ concentration increased,the fresh weight and dry weight of maize and soybean decreased,but maize and soybean showed some adaptability. The growth of radicles and seedlings in maize and soybean were obviously inhibited by Mg2+,and atrophy and dysplasia phenomena appeared. [Conclusion] Excessive Mg2+ stress has different effects on the germination potential and germination rate of different crops and has obvious poisoning effects on the root and stem growth of crops.

基底神经节的认知和记忆功能研究

The cognition and memory functions of the Basal Ganglia have been the focus of contemporary cognitive neuroscience researches. This study, from neuroanatomical and neurophysiological point of view, thoroughly surveyed the recent relevant research progress, carefully examined the evidences of the neurological basis for the Basal Ganglia possessing or participating cognition or memory functions. Moreover, it reviewed recent achievements on the cognitive functions of the basal ganglia based on researches on rodent animals, primate animals and human beings. Then it presented a series of experiments conducted, by neuropsychological and cognitive psychological methods, on neurological patients with focal lesions to the basal ganglia or combining with bilateral hippocampus or thalamus impaired to explore what the role of the basal ganglia play in human explicit and implicit memory. It was found that the lesions to the basal ganglia partially handicapped explicit verbal memory and completely impaired perceptual priming. It was also found that right cerebral cortex dysplasia but basal ganglia spared had no effects on priming tasks performances. The results suggested that the basal ganglia contain or accommodate higher cognitive functions and further suggested that priming be irrelevant to right cerebral cortex. It was posited that the basal ganglia, on the basis of interaction with prefrontal or temporal cortices, mediate movement function as well as cognition and memory functions.

Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease.

Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation.

Familial expansile osteolysis (FEO) is a rare disorder causing bone dysplasia. The clinical features of FEO include early-onset hearing loss, tooth destruction, and progressive lytic expansion within limb bones causing pain, fracture, and deformity. An 18-bp duplication in the first exon of the TNFRSF11A gene encoding RANK has been previously identified in four FEO pedigrees. Despite having the identical mutation, phenotypic variations among affected individuals of the same and different pedigrees were noted. Another 18-bp duplication, one base proximal to the duplication previously reported, was subsequently found in two unrelated FEO patients. Finally, mutations overlapping with the mutations found in the FEO pedigrees have been found in ESH and early-onset PDB pedigrees. An Iranian FEO pedigree that contains six affected individuals dispersed in three generations has previously been introduced; here, the clinical features of the proband are reported in greater detail, and the genetic defect of the pedigree is presented. Direct sequencing of the entire coding region and upstream and downstream noncoding regions of TNFRSF11A in her DNA revealed the same 18-bp duplication mutation as previously found in the four FEO pedigrees. Additionally, eight sequence variations as compared to the TNFRSF11A reference sequence were identified, and a haplotype linked to the mutation based on these variations was defined. Although the mutation in the Iranian and four of the previously described FEO pedigrees was the same, haplotypes based on the intragenic SNPs suggest that the mutations do not share a common descent.

Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by gastric and duodenal reflux.

Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal extra-hepatic tissues; however the protein is not detectable in these tissues but is expressed in a wide variety of tumors. CYP1B1 is responsible for the activation of a number of carcinogens present in tobacco smoke and food. A surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal reflux was used to determine CYP1B1 expression in premalignant esophageal tissue. Immunohistochemistry was performed using a modified amplified fluorescein tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa, submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux group. All regions of hyperplasia showed moderate or strong CYP1B1 immunoreactivity. Duodenal reflux induced a small number of premalignant changes: immunoreactivity was absent from the epithelium of squamous dysplasia (0/10), Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4). Moderate or strong immunoreactivity was observed in the majority (7/8) of squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in the lamina propria and submucosa in association with inflammation, regardless of the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in situ, or in association with inflammation may increase the production of carcinogenic metabolites, which may promote esophageal tumorigenesis.

Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome

The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification model was investigated to distinguish the distinct subclasses of pediatric and adult leukemia, as well as MDS. Overall, the accuracy of the diagnostic classification model for subtyping leukemia was approximately 93%, but this was not reflected for the MDS samples giving only approximately 50% accuracy. Discordant samples of MDS were classified either into acute myeloid leukemia (AML) or

Inhibition of histone deacetylase 2 increases apoptosis and p21(Cip1/WAF1) expression, independent of histone deacetylase 1

Histone deacetylases ( HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21(Cip1/WAF1) expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.