Exploration of Patients' Spiritual/Religious Beliefs and Resuscitation Decisions.

Artificial resuscitation has potential to reverse a premature death or to prolong the dying process. The resuscitation decision is one of life and death making it imperative that healthcare providers understand patients' beliefs. Making the decision to resuscitate has been associated with patients' spiritual/religious beliefs. Clinicians' assumptions based upon a patients' religion or spiritual beliefs may bias the resuscitation decision. The purpose of this study was to determine associations between hospitalized patients' spiritual/religious beliefs and their resuscitation decisions. A single-site, correlational study was conducted with a convenience sample of hospitalized patients in Honolulu, HI. Patients were enrolled November 2015 to January 2016. Spiritual/religious beliefs were assessed using two validated metrics. Two questions were used to determine the resuscitation decision (chest compressions and intubation). The sample of 84 patients represented no ethnic majority among Caucasian, Asian, and Native Hawaiian/Pacific Islander. Seventy-nine percent of the participants identified theistic spiritual beliefs. No associations were found between resuscitation decisions with either spiritual/religious beliefs or demographic characteristics of this study sample. Interestingly, 20% of the participants answered yes to only one of the resuscitation decision questions. Thus, providers' assumptions should not be made about an association between spiritual/religious beliefs and resuscitation decisions. It is imperative that patients are aware of the necessity for both medical interventions of chest compressions and intubation. Further research should address the complexity of the resuscitation decision, including patients understanding of medical interventions and anticipated prognosis, and other influencing factors.

[Work ability and quality of life of Brazilian industrial workers]. / Capacidade para o trabalho e qualidade de vida de trabalhadores industriais.

The scope of this study was to evaluate the quality of life and work ability of industrial workers by means of self-perception questionnaires. 100 industrial production line workers on the night shift participated in this study. Authorized Brazilian translations of the Work Ability Index (WAI) and the Abbreviated World Health Organization Quality of Life (WHOQOL-Bref) Assessment Instrument were applied. The results show an association between work ability and the whole set of domains of quality of life, presenting a closer association with the physical domain (r =0.61). Furthermore, young men obtained higher ability to work results, while women aged between 30 and 39 had the lowest quality of life indices (p =0.027), especially in the Social Relationships and Environment domains. This shows that preventive guidelines for the improvement of aspects linked to the Physical domain are necessary both in the workplace and outside the workplace, since this interaction exacerbates the effects on the physical aspect in both spheres.

Capacidade para o trabalho e qualidade de vida de trabalhadores industriais / Work ability and quality of life of brazilian industrial workers

O objetivo do presente estudo foi avaliar, comparativamente, a qualidade de vida e a capacidade de trabalho de trabalhadores industriais, por meio dos índices de capacidade para o trabalho e de qualidade de vida. Participaram do estudo 100 trabalhadores de um setor noturno de linha de produção. Foram aplicadas traduções autorizadas do Índice de Capacidade para o Trabalho e o Instrumento Abreviado de Qualidade de Vida da Organização Mundial de Saúde. Os resultados evidenciam associação entre a capacidade para o trabalho e todo o conjunto dos domínios de qualidade de vida, apresentando melhor associação com o domínio Físico (r =0,61). Além disso, os homens jovens obtiveram valores maiores para Capacidade de Trabalho (p =0,016), enquanto que as mulheres com idade entre 30-39 anos apresentaram os piores índices de qualidade de vida (p =0,027), especialmente para os domínios Relações Sociais e Ambiente. Reforça-se, assim, a necessidade de diretrizes preventivas específicas para o aprimoramento dos aspectos ligados ao domínio Físico tanto no ambiente de trabalho como fora dele, uma vez que essa interação potencializa os efeitos no aspecto físico em ambas as esferas.

The scope of this study was to evaluate the quality of life and work ability of industrial workers by means of self-perception questionnaires. 100 industrial production line workers on the night shift participated in this study. Authorized Brazilian translations of the Work Ability Index (WAI) and the Abbreviated World Health Organization Quality of Life (WHOQOL-Bref) Assessment Instrument were applied. The results show an association between work ability and the whole set of domains of quality of life, presenting a closer association with the physical domain (r =0.61). Furthermore, young men obtained higher ability to work results, while women aged between 30 and 39 had the lowest quality of life indices (p =0.027), especially in the Social Relationships and Environment domains. This shows that preventive guidelines for the improvement of aspects linked to the Physical domain are necessary both in the workplace and outside the workplace, since this interaction exacerbates the effects on the physical aspect in both spheres.

Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection.

BACKGROUND AND AIMS: CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. METHODS: A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. RESULTS: A strong 'HLA footprint' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03-positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. CONCLUSIONS: It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies.

Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak.

UNLABELLED: The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. CONCLUSION: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.

Network dynamics in scientific knowledge acquisition: an analysis in three public universities in the state of Bahia

O propósito deste artigo é lançar luz sobre a dinâmica das redes de conhecimento, nos países em desenvolvimento, por meio da análise da produção científica da maior universidade do Nordeste do Brasil (UFBA) e sua influência sobre algumas instituições regionais de pesquisa no estado da Bahia. Através de um teste de metodologia, as produções científicas, especificamente no campo da química, da Universidade Federal da Bahia (UFBA), da Universidade do Estado da Bahia (Uneb) e da Universidade Estadual de Santa Cruz (Uesc) foram minuciosamente analisadas e cruzadas. Por meio da análise de redes sociais investigou-se a existência de pequenos fenômenos do mundo e a importância destes fenômenos na realização da pesquisa nas três universidades. Os resultados obtidos com a pesquisa elucidaram dados de grande interesse sobre a produção científica nessas universidades e comprovaram a importante participação da rede UFBA e das outras duas instituições públicas de pesquisa, bem como a importância dos pesquisadores na consolidação de redes. Este artigo também sugere que a metodologia pode ser adequada à medida que a produção científica seja utilizada como um substituto para o conhecimento científico.

Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen-restricted immune pressure.

UNLABELLED: Many hepatitis C virus (HCV) infections worldwide are with the genotype 1 and 3 strains of the virus. Cellular immune responses are known to be important in the containment of HCV genotype 1 infection, and many genotype 1 T cell targets (epitopes) that are presented by host human leukocyte antigens (HLAs) have been identified. In contrast, there is almost no information known about the equivalent responses to genotype 3. Immune escape mechanisms used by HCV include the evolution of viral polymorphisms (adaptations) that abrogate this host-viral interaction. Evidence of HCV adaptation to HLA-restricted immune pressure on HCV can be observed at the population level as viral polymorphisms associated with specific HLA types. To evaluate the escape patterns of HCV genotypes 1 and 3, we assessed the associations between viral polymorphisms and specific HLA types from 187 individuals with genotype 1a and 136 individuals with genotype 3a infection. We identified 51 HLA-associated viral polymorphisms (32 for genotype 1a and 19 for genotype 3a). Of these putative viral adaptation sites, six fell within previously published epitopes. Only two HLA-associated viral polymorphisms were common to both genotypes. In the remaining sites with HLA-associated polymorphisms, there was either complete conservation or no significant HLA association with viral polymorphism in the alternative genotype. This study also highlights the diverse mechanisms by which viral evasion of immune responses may be achieved and the role of genotype variation in these processes. CONCLUSION: There is little overlap in HLA-associated polymorphisms in the nonstructural proteins of HCV for the two genotypes, implying differences in the cellular immune pressures acting on these viruses and different escape profiles. These findings have implications for future therapeutic strategies to combat HCV infection, including vaccine design.

Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy.

UNLABELLED: The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with human immunodeficiency virus (HIV). We identified preexisting STAT-C drug resistance mutations in sequences from this large cohort. The frequency of the variations varied according to individual STAT-C drug and HCV genotype/subtype. Of individuals infected with subtype 1a, 21.5% exhibited genetic variation at a known drug resistance site. Furthermore, we identified areas in HCV protease and polymerase that are under both potential HLA-driven pressure and therapy selection and identified six HLA-associated polymorphisms (P

Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection.

Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level.

Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B.

Members of the killer immunoglobulin (Ig)-like receptor (KIR) gene family are tightly clustered on human chromosome 19q13.4. Despite considerable variation in KIR gene content and allelic polymorphism, most KIR haplotypes belong to one of two broad groups termed A and B. The availability of contiguous genomic sequences for these haplotypes has allowed us to compare their genomic organization, nucleotide (nt) diversity and reconstruct their evolutionary history. The haplotypes have a framework of three conserved blocks containing (i) KIR3DL3, (ii) KIR3DP1, 2DL4, and (iii) KIR3DL2 that are interrupted by two variable segments that differ in the number and type of KIR genes. Low (0.05%) nucleotide diversity was detected across the centromeric and telomeric boundaries of the KIR gene cluster while higher SNP density (0.2%) occurred within the central region containing the KIR2DL4 gene. Phylogenetic and genomic analyses have permitted the reconstruction of a hypothetical ancestral haplotype that has revealed common groupings and differences between the KIR genes of the two haplotypes. The present phylogenetic and genomic comparison of the two sequenced KIR haplotypes provides a framework for a more thorough examination of KIR haplotype variations, diversity and evolution in human populations and between humans and non-human primates.

Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth Disease.

In a previous study, we have shown that N-myc downstream-regulated gene 1 (NDRG1), classified in databases as a tumor suppressor and heavy metal-response protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease. The private founder mutation R148X, causing HMSNL in patients of Romani ethnicity, has so far remained the only molecular defect linking NDRG1 to a specific disease phenotype. Here we report the first study aiming to assess the overall contribution of this gene to the pathogenesis of peripheral neuropathies, in cases where the most common causes of CMT disease have been excluded. Sequence analysis of NDRG1 in 104 CMT patients of diverse ethnicity identified one novel disease-causing mutation, IVS8-1G>A (g.2290787G>A), which affects the splice-acceptor site of IVS8 and results in the skipping of exon 9. The phenotype of the IVS8-1G>A homozygote was very closely related to that of HMSNL patients. In addition, we have detected homozygosity for the known R148X mutation in two affected individuals. Mutations in NDRG1 thus accounted for 2.88% of our overall group of patients, and for 4.68% of cases with demyelinating neuropathies. No other variants were identified in the coding sequence, whereas 12 single nucleotide polymorphisms were observed in the introns. Hum Mutat 22:129-135, 2003.

The poliovirus receptor related 2 (PRR2) and apolipoprotein E genes and coronary heart disease.

BACKGROUND: Recently, we localized the Human Poliovirus Receptor Related 2 Gene (PRR2) 17kb centromeric to the gene for apolipoprotein E (APOE). Common polymorphisms in the latter have been found, in some studies, to be related to coronary heart disease (CHD) but the PRR2 gene has not been studied in this context. Here, we examined relationships between a PRR2 Sau96I (A/G) polymorphism, the epsilon2, 3 and 4 alleles of APOE and CHD. DESIGN AND METHODS: Consecutive Caucasian patients (n = 640) < 50 years with angiographically documented coronary obstructive disease and/or with unequivocal myocardial infarction were compared with 624 control subjects, aged 30-50 years, randomly selected from the community and without a history of CHD. RESULTS: An excess of PRR2-A homozygotes was observed in cases (20% vs. 15%; OR 1.4, CI 1.04-1.86, P = 0.026) particularly in those with single vessel disease (OR 1.7, CI 1.2-2.4, P <0.01). The A allele was in linkage disequilibrium with the epsilon4 allele and the G allele with the epsilon2. Overrepresentation of the A allele and underrepresentation of the G allele in the CHD group did not reach significance (P = 0.054). While the epsilon2 allele was underrepresented in the CHD group (OR 0.64, CI 0.46-0.89, P = 0.009), the epsilon4 allele was not significantly overrepresented. CONCLUSION: The relationship between the PRR2 Sau96I (A/G) polymorphism and early onset coronary artery disease may be due to linkage disequilibrium with the APOE gene and underrepresentation, or a protective effect, of the epsilon2 allele. Alternatively, since A allele homozygosity is particularly overrepresented, the relationship could be more direct, perhaps through a viral association.

Questäo agrária e saúde no Brasil contemporâneo / Agrarian problem and health in contemporary Brazil

Tendo como objetivo avaliar as condiçöes de saúde do trabalhador rural, o presente texto introduz o tema pela explicitaçäo da complexidade da questäo agrária no Brasil e suas implicaçöes para a saúde do trabalhador. Sendo a saúde um processo social derivado de condiçöes de vida e trabalho - um processo, portanto, multidimensional-, a açäo do Estado visando a recuperar e/ou a manter a saúde será, necessariamente, intersetorial. O direito à saúde é conquistado como um direito do cidadäo, implicando avanços nas condiçöes imediatas de trabalho, de alimentaçäo, de moradia e de saneamento básico. No Brasil, as dificuldades de ampliaçäo da cidadania do trabalhador em um quadro político que oscila do autoritarismo ao populismo - ambos cimentados pela política de clientela - revelam-se com maior nitidez para o trabalhador rural