Substrate specificity of human kallikrein 2 (hK2) as determined by phage display technology.

Human glandular kallikrein 2 (hK2) is a trypsin-like serine protease expressed predominantly in the prostate epithelium. Recently, hK2 has proven to be a useful marker that can be used in combination with prostate specific antigen for screening and diagnosis of prostate cancer. The cleavage by hK2 of certain substrates in the proteolytic cascade suggest that the kallikrein may be involved in prostate cancer development; however, there has been very little other progress toward its biochemical characterization or elucidation of its true physiological role. In the present work, we adapt phage substrate technology to study the substrate specificity of hK2. A phage-displayed random pentapeptide library with exhaustive diversity was generated and then screened with purified hK2. Phages displaying peptides susceptible to hK2 cleavage were amplified in eight rounds of selection and genes encoding substrates were transferred from the phage to a fluorescent system using cyan fluorescent protein (derived from green fluorescent protein) that enables rapid determination of specificity constants. This study shows that hK2 has a strict preference for Arg in the P1 position, which is further enhanced by a Ser in P'1 position. The scissile bonds identified by phage display substrate selection correspond to those of the natural biological substrates of hK2, which include protein C inhibitor, semenogelins, and fibronectin. Moreover, three new putative hK2 protein substrates, shown elsewhere to be involved in the biology of the cancer, have been identified thus reinforcing the importance of hK2 in prostate cancer development.

Programa de promoción de la salud bucodental + propuesta didáctica : Aprende a sonreír

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales / Ciudadanía / Salud Pública / .Esta publicación es una actualización de los contenidos de la "Propuesta didáctica. Promoción de la salud bucodental en el ámbito escolar. Programa Aprende a sonreír" (2003)

Appropriation of technology in "non-western" societies: an approximation to the case of Bulgaria

The principal focus of the PhD thesis lies in the Social Software area and the appropriation of technology in "non-Western" societies taking the example of Bulgaria. The term "non-Western" is used to explain places considered technologically underdeveloped. The aims have been to capture how Bulgarian users creatively interpret and appropriate Internet identifying the sociocultural, political and subjective conditions in which that appropriation occurs, to identify emerging practices based on the interpretation and use of Internet and the impact they had on society and what conditions could influence the technological interpretation and the meaning these practices had for both users and social configuration of Internet as media in Bulgaria. An ethnographic approach has been used simultaneously in different online and offline contexts. On the one hand, this study is based on exploration of the Bulgarian Internet Space through online participant observation in forums and websites reviews and on the other hand, on semi-structured interviews with different types of users of the virtual platforms found, made both face to face and online and finally online participant observation at the same platforms. It is based on some contributions of the ethnographic work of Christine Hine in virtual environments and the notions of time and space of Barbara Czarniawska contextualized in the modern form of organization that occurs in a network of multiple and fragmented contexts across many movements.

Assisted reproductive technology and obstetric outcome in couples when the male partner has a chronic viral disease.

BACKGROUND Assisted reproductive technology (ART) with washed semen can achieve pregnancy with minimal risk of horizontal and vertical transmission of chronic viral diseases (CVD) such as human immunodeficiency virus (HIV), hepati- tis C virus (HCV) and hepatitis B virus (HBV) among serodiscordant couples. How- ever, few studies have been made of the use made by these couples of ARTs or of the obstetric results achieved. MATERIALS AND METHODS In this retrospective study, 93 men who were seropositive for HIV, HCV or HBV and who underwent assisted reproduction treatment at our centre (Hospital Universitario Virgen de las Nieves, Granada, Spain) were included. Washed semen was tested to detect viral particles. Non-infected women were tested before and after each treatment, as were the neonates at birth and after three months. RESULTS A total of 62 sperm samples were washed, and none were positive for the detec- tion of viral molecules. Semen samples from 34 HBV positive males were not washed since the female partner had immunity to hepatitis B. In total, 38 clinical pregnancies were achieved (22% per cycle and 40.9% per couple) out of 173 cycles initiated, and 28 births were achieved (16.2% per cycle and 30.1% per couple), producing 34 live births. The rate of multiple pregnancies was 21.4%. Obstetric and neonatal results were similar in the groups of couples studied. At follow-up, no seroconversion was detected in the women or neonates. CONCLUSION Sperm washing and intracytoplasmic sperm injection are shown to be a safe and effective option for reducing the risk of transmission or super infection in serodiscordant or concordant couples who wish to have a child. Pregnancies ob- tained by ART in couples when the male is CVD infected achieve good obstetric and neonatal results.

Experimental bacterial endocarditis after dental extractions in rats with periodontitis.

The development of bacterial endocarditis was analyzed after dental extractions in rats with or without periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars and placing the animals on a high sucrose diet for 14 weeks. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hr later the maxillary first molars were extracted. The animals were killed 72 hr after the extractions. In rats with periodontal disease, extractions resulted in a 48% (14 of 29) incidence of bacterial endocarditis, most cases of which were due to Streptococcus spp. (one was caused by Staphylococcus aureus). In contrast, when the teeth with a healthy periodontium were extracted, only 6% (one of 15) of the rats developed endocarditis. When catheters were placed in animals with periodontal disease but no extractions were performed, no endocarditis occurred.

Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis.

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

Openness and technology diffusion in payment

We study the relationship between openness and payment system development. In particular, we analyze how the existence of technology diffusion from a more developed country fosters a transformation of payment choice in a less developed country. We apply our analysis to Mexico. Economic growth in Mexico was not high enough to cause a transformation of payment choice observed in the data after 2001. We argue that the switch towards electronic payments can be attributed to openness and related payment technology spillovers from the US in the context of NAFTA.

Dental Phenotype in Jalili Syndrome Due to a c.1312 dupC Homozygous Mutation in the CNNM4 Gene.

Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy) and a dental disorder (amelogenesis imperfecta), which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a disrupted magnesium transport is involved in the development of the dental abnormalities observed in Jalili syndrome.

Report of Recommendations to the Information Technology Department, June 30, 2001

Annual Auditors report of Information Technology Department

Information Technology Department 2001 Annual Report, 2001

Annual report of Information Technology Department

Annual Report for Information Technology Department, 2000

Annual Report of Information Technology Department

Report of Recommendations to the Information Technology Department, June 30, 2002

State Agency Audit Report

Importance of databases for technology assessment.

The data indispensable for carrying out the comprehensive, multi-faceted process of medical technology assessment (MTA) should be collected from a variety of sources. The authors distinguish between type "A" general data, useful for assessment but collected without this specific aim, and type "B" data. Registries of health care procedures or of diseases, as well as clinical data bases are quoted as examples of type "B" data, specifically relating to MTA. Since demographic methods are of importance for the evaluation of long-term effects of medical technologies, examples of sources of type "A" data are presented. Their significance for health policy making is discussed.