Clinical and therapeutic potential of protein kinase PKR in cancer and metabolism.

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease. We emphasise the importance of PKR as a molecular target for both conventional chemotherapeutics and emerging treatments based on novel drugs, and its potential as a biomarker and therapeutic target for several pathologies. Finally, we discuss the impact that the recent knowledge regarding PKR involvement in metabolism has in our understanding of the complex processes of cancer and metabolism pathologies, highlighting the translational research establishing the clinical and therapeutic potential of this pleiotropic kinase.

Working with the HL7 metamodel in a Model Driven Engineering context.

HL7 (Health Level 7) International is an organization that defines health information standards. Most HL7 domain information models have been designed according to a proprietary graphic language whose domain models are based on the HL7 metamodel. Many researchers have considered using HL7 in the MDE (Model-Driven Engineering) context. A limitation has been identified: all MDE tools support UML (Unified Modeling Language), which is a standard model language, but most do not support the HL7 proprietary model language. We want to support software engineers without HL7 experience, thus real-world problems would be modeled by them by defining system requirements in UML that are compliant with HL7 domain models transparently. The objective of the present research is to connect HL7 with software analysis using a generic model-based approach. This paper introduces a first approach to an HL7 MDE solution that considers the MIF (Model Interchange Format) metamodel proposed by HL7 by making use of a plug-in developed in the EA (Enterprise Architect) tool.

A Strategic Study about Quality Characteristics in e-Health Systems Based on a Systematic Literature Review.

e-Health Systems quality management is an expensive and hard process that entails performing several tasks such as analysis, evaluation, and quality control. Furthermore, the development of an e-Health System involves great responsibility since people's health and quality of life depend on the system and services offered. The focus of the following study is to identify the gap in Quality Characteristics for e-Health Systems, by detecting not only which are the most studied, but also which are the most used Quality Characteristics these Systems include. A strategic study is driven in this paper by a Systematic Literature Review so as to identify Quality Characteristics in e-Health. Such study makes information and communication technology organizations reflect and act strategically to manage quality in e-Health Systems efficiently and effectively. As a result, this paper proposes the bases of a Quality Model and focuses on a set of Quality Characteristics to enable e-Health Systems quality management. Thus, we can conclude that this paper contributes to implementing knowledge with regard to the mission and view of e-Health (Systems) quality management and helps understand how current researches evaluate quality in e-Health Systems.

Two decades of assistive technologies to empower people with disability: a systematic mapping study.

PURPOSE: Information and Communication Technologies have transformed our lives in different social areas, facilitating interpersonal relationships thanks to technological tools. In the specific case of people with disabilities, Assistive Technologies (ATs) break down barriers and increase opportunities to become active members of society with equal opportunities. MATERIALS AND METHODS: This paper presents a systematic mapping study that analyzes the current state-of-the-art of ATs proposed in the literature to support the empowering of people with disability. Specifically, this paper focuses on (1) describing a global vision of the scientific literature published in the last 20 years about ATs in the computer science field and (2) identifying research needs, gaps, and trends. RESULTS: For this purpose, an in-depth analysis of 389 primary studies is presented. The information obtained from the mapping process is also constrained. Concretely, 35 ATs versus 22 disabilities are compared, obtaining striking peaks for some disabilities described in the discussion. CONCLUSIONS: Finally, the findings show that several areas have been covered only lightly, revealing interesting future directions and challenges for junior researchers.

• ATs have the potential to break down barriers for people with disabilities, enabling them to participate more fully in society. This implies a need for rehabilitation programs to incorporate ATs into their strategies to enhance social inclusion.• Given the transformative role of ICT, rehabilitation programs should focus on helping people with disabilities develop the necessary technological skills to utilize ATs effectively.• This work highlights the diversity of ATs and disabilities, suggesting a need for personalized rehabilitation plans that match specific ATs to individual disabilities.• Rehabilitation professionals should be trained to assess and recommend appropriate ATs for each case. Rehabilitation programs should consider incorporating cutting-edge ATs and staying involved in research to contribute to future developments to cover gaps and challenges identified.

Comparison of the prevalence and distribution of human papillomavirus infection and cervical lesions between urban and native habitants of an Amazonian region of Peru.

We made a study of the prevalence of human papillomavirus (HPV) and cervix lesions in an Amazonian Bora native population (Bn) and compared it with the prevalence in an urban population in Iquitos (Iq). We also examined the distribution of HPV types among abnormal cervical smears in the Iq population. Swabs and cytologies were collected from 472 females. DNA consensus PCR, followed by direct sequencing, were used to determinate the HPV types in the swabs. Cytologies were classified based on the lesion grade. HPV prevalence was 43.9% in Iq and 35.4% in Bn. Cervix lesion prevalence was 20.0% in Iq and 0.3% in Bn. The frequency of high-risk HPV types among HPV+ females was 71.9% in Iq and 56.3% in Bn. The frequencies of low-risk and undetermined risk HPV types were 19.3/6.3% (Iq/ Bn) and 12.3/37.5% (Iq/Bn), respectively. In lesIq (women seeking cytological services with a previous cervix lesion diagnosis) the prevalence of HPV, was 72.9%. The incidence of carcinoma and high-grade squamous intraepithelial cervix lesions in lesIq were 31.2 and 18.8%, respectively. The Bn population had a lower incidence of high-risk HPV and cervix lesions. The high-risk strain HPV16 was significantly more frequent in Iq compared with Bn. lesIq high-risk HPVs were more frequent in high-grade squamous intraepithelial lesions and carcinoma. High-risk HPV16 prevalence was significantly higher than the prevalence of the other high-risk HPVs, especially in the high-grade squamous intraepithelial lesions and carcinoma.

From bench to bedside: Biosensing strategies to evaluate endocrine disrupting compounds based on epigenetic events and their potential use in medicine.

The relationship between endocrine system disorders and health risks due to chemical environmental compounds has become a growing concern in recent years. Involuntary exposure to endocrine disruptors (EDCs) is associated with the worldwide increase of diseases such as cancer, obesity, diabetes, and neurocortical disorders. EDCs are compounds that target the nuclear hormonereceptors (NHR) leading to epigenetic changes. Consequently, the use of biosensing strategies based on epigenetic events have a great potential to provide outstanding information about the exposition of EDCs and their evaluation in human health. This review addresses the novel trends in biosensing EDCs evaluation based on DNA methylation assays associated with different human diseases.

Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

The usefulness of antibodies to the BRCA1 protein in detecting the mutated BRCA1 gene. An immunohistochemical study.

AIM: To assess the value of immunohistochemistry in discriminating between BRCA1 associated and non-BRCA1 associated breast tumours. METHODS: Four commercially available anti-BRCA1 antibodies were used on 45 paraffin wax embedded tumoral samples from patients with (seven of 45) and without (38 of 45) BRCA1 germline mutations. In all patients, the BRCA1 gene had been studied previously by means of the protein truncation test (PTT), conformational sensitive gel electrophoresis (CSGE), and direct sequencing of genomic DNA. Immunohistochemistry was carried out using the standard avidin-biotin immunoperoxidase method. Antigen retrieval was carried out by means of microwave pretreatment or autoclaving. The antibody panel used comprised D-20 (1/500), I-20 (1/100), K-18 (1/100), and MS110 (Ab-1; 1/50). RESULTS: No immunohistochemical differences in BRCA1 protein expression were found between cases with and without BRCA1 germline mutations. All positive cases showed predominantly cytoplasmic staining, in both tumoral and non-tumoral cells, with the polyclonal antibodies D-20, I-20, and K-18. After heating pretreatment both nuclear and cytoplasmic staining were found in tumoral and non-tumoral cells with the I-20 antibody. Only the monoclonal antibody MS110 showed a predominantly nuclear staining after microwave oven treatment. CONCLUSIONS: Commercially available BRCA1 antibodies lack the specificity required to identify the BRCA1 protein and thus are not useful for establishing differences between familial and sporadic breast tumours, or between BRCA1 associated and non-BRCA1 associated breast tumours.

Relationship between low bone mineral density and highly active antiretroviral therapy including protease inhibitors in HIV-infected patients.

PURPOSE: The objectives of this study were to determine the prevalence of osteopenia and the factors associated with its presence in HIV-infected patients under highly active antiretroviral therapy (HAART) and to assess the changes of bone mineral density (BMD) in a population followed prospectively. METHOD: BMD was assessed by dual-energy X-ray absorptiometry (DEXA) scans at the lumbar spine and at the femoral neck in 78 HIV-infected patients who had previously received HAART as the first antiretroviral regimen and in 11 antiretroviral-naive HIV-infected patients. BMD measurements were repeated in 70 treated patients who had completed 1 year of follow-up. RESULTS: Thirty-seven (42%) patients showed osteopenia at any localization. The prevalence of osteopenia in PI-naive patients was 23% versus 49% in individuals who had received PI at any moment [p =.001; adjusted odds ratio (95% CI) = 0.11 (0.02-0.48)]. The frequency of osteopenia was significantly higher among men than among women [50% vs. 17%; p =.016; adjusted OR (95% CI) = 12.1 (2.22-66.20)]. The level of plasma albumin was independently associated with osteopenia [adjusted OR (95% CI) per each g/dL of plasma albumin decrease 2.55 (1.18-10)]. In patients in whom a second DEXA was done, no significant changes in BMD were found. CONCLUSION: The prevalence of osteopenia in HIV-infected patients on HAART is high. Loss of BMD is associated with PI therapy, low plasma albumin level, and male sex. Osteopenia does not progress after 1 year of continued HAART.

Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus-coinfected patients.

Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent studies have reported that IR is associated with liver fibrosis progression in these patients. However, there is no information available on this issue in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. For these reasons, we investigate the relationship between IR and liver fibrosis in patients with HIV and HCV infections. This was a cross-sectional study where patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent a liver biopsy, with available frozen sera samples at the time of biopsy and a known or estimated date of infection were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. The relationship between histological findings and several variables, including HOMA-IR values, was examined. Seventy-nine patients fulfilled the inclusion criteria. Age at HCV infection >21 years was the only variable independently associated with advanced liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence interval (CI) 1.5-11.3]. The variables associated with a fibrosis progression rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16-27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01-39.36). There was no association between HOMA-IR values and the presence of advanced fibrosis or a faster fibrosis progression. Thus IR is not associated with liver damage or fibrosis progression in HIV/HCV-coinfected individuals.

Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes.

BACKGROUND: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. AIM: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. PATIENTS: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. METHODS: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. RESULTS: The models performed better when liver biopsies>or=15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27-34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. CONCLUSIONS: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.

[Prevalence of serum antibodies against Bartonella ssp. in a health population from the south area of the Seville province]. / Prevalencia de anticuerpos séricos frente a Bartonella spp. en una población sana del área sur de la provincia de Sevilla.

OBJECTIVE: To know the prevalence of serum antibodies against Bartonella spp. in a healthy population from south of Spain. PATIENTS AND METHODS: A clinical-epidemiological survey was conducted among 146 healthy individuals. An indirect immunofluorescence commercial technique was used in a sample of serum from each individual to detect the present of IgG type serum antibodies against Bartonella spp., considering a result equal to or greater than 1:128 as positive. RESULTS: Thirty six (24.7%) of all the subjects studied were asymptomatic carriers of antibodies against Bartonella spp. No crossed reactions against Chlamydia trachomatis, C. pneumoniae or Coxiella burnetti were observed. No significant association was found between the presence of seropositivity for Bartonella spp. and other factors. CONCLUSION: There is an elevated frequency of asymptomatic carriers of antibodies against Bartonella spp. among the healthy population of our area. This suggests that most of the infections by Bartonella are subclinical.

[Texas revised inventory of grief: adaptation to Spanish, reliability and validity]. / Inventario Texas Revisado de Duelo (ITRD): adaptación al castellano, fiabilidad y validez.

OBJECTIVES: To adapt into Spanish the Texas Revised Inventory of Grief (TRIG) of Faschinbaguer et al (1977, 1981) and to examine its reliability and validity. DESIGN: Two stages: a) cross-culture adaptation of a questionnaire, and b) cross-sectional study of reliability and validity. SETTING: Primary care teams in Vizcaya, north of Spain. PARTICIPANTS: 118 people who had been widowed between 3 months and 3 years before the study. MAIN MEASUREMENTS AND RESULTS: Cross-culture adaptation: the TRIG was translated from American English, then back-translated and finally compared with the version in American Spanish by Grabowski & Frantz (1993). Reliability: the Cronbach's alpha coefficients (internal consistency) of the 2 TRIG scales were 0.75 and 0.86. Factorial validity: all items except one threw saturation >0.40 on the 2 factors extracted from the varimax rotation. Validity by hypothesis: the TRIG scales showed differences (P<.05) between the grieving in terms of the expected or unexpected character of death, the place where death occurred and time elapsed since the death. The scores on the adapted TRIG were similar to scores on the American Spanish TRIG for Latins and higher than those on the original TRIG and the American Spanish TRIG for Anglo-saxons. Convergent validity: the 2 TRIG scales correlated positively (P<.05) with all the clinical scales on the Inventory of Grief Experiences of Sanders et al (1985) and García García et al (2001). CONCLUSIONS: In the evaluation of grief due to the death of the spouse, the TRIG adapted to Spanish is as reliable and valid as the original version.

[Inventory of experiences in grief (IEG): adaptation to Spanish, reliability and validity]. / Inventario de experiencias en duelo (IED): adaptación al castellano, fiabilidad y validez.

OBJECTIVE: To adapt to Castilian the Inventory of Experiences of Grief (IEG) of Catherine Sanders et al. (1977) and study its reliability and validity. DESIGN: In two stages: cross-cultural adaptation of a questionnaire and cross-sectional study with control group. SETTING: Primary care teams in Vizcaya. PARTICIPANTS: 147 people bereaved in the period between 3 months and 3 years before the study, and 36 who had lost no direct family member in the previous 5 years. MEASUREMENTS AND MAIN RESULTS: The IEG in American English was translated, back-translated and finally reviewed by Sanders and her colleagues, whose valuation was that the Castilian version was the same as the original. Reliability: the internal consistency of each of the scales of grief on the IEG (Cronbach's alpha) ran from 0.43 to 0.85. Factor validity: the first IEG factor adapted was similar to the original one (despair, somatization, anger, blame, depersonalisation and social isolation). Discriminating validity: all the grief scales on the IEG, except anxiety in face of death, discriminated (p < 0.05) between grieving and not grieving. Validity by hypothesis: the IEG scales showed differences (p < 0.05) between the bereaved according to sex, age, place of death of the spouse and time elapsed since death. Convergent validity: all the IEG grief scales correlated positively (p < 0.05) with the scales in the Texas Revised Inventory of Grief. CONCLUSIONS: The IEG adapted to Castilian is equivalent to the original and has similar reliability and validity.

[Grief for loss of a spouse: a study with discussion groups in primary care]. / El duelo por la pérdida del cónyuge: un estudio mediante grupos de discusión en atención primaria.

OBJECTIVE: To understand the grieving process after the loss of a spouse and to find the opinion of the person grieving about the best intervention under the circumstances. DESIGN: Qualitative, with discussion groups. SETTING: Primary care. PATIENTS AND OTHER PARTICIPANTS: Widowers/widows between 30 and 70, who suffered their loss between 3 months and 2 years before the study. MEASUREMENTS AND MAIN RESULTS. The data were obtained from recordings and transcriptions, and the main ideas analysed. Two groups were defined: 11 widows between 49 and 68 years old and 6 widowers between 36 and 70. The majority of deaths had followed a previous terminal illness. Four phases of grief were found: 1) anticipated grief, 2) early grief, 3) intermediate grief and 4) delayed grief. There were differences between widows and widowers. An intervention could involve: pre-arranged appointments, home visits, and groups and, in general, spaces to be able to "talk". CONCLUSIONS: The results, in so far as they refer to the grieving process and similarities and differences of type, coincide with other authors. The participants highlighted the importance of psychological support from health workers during the last moments of the illness and the importance of this in how grieving developed. Similarly, they evaluated their own support to the dying spouse as an additional factor which helped them.