Salmonella enterica Serovar Typhimurium Increases Functional PD-L1 Synergistically with Gamma Interferon in Intestinal Epithelial Cells via Salmonella Pathogenicity Island 2.

Nontyphoidal serovars of Salmonella enterica are pathogenic bacteria that are common causes of food poisoning. Whereas Salmonella mechanisms of host cell invasion, inflammation, and pathogenesis are mostly well established, a new possible mechanism of immune evasion is being uncovered. Programmed death ligand 1 (PD-L1) is an immunosuppressive membrane protein that binds to activated T cells via their PD-1 receptor and thereby halts their activation. PD-L1 expression plays an essential role in the immunological tolerance of self-antigens but is also exploited for immune evasion by pathogen-infected cells and cancer cells. Here, we show for the first time that Salmonella infection of intestinal epithelial cells causes the induction of PD-L1. The increased expression of PD-L1 through Salmonella infection was seen in both human and rat intestinal epithelial cell lines. We determined that cellular invasion by the bacteria is necessary for PD-L1 induction, potentially indicating that Salmonella strains are delivering mediators from inside the host cell that trigger the increased PD-L1 expression. Using knockout mutants, we determined that this effect largely originates from the Salmonella pathogenicity island 2. We also show for the first time in any cell type that Salmonella combined with gamma interferon (IFN-γ) causes a synergistic induction of PD-L1. Finally, we show that Salmonella plus IFN-γ induction of PD-L1 decreased the cytokine production of activated T cells. Understanding Salmonella immune evasion strategies could generate new therapeutic targets and help to manipulate PD-L1 expression in other diseases.

[Dietary behavior disorders: opinions and expectancies on prevention and treatment strategies from the perspective of the several social actors]. / Trastornos de la conducta alimentaria: opiniones y expectativas sobre estrategias de prevención y tratamiento desde la perspectiva de diferentes actores sociales.

AIMS: The prevalence increase of Eating Disorders in the last decades emphasizes the necessity to develop strategies from the public healthcare system which include the perspective of the principal implicated social actors. The present study aims to know their opinions and expectations regarding the prevention and treatment of Eating Disorders. METHODS: Realization of 5 focus groups (with relatives, adolescents, professionals from the health and educational sector, representatives from institutions and support groups) and 14 semi-structured interviews (with Eating Disorder patients and relatives) about strengths and weaknesses of actual prevention and treatment programs, expectations of change and suggestions for improvement. Analysis of contents and triangulation of results. RESULTS: The absence of resources and knowledge about Eating Disorders, the scarcity of transversal programs and insufficient coordination were named as the main weaknesses whereas interdisciplinary pilot programs were positively valued. As principal demands, major endowment of human and material resources, increased coverage of specialized services, promotion of specific training and improvement of coordination was asked for. Regarding prevention, preference toward an unspecific approach to the subject in order to hinder imitation between young people was highlighted. The care in Day Hospitals was considered one of the most appropriate treatment modalities for the characteristics of this disease being valued the potentially therapeutic effect of contact between Eating Disorder patients. The support network, the education field and the family were named as other important pillars in a multidisciplinary approach to the disease. There was also a demand for the development of combined programs. CONCLUSIONS: The discussion of different psychotherapeutic approaches, the role of support groups in the caring network as well as the post-hospital follow-up were identified as issues open to future research.

[Condom use among the young engaging in vaginal intercourse]. / Uso del profiláctico entre la juventud en sus relaciones de coito vaginal.

OBJECTIVE: To describe young people's use of condoms in penetrative vaginal intercourse, and to identify the factors associated with this use. METHOD: The information was collected using a self-administered questionnaire put in 1,000 people between 14 and 24 years of age resident in the region of Andalusia (Spain). The results of the sample were representative and the trust interval was 95%. A bivariante analysis was carried out and hierarchical logistic regression equations were adjusted to verify associations between the dependent variable use of the condom in the vaginal intercourse and the variables proposed from PRECEDE model (predisposing, enabling, and reinforcing). The adjustment of the model was of a 38%, according to the Nagelkerke's statistic. RESULTS: Of the people surveyed, 750 had affective and/or sexual relations with physical contact, and 63% of these had vaginal intercourse (47% of all surveyed). Of those, people that only had vaginal intercourse once (12% of all surveyed), 83% (10,3% of all surveyed) used a condom, whereas, people that had sex more than once (34% of all surveyed), 49% always used a condom (16,9% of all surveyed). The variables associated with always using a condom were: intention of safe behaviour with their regular partner and low frequency of practice. The variables associated with never using a condom were: living emancipated, having an external locus of control (thinking that becoming infected depends upon external factors), low number of zones of the body identified as pleasure-sensitive, thinking that a condom is not necessary if one trusts his or her partner, intention of unsafe behaviour with their regular partner, and not talking with the partner about preventive methods before having sex. DISCUSSION: The most associated factors with using or not a condom in vaginal intercourse are predisposing (attitudes, values and believes) that are related with the kind of sexual partner. Interventions (based on the young active participation) are suggested to make them perceived the compatibility between the trust with the partner and the use of condom, and put in doubt the false safety given by a partner perceived as habitual.

[Emotional climate and internal communication in a clinical management unit compared with two traditional hospital services]. / Clima emocional y comunicación interna en una unidad de gestión clínica y dos servicios hospitalarios tradicionales.

BACKGROUND AND OBJECTIVE: The aim of this study is to compare the emotional climate, quality of communication and performance indicators in a clinical management unit and two traditional hospital services. MATERIAL AND METHODS: Quantitative study. INSTRUMENT: questionnaire of 94 questions. PARTICIPANTS: 83 health professionals (63 responders) from the clinical management unit of breast pathology and the hospital services of medical oncology and radiation oncology. ANALYSIS: descriptive statistics, comparison of means, correlation and linear regression models. RESULTS: The clinical management unit reaches higher values compared with the hospital services about: performance indicators, emotional climate, internal communication and evaluation of the leadership. An important gap between existing and desired sources, channels, media and subjects of communication appear, in both clinical management unit and traditional services. CONCLUSIONS: The clinical management organization promotes better internal communication and interpersonal relations, leading to improved performance indicators.

[Opinions and expectations of patients with health problems associated to asbestos exposure]. / Opiniones y expectativas de pacientes con enfermedades relacionadas con la exposición al amianto.

BACKGROUND: The prevalence of diseases related to asbestos exposure requires the development of monitoring programs and specific health care protocols. The aim of this study is to determine the opinions and expectations of former workers of an asbestos factory, in order to adapt the care process to the needs of the affected population, and to learn about the activity of the association that represents them. METHODS: Qualitative study. Focus groups with former employees of a corrugated asbestos factory, members of the association AVIDA (Seville). Recording and transcription of interviews. Discourse analysis with Nudist Vivo 1.0. RESULTS: All respondents have health problems, including asbestosis, lung cancer and mesothelioma. Through the association, they are involved in an ongoing process of negotiation with the public administration, to improve healthcare, achieve recognition as having an occupational disease and the payment of compensation. The lack of monitoring and continuity in care is designated as the major problem in the current care process. They welcome the creation of special care units, the good treatment received and the quality of technical instruments in the public health system. On the contrary, they criticize the difficulties in finding an accurate diagnosis, the lack of continuity of care, and the bureaucratic difficulties and lack of specific care directed to affected relatives. The participants' expectations highlight their intention to participate in the development of future programs and protocols. CONCLUSIONS: This study confirms the multifactor nature of diseases related to asbestos exposure and the importance of determining the needs and demands of the affected population in order to improve health care.

[Patients' opinions and expectations about the dialysis care process]. / Análisis de calidad percibida y expectativas de pacientes en el proceso asistencial de diálisis.

BACKGROUND: To determine the experiences and needs of patients on dialysis, in order to identify critical points of the care process and develop proposals for improvement. METHODS: Qualitative study using semistructured interviews with 22 patients on hemodialysis and peritoneal dialysis, from the Andalusian Health Service. Discourse analysis, using the SERVQUAL model. Triangulation of results. RESULTS: The diagnostic stage is described as the hardest moment as it requires acceptance of the disease. During hemodialysis, we see both positive adaptation and the perception of a diminished quality of life. The technique of peritoneal dialysis is evaluated positively, enabling greater independence, despite requiring more responsibility for self care. The contact with patients' organizations or the provision of a counseling service are valued as an aid in the process. With respect to different dimensions of the SERVQUAL model, human treatment and professional competence are valued. The critical points are lack of coordination, malfunctioning of transportation and lack of transparency in the management of waiting lists. Shortcomings in dealing with informal caregivers and the level of knowledge of professionals from areas other than Nephrology, also appear as deficiencies. CONCLUSIONS: The main proposals for improving the dialysis process are: attention to psychosocial aspects, the improvement of organizational aspects such as transport, and greater attention to informal caregivers.

Area deprivation and mortality in the provincial capital cities of Andalusia and Catalonia (Spain).

OBJECTIVE: To study the linkage between material deprivation and mortality from all causes, for men and women separately, in the capital cities of the provinces in Andalusia and Catalonia (Spain). METHODS: A small-area ecological study was devised using the census section as the unit for analysis. 188,983 Deaths occurring in the capital cities of the Andalusian provinces and 109,478 deaths recorded in the Catalan capital cities were examined. Principal components factorial analysis was used to devise a material deprivation index comprising the percentage of manual labourers, unemployment and illiteracy. A hierarchical Bayesian model was used to study the relationship between mortality and area deprivation. MAIN RESULTS: In most cities, results show an increased male mortality risk in the most deprived areas in relation to the least depressed. In Andalusia, the relative risks between the highest and lowest deprivation decile ranged from 1.24 (Malaga) to 1.40 (Granada), with 95% credibility intervals showing a significant excess risk. In Catalonia, relative risks ranged between 1.08 (Girona) and 1.50 (Tarragona). No evidence was found for an excess of female mortality in most deprived areas in either of the autonomous communities. CONCLUSIONS: Within cities, gender-related differences were revealed when deprivation was correlated geographically with mortality rates. These differences were found from an ecological perspective. Further research is needed in order to validate these results from an individual approach. The idea to be analysed is to identify those factors that explain these differences at an individual level.

Biotechnological applications of green fluorescent protein.

Since its first use as a reporter gene in 1994, green fluorescent protein (GFP) has served as the researcher's agent: slipping, virtually undetected, into unseen spaces, reporting back valuable information, and securing the delivery of precious cargo through hostile domains. GFP's strength lies in its small size, formidable stability, and relative ease of use. It requires only oxygen and an energy source to do its work, which can be supplied at low cost and high precision, respectively. With such a low threshold for use, GFP is often the first line of inquiry into an unknown space. Here is provided a brief compendium of GFP's contributions to biotechnology. They are linked by a need for a level of information that was previously inaccessible, both spatially and temporally. Protein fusions, transcriptional reporters, whole-organism visualization, and various other screening applications are reviewed with respect to biotechnological applications. Germane molecular improvements to GFP are also discussed.

[Professionals and managers on internal communication in the Program of Mother-Child Health of Andalucia. Evaluation Team of the PSMI]. / Profesionales y gestores ante la comunicación interna en el Programa de Salud Maternoinfantil de Andalucía. Equipo de Evaluación del PSMI.

OBJECTIVE: To find the views of primary health area directors and of professionals in health centres (HC) in Andalusia on internal communication within the Mother-Child Health Programme introduced in this autonomous community. DESIGN: Descriptive study that uses qualitative and quantitative methodology. SETTING: Primary care (PC) areas and HC in Andalusia, between July 1994 and February 1995. PARTICIPANTS: 51 PC area directors and 91 HC professionals. MEASUREMENTS AND MAIN RESULTS: Self-administered questionnaire (directors) and focus groups (professionals) were used. Analysis by non-parametric tests compared averages and analysed discourse contents. Internal communication was an important weakness in the Mother-Child Health Programme and in PC in general. There were important differences between the perceptions of directors and professionals in relation to the guidelines of the Mother-Child Programme. As such, in all the area administrations it was affirmed that there were programme objectives agreed with the professionals, and transmission channels for these objectives between the area and the centres, although these were transmitted in writing in under 25% of the areas. However, professionals thought that the objectives and guidelines of the programme were unclear and ill-defined. In addition, the view that the annual objectives are not negotiated was quite common. CONCLUSIONS: Internal communication in PC is a considerable weakness in HC management. The professionals perceive considerable conflicts of interest between them and the organisation's directors.

Drug synergy in experimental African trypanosomiasis.

The possibilities of trypanocidal drug synergy have been examined in vitro and in vivo using a monomorphic laboratory strain of Trypanosoma rhodesiense. Twenty-seven different drug pair combinations were chosen from among 12 representative trypanocides on the basis of surmized or reported synergy, evidence of collateral sensitivity in resistant strains, and known differences in modes of action or in field use. In vitro synergy test were made with a transfer plate technique which allows direct isobol determination by microtest tray superimposition. All pairs showing synergy in vitro were tested further in mice. Statistically significant synergy was shown only by suramin and tryparsamide, suramin and Puromycin, and suramin and Berenil. Although six other pairs, of which three contained suramin, showed higher than addictive cure rates, these rates fell short of statistical significance.

Expression of an anaplerotic enzyme, pyruvate carboxylase, improves recombinant protein production in Escherichia coli.

Anaplerotic enzyme reactions are those which replenish tricarboxylic acid intermediates that are withdrawn for the synthesis of biomass. In this study, we examined recombinant protein production in Escherichia coli containing activity in an additional anaplerotic enzyme, pyruvate carboxylase. In batch fermentations, the presence of pyruvate carboxylase resulted in 68% greater production of the model protein, beta-galactosidase, 41% greater cell yield, and 57% lower acetate concentration. We discuss why these results indicate that acetate concentration does not limit cell growth and protein synthesis, as predicted by other researchers, and suggest instead that the rate of acetate formation represents an inefficient consumption of glucose carbon, which is reduced by the presence of pyruvate carboxylase.

Protective immunity to malaria. Studies with cloned lines of Plasmodium chabaudi chabaudi and P. berghei in CBA/Ca mice. II. The effectiveness and inter- or intra-species specificity of the passive transfer of immunity with serum.

Serum was obtained from CBA/Ca mice infected, reinfected or superinfected with parasites taken one or two syringe passages from cryopreserved reference stabilates derived from cloned lines of the AS or CB isolates of P.c. chabaudi. Serum was also collected from mice superinfected with parasites derived from a cloned line of P. berghei KSP-11. When injected into normal syngeneic recipients subsequently challenged with homologous or heterologous parasites, these sera mediated some or all of the following modifications to the breakthrough parasitaemias which invariably occurred (i) an extension of the pre-patent period (ii) an extension of the time taken for the parasitaemia to reach 2% (iii) a reduction of peak parasitaemia (iv) protraction of the initial peak of parasitaemia. These modifications were particularly evident with serum from superinfected mice and to a lesser extent with serum from animals reinfected once after recovery from a primary infection. Serum taken during the course of such a primary infection produced extended pre-2% periods, other effects being only marginal. Serum mediated modifications produced by reinfection and superinfection serum appeared largely species-specific with a limited degree of cross-reactivity. Intraspecific specificity was also apparent with serum from P.c. chabaudi AS or CB reinfected or superinfected mice, although marginal cross-immunity was again observed. When analysed by the fluorescent antibody technique on smears of methanol fixed parasitized erythrocytes, reinfection and superinfection sera were almost totally cross-reactive both within and across species. Preliminary evidence that parasites breaking through the effects of these sera may constitute a phenotypic antigenic variant is presented and possible mechanisms for the parasitaemia modifying effects of the various sera discussed.

[The attitudes of primary care physicians towards the opening of health centers]. / Actitudes de los médicos de atención primaria hacia la puesta en marcha de los centros de salud.

OBJECTIVE: To measure doctors' attitudes to the opening of Health Centres. DESIGN: Descriptive study. SITE. Primary Care services on the island of Gran Canaria. PARTICIPANTS: Doctors with tenure. MAIN MEASUREMENTS AND RESULTS: From a self-administered Likert type questionnaire, it could be observed that the proportion of those polled who did not reply was linked to the number who had a "Fiscal Licence" (Odds Ratio O.R. = 6.26), a ratio which did not disappear when stratified by age (O.R. = 5.88 for those less than or equal to 40 and O.R. = 3.08 for those greater than 40). The scale presented high internal consistency (Cronbach alpha 0.937), indicating favorable attitudes from doctors integrated into Health Centres and both positive and negative attitudes in doctors of a traditional cut. Those specialising in Family Medicine, those under 40 years old, those who had no other health job and those connected with Trades Unions showed more favorable attitudes. CONCLUSIONS: Individual and group characteristics are linked to different attitudes. The knowledge, evaluation and behaviour components of doctor's attitudes must be improved, by involving the reference groups of both individuals and groups.

[Motivation and incentives: different perceptions of administrators and professionals. Evaluation Team of the Materno-Infantile Health Program]. / Motivación e incentivos: percepciones diferentes de gestores y profesionales. Equipo de Evaluación del Programa de Salud Materno-Infantil (PSMI).

OBJECTIVE: To find the views of Primary Care District managers and Health Centre (HC) professionals in Andalusia on systems of motivation and incentive in use in this autonomous community. DESIGN: A descriptive study which uses qualitative and quantitative methodology. SETTING: Primary Care districts and Health Centres in Andalusia. PARTICIPANTS: Primary Care district managers (51) and HC professionals (91). MATERIAL AND METHODS: Information-gathering: self-administered questionnaire (managers) and focus groups (professionals). ANALYTICAL TECHNIQUES: Non-parametric tests to compare means and analysis of contents of discourse. Field-work. July 1994 and February 1995. RESULTS: 55% of the district managers thought that the incentive systems in use were inadequate and insufficient. Enabling professionals to be trained is the main motivating and incentive mechanism in place. Variable productivity was the next most common mechanism. However, variable productivity, in the view of the professionals, was the main demotivating factor of recent years. Professionals thought that the economic rewards of the incentives system were slight, the target variables were unsuitable, there were no objective evaluation mechanisms and the economic differences between the incentives earned by managers and professionals were too great. CONCLUSIONS: The District managers indicated that improvements in the incentives systems used are needed. The HC professionals affirmed that the Andalusian incentives system has demotivated Primary Care teams and has had little effect on orienting professional practice.