Marine protected areas promote stability of reef fish communities under climate warming.

Protection from direct human impacts can safeguard marine life, yet ocean warming crosses marine protected area boundaries. Here, we test whether protection offers resilience to marine heatwaves from local to network scales. We examine 71,269 timeseries of population abundances for 2269 reef fish species surveyed in 357 protected versus 747 open sites worldwide. We quantify the stability of reef fish abundance from populations to metacommunities, considering responses of species and functional diversity including thermal affinity of different trophic groups. Overall, protection mitigates adverse effects of marine heatwaves on fish abundance, community stability, asynchronous fluctuations and functional richness. We find that local stability is positively related to distance from centers of high human density only in protected areas. We provide evidence that networks of protected areas have persistent reef fish communities in warming oceans by maintaining large populations and promoting stability at different levels of biological organization.

The MPA Guide: A framework to achieve global goals for the ocean.

Marine Protected Areas (MPAs) are conservation tools intended to protect biodiversity, promote healthy and resilient marine ecosystems, and provide societal benefits. Despite codification of MPAs in international agreements, MPA effectiveness is currently undermined by confusion about the many MPA types and consequent wildly differing outcomes. We present a clarifying science-driven framework­The MPA Guide­to aid design and evaluation. The guide categorizes MPAs by stage of establishment and level of protection, specifies the resulting direct and indirect outcomes for biodiversity and human well-being, and describes the key conditions necessary for positive outcomes. Use of this MPA Guide by scientists, managers, policy-makers, and communities can improve effective design, implementation, assessment, and tracking of existing and future MPAs to achieve conservation goals by using scientifically grounded practices.

Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease.

BACKGROUND: The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. OBJECTIVE: This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. METHODS: Patients with PBC as main diagnosis were included from a national multicentric patient registry-Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. RESULTS: A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti-mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow-up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02-1.54; p = 0.033) and 35% (95%CI:1.06-1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01-1.10; p = 0.013) for those with elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP). CONCLUSION: A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization.

Weak biodiversity connectivity in the European network of no-take marine protected areas.

The need for international cooperation in marine resource management and conservation has been reflected in the increasing number of agreements aiming for effective and well-connected networks of Marine Protected Areas (MPAs). However, the extent to which individual MPAs are connected remains mostly unknown. Here, we use a biophysical model tuned with empirical data on species dispersal ecology to predict connectivity of a vast spectrum of biodiversity in the European network of marine reserves (i.e., no-take MPAs). Our results highlight the correlation between empirical propagule duration data and connectivity potential and show weak network connectivity and strong isolation for major ecological groups, resulting from the lack of direct connectivity corridors between reserves over vast regions. The particularly high isolation predicted for ecosystem structuring species (e.g., corals, sponges, macroalgae and seagrass) might potentially undermine biodiversity conservation efforts if local retention is insufficient and unmanaged populations are at risk. Isolation might also be problematic for populations' persistence in the light of climate change and expected species range shifts. Our findings provide novel insights for management directives, highlighting the location of regions requiring additional marine reserves to function as stepping-stone connectivity corridors.

Expression and Characterization of Human Vascular Endothelial Growth Factor Produced in SiHa Cells Transduced with Adenoviral Vector.

The vascular endothelial growth factor (VEGF) is an essential factor to pathologic angiogenesis. Disruption of VEGF/VEGF receptor interaction in cancer patients inhibits the development of new and pre-existing tumor blood vessels. Consequently, VEGF becomes an important therapeutic target for handling solid tumors. In this work, human VEGF was produced in the culture supernatant of SiHa cells transduced with a replication-defective adenoviral vector (pAdhVEGF121) encoding this molecule. The 35 kDa VEGF121 homodimer was obtained from clarified culture media as a glycosylated protein. VEGF121 expression levels were strictly dependent on the adenoviral viral load used. VEGF121 was produced with purity over 98% after a single step chromatography by immobilized metal affinity chromatography. Additionally, VEGF121 binds Bevacizumab antibody with a KD of 7 nM. Biological characterization by mitogenic assay in HUVEC and ECV-304 cells showed that VEGF121 stimulates cell proliferation in a dose-dependent manner in both cells. Finally, the neovascularization activity of VEGF121 was demonstrated by vascular permeability assays in matrigel plug-bearing mice, showing significantly increased vasculature leakage after treatment with VEGF121. Consequently, transduction of SiHa cells with adenovirus is a suitable alternative for manufacture heterologous proteins of therapeutic interest.

LOX-1 activation by oxLDL triggers an epithelial mesenchymal transition and promotes tumorigenic potential in prostate cancer cells.

Obesity is related to an increased risk of developing prostate cancer with high malignancy stages or metastasis. Recent results demonstrated that LOX-1, a receptor associated with obesity and atherosclerosis, is overexpressed in advanced and metastatic prostate cancer. Furthermore, high levels of oxLDL, the main ligand for LOX-1, have been found in patients with advanced prostate cancer. However, the role of LOX-1 in prostate cancer has not been unraveled completely yet. Here, we show that LOX-1 is overexpressed in prostate cancer cells and its activation by oxLDL promotes an epithelial to mesenchymal transition, through of lowered expression of epithelial markers (E-cadherin and plakoglobin) and an increased expression of mesenchymal markers (vimentin, N-cadherin, snail, slug, MMP-2 and MMP-9). Consequently, LOX-1 activation by oxLDL promotes actin cytoskeleton restructuration and MMP-2 and MMP-9 activity inducing prostate cancer cell invasion and migration. Additionally, LOX-1 increased the tumorigenic potential of prostate cancer cells and its expression was necessary for tumor growth in nude mice. In conclusion, our results suggest that oxLDL/LOX-1 could be ones of mechanisms that explain why obese patients with prostate cancer have an accelerated tumor progression and a greater probability of developing metastasis.

Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress.

Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR), it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL) was purified from skimmed goat milk. Recombinant human erythropoietin (Epo) was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP); cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15min of oxygen and glucose deprivation (OGD) and the neuroprotective drugs EpoL or Epo were incubated for 2h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases.

Cuidar da criança em processo paliativo e da sua família: estratégias de enfermagem que visam a gestão emocional nos irmãos / Caring for children in palliative care and their families: nursing strategies aimed at emotional management in siblings

A criança com necessidades paliativas torna-se, inevitavelmente, o foco da atenção e preocupação dos pais. As hospitalizações e consultas médicas frequentes quebram a rotina e as relações familiares, colocando os irmãos em segundo plano, ficando, estes, frequentemente em casa de familiares ou amigos, com um frágil suporte. Concomitantemente, os feriados, férias e outros eventos especiais não são aproveitados da mesma forma e os pais podem não ser capazes de comparecer às atividades escolares ou outras atividades dos irmãos, podendo, igualmente, as relações não serem de qualidade pois, os pais, podem não estar física e emocionalmente disponíveis para eles. Também, os recursos financeiros são direcionados para a criança doente. Estes fatores, isolada ou cumulativamente, podem afetar os irmãos, fragilizando-os emocionalmente, podendo, mesmo, afetar o seu desenvolvimento emocional e/ou saúde mental. Neste sentido, a temática deste relatório incide no cuidar da criança em processo paliativo e da sua família, com enfoque no suporte emocional dos irmãos. Os enfermeiros, na prestação de cuidados, devem atender às vivências dos irmãos da criança, para minimizar as necessidades e repercussões da doença da criança nos irmãos. Assim, como objeto de estudo pretende-se desenvolver estratégias de enfermagem que visam a gestão emocional dos irmãos. A sua finalidade é aprofundar saberes práticos, impulsionando uma mudança nas práticas de enfermagem, com reflexo na melhoria contínua da qualidade dos cuidados pediátricos. A metodologia adotada consiste na reflexão sobre a prática e na aprendizagem experiencial desenvolvida em diferentes estágios de cuidados de saúde pediátricos. Das atividades de estágio destacam-se: a identificação das necessidades emocionais dos irmãos, identificação das estratégias de comunicação utilizadas na prestação de cuidados, entrevistas semiestruturadas para explorar a dimensão emocional dos cuidados e o luto fraterno, jornais de aprendizagem, diários de campo e ações de formação. As estratégias de enfermagem implementadas no âmbito do trabalho emocional em enfermagem pediátrica contribuem para uma melhor adaptação psicossocial dos irmãos da criança em processo paliativo, bem como para a redução das necessidades sentidas pelos mesmos.

The child with palliative needs inevitably becomes the focus of parental attention and concern. Hospitalizations and frequent medical appointments break routine and family relationships, putting siblings in the background, often staying with relatives or friends with fragile support. At the same time, holidays, vacation and other special events are not used in the same way and parents may not be able to attend school activities or other sibling activities often, likewise, relationships may not be of quality because parents may not be physically and emotionally available to them. Also, the financial resources are directed to the sick child. These factors, isolated or cumulatively, can affect the siblings, debilitating them emotionally, and can even affect their emotional development and/or mental health. In this sense, the theme of this report focuses on caring for the child in the palliative process and his family, focusing on the emotional support of the siblings. Nurses, in the provision of care, must attend to the experiences of the siblings of the child, to minimize the needs and repercussions of the child's illness in the siblings. Thus, the object of study is intended to develop nursing strategies that aim at emotional management in siblings. Its purpose is to deepen practical knowledge, fostering a change in nursing practices, with a reflection on the continuous improvement of the quality of pediatric care. The methodology adopted is the reflection on the practice and experiential learning developed in different internships of pediatric health care. Internships activities include the identification of the emotional needs of siblings, identification of communication strategies used in caregiving, semi-structured interviews to explore the emotional dimension of care and fraternal mourning, learning journals, field journals and training actions. The nursing strategies implemented in the context of emotional work in pediatric nursing contribute to a better psychosocial adaptation of the siblings of the child in a palliative process, as well as to the reduction of the needs felt by them.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases.

This article describes cases of anti-tumor necrosis factor (TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

AQP4 autoantibody assay performance in clinical laboratory service.

OBJECTIVE: To compare performance of contemporary aquaporin-4-immunoglobulin (Ig) G assays in clinical service. METHODS: Sera from neurologic patients (4 groups) and controls were tested initially by service ELISA (recombinant human aquaporin-4, M1 isoform) and then by cell-based fluorescence assays: fixed (CBA, M1-aquaporin-4, observer-scored) and live (fluorescence-activated cell sorting [FACS], M1 and M23 aquaporin-4 isoforms). Group 1: all Mayo Clinic patients tested from January to May 2012; group 2: consecutive aquaporin-4-IgG-positive patients from September 2011 (Mayo and non-Mayo); group 3: suspected ELISA false-negatives from 2011 to 2013 (physician-reported, high likelihood of neuromyelitis optica spectrum disorders [NMOSDs] clinically); group 4: suspected ELISA false-positives (physician-reported, not NMOSD clinically). RESULTS: Group 1 (n = 388): M1-FACS assay performed optimally (areas under the curves: M1 = 0.64; M23 = 0.57 [p = 0.02]). Group 2 (n = 30): NMOSD clinical diagnosis was confirmed by: M23-FACS, 24; M1-FACS, 23; M1-CBA, 20; and M1-ELISA, 18. Six results were suspected false-positive: M23-FACS, 2; M1-ELISA, 2; and M23-FACS, M1-FACS, and M1-CBA, 2. Group 3 (n = 31, suspected M1-ELISA false-negatives): results were positive for 5 sera: M1-FACS, 5; M23-FACS, 3; and M1-CBA, 2. Group 4 (n = 41, suspected M1-ELISA false-positives): all negative except 1 (positive only by M1-CBA). M1/M23-cotransfected cells expressing smaller membrane arrays of aquaporin-4 yielded fewer false- positive FACS results than M23-transfected cells. CONCLUSION: Aquaporin-4-transfected CBAs, particularly M1-FACS, perform optimally in aiding NMOSD serologic diagnosis. High-order arrays of M23-aquaporin-4 may yield false-positive results by binding IgG nonspecifically.

Management of autoimmune hepatitis: Focus on pharmacologic treatments beyond corticosteroids.

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use but it can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

Fishers' behaviour in response to the implementation of a Marine Protected Area.

Marine Protected Areas (MPAs) have been widely proposed as a fisheries management tool in addition to their conservation purposes. Despite this, few studies have satisfactorily assessed the dynamics of fishers' adaptations to the loss of fishing grounds. Here we used data from before, during and after the implementation of the management plan of a temperate Atlantic multiple-use MPA to examine the factors affecting the spatial and temporal distribution of different gears used by the artisanal fishing fleet. The position of vessels and gear types were obtained by visual surveys and related to spatial features of the marine park. A hotspot analysis was conducted to identify heavily utilized patches for each fishing gear and time period. The contribution of individual vessels to each significant cluster was assessed to better understand fishers' choices. Different fisheries responded differently to the implementation of protection measures, with preferred habitats of target species driving much of the fishers' choices. Within each fishery, individual fishers showed distinct strategies with some operating in a broader area whereas others kept preferred territories. Our findings are based on reliable methods that can easily be applied in coastal multipurpose MPAs to monitor and assess fisheries and fishers responses to different management rules and protection levels. This paper is the first in-depth empirical study where fishers' choices from artisanal fisheries were analysed before, during and after the implementation of a MPA, thereby allowing a clearer understanding of the dynamics of local fisheries and providing significant lessons for marine conservation and management of coastal systems.

Inhibition of ovine in vitro fertilization by anti-Prt antibody: hypothetical model for Prt/ZP interaction.

BACKGROUND: The impact of prion proteins in the rules that dictate biological reproduction is still poorly understood. Likewise, the role of prnt gene, encoding the prion-like protein testis specific (Prt), in ram reproductive physiology remains largely unknown. In this study, we assessed the effect of Prt in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization medium incubated with spermatozoa and oocytes. Moreover, a computational model was constructed to infer how the results obtained could be related to a hypothetical role for Prt in sperm-zona pellucida (ZP) binding. METHODS: Mature ovine oocytes were transferred to fertilization medium alone (control) or supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated with ovine spermatozoa and after 18 h, presumptive zygotes (n=142) were fixed to evaluate fertilization rates or transferred (n=374) for embryo culture until D6-7. Predicted ovine Prt tertiary structure was compared with data obtained by circular dichroism spectroscopy (CD) and a protein-protein computational docking model was estimated for a hypothetical Prt/ZP interaction. RESULTS: The fertilizing rate was lower (P=0.006) in APPA group (46.0+/-6.79%) when compared to control (78.5+/-7.47%) and CSerum (64.5+/-6.65%) groups. In addition, the cleavage rate was higher (P<0.0001) in control (44.1+/-4.15%) than in APPA group (19.7+/-4.22%). Prt CD spectroscopy showed a 22% alpha-helical structure in 30% (m/v) aqueous trifluoroethanol (TFE) and 17% alpha in 0.6% (m/v) TFE. The predominant alpha-helical secondary structure detected correlates with the predicted three dimensional structure for ovine Prt, which was subsequently used to test Prt/ZP docking. Computational analyses predicted a favorable Prt-binding activity towards ZP domains. CONCLUSIONS: Our data indicates that the presence of APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover, the CD analysis data reinforces the predicted ovine Prt trend towards an alpha-helical structure. Predicted protein-protein docking suggests a possible interaction between Prt and ZP, thus supporting an important role for Prt in ovine fertilization.

Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. In the present work, we aimed at investigating HCV genotype, variability and genetic history of HCV isolates in Cuba from a sample of chronically infected patients. MATERIAL AND METHODS: A prospective study, involving 73 Cuban anti-HCV positive patients, was carried out. RT-PCR and phylogenetic analysis was employed to determine HCV genotypes. Divergence dates and demographic parameters in a Bayesian coalescent framework were estimated, as implemented in BEAST v1.4.8. RESULTS: HCV RNA was undetectable in 15 patients that received antiviral therapy. All HCV RNA positive patients, 58, were infected with genotype 1, three of them with subtype 1a and 55 with subtype 1b. The analysis of the DNA sequence coding for a core fragment, spanning nt positions 435-816 (relative to strain H77), revealed high percent (96.7% +/- 0.8%) nucleotide identity within Cuban HCV subtype 1b sequences. However, 56.7% and 20% of 30 analyzed individuals had changes in the core region in a six-month interval, at the nucleotide and amino acid level, respectively. Mutations involving aa changes were mainly found in the region encompassed between aa 70 and 106 of the core protein, with only one isolate showing a point mutation at position 43. Interestingly, some of the observed changes seem to be reversions and might in fact contribute to reducing the variability of this region. The estimated date for the most recent common ancestor of HCV genotype 1b Cuban isolates is 1969 (CI, 1953 to 1977). DISCUSSION: Analysis of HCV core encoding sequences from chronic patients reveals mutability of genotype 1b isolates in Cuba, which seem to be predominant and rapidly multiplied during the eighty decade of last century, and might limit the benefits obtained from current antiviral therapy.

Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial.

SUMMARY: Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals.

Existe vida após o casamento? / Is there life after marriage?

O texto aborda aspectos de certos vínculos, nos quais a união, caracterizada por desgaste progressivo, deságua num simbólico duplo suicídio. Um filme de Takeshi Kitano é usado como ilustração dessa análise, num vôo sobre o teatro de marionetes e pela dramaturgia renascentista japoneses. Temos os consultórios como palcos dessas encenações e o desafio de colaborar para, quem sabe, evitarmos desenlaces tão trágicos (AU)

This essay addresses aspects of certain bonds in which the union is characterized by a progressive wearing out, leading to a symbolic double suicide. A film directed by Takeshi Kitano is used to illustrate the analysis, in an overview of marionette theatre and Japanese Renaissance drama. We have our consulting rooms as a stage for these performances and the challenge to possibly avoid such tragic consequences (AU)

The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C.

BACKGROUND/AIMS: Peginterferon alfa-2a plus ribavirin improves sustained virological responses compared with interferon alfa-2b and ribavirin, or peginterferon alfa-2a alone in chronic hepatitis C. We examined the impact of these treatments on health related quality of life (HRQOL). METHODS: Patients (n=1121) were randomized to peginterferon alfa-2a weekly plus ribavirin or placebo, or interferon alfa-2b thrice weekly plus ribavirin. HRQOL was assessed with the SF-36 Health Survey and Fatigue Severity Scale (FSS). RESULTS: Patients receiving peginterferon alfa-2a plus ribavirin reported better HRQOL than those receiving interferon alfa-2b plus ribavirin. These differences were statistically significant for three SF-36 domains and both FSS scores (p<=0.05). Patients receiving peginterferon alfa-2a plus placebo had the least impairment; adding ribavirin significantly decreased five domains of the SF-36 and both FSS scores. Sustained virological response was associated with improvement at follow-up on all SF-36 and FSS scores. CONCLUSIONS: The effects of combination therapy on HRQOL and fatigue are less with peginterferon alfa-2a plus ribavirin than interferon alfa-2b plus ribavirin. Each medication in combination therapy with interferon and ribavirin, affects patients' quality of life differently. Understanding the relationship of specific therapeutic options to HRQOL may help physicians minimize the impact of therapy on HRQOL.

Organic personality disorder after traumatic brain injury: cognitive, anatomic and psychosocial factors. A 6 month follow-up.

OBJECTIVE: The purpose of the study is to describe psychosocial adjustment in patients who present Organic Personality Disorder (OPD) after TBI in relation to patients with TBI without OPD. METHOD: The group included patients who were admitted as inpatients in the Neurology Service. Exclusion criteria were: previous personality disorders; previous alcohol and drugs addiction, history of head injury and other neurological diseases. For this purpose, a semi-structured interview based on the ICD-10 was applied to the patient or significant other during the 1st or 2nd week after the accident. Selected patients were evaluated with psychological and psychosocial tests and questionnaires 6 months after head injury, among them: WAIS, Benton Test, Rey Osterrieth Test, Wisconsin Cards, Psychosocial Scale and Neurobehavioural Rating Scale (NRS-27). RESULTS: No significant differences were observed in relation to demographic characteristics, type of head injury, GCS, or psychometric results. Significant differences were found in the answers to neurobehavioural and psychosocial questionnaires, showing more impairment in patients with OPD. CONCLUSIONS: The results show that, in this group, patients with OPD after TBI present more psychosocial adjustment and emotional problems than patients with TBI without OPD diagnosis. The difference found is independent of cognitive impairments.