Research ethics oversight in Norway: structure, function, and challenges.

BACKGROUND: While the development and evaluation of clinical ethics services in Norway has been recognized internationally, the country's research ethics infrastructure at times may have been less well developed. In 2016, media interest in the controversial nature of some health services research and pilot studies highlighted gaps in the system with certain types of research having no clear mechanisms through which they may be given due independent consideration. It is not clear that new legislation, implemented in 2017, will address this problem. We explore relevant law, committee scope, and the function of the system. We show that 1) Norwegian law provides for ethics assessment for all forms of health research; 2) regional RECs in Norway might not have always enforced this provision, considering some interventional health services research to be outside their remit; and 3) Norwegian law does not explicity provide for local/university RECs, meaning that, in practice, there may be no readily accessible mechanisms for the assessment of research that is excluded by regional RECs. This may include health services research, pilot studies, and undergraduate research. New 2017 legislation has no effect on this specifically but focuses on institutions regulating researcher activity. This may place researchers in the difficult situation of on one hand, needing to hold to recognized ethical standards, while on the other, not readily having access to independent committee scrutiny to facilitate consistent operation with these standards. CONCLUSION: To support researchers in Norway and to protect the public, it may be necessary either to widen the regional RECs' remit or to make legislative alterations that permit and do not discourage the existence of local RECs.

Concordancia de antígenos de dengue en el ELISA de captura de IgM (MAC ELISA) en el IICS-UNA / Concordance of dengue antigens M antibody-capture ELISA (MAC ELISA) in the IICS-UNA

El dengue es una enfermedad aguda grave considerada actualmente como infección reemergente, cuyo vector principal es el Aedes aegypti. En Paraguay en el 2007 fueron reportados 28.181 casos, 55 se clasificaron como fiebre hemorrágica del dengue de los cuales 7 fallecieron. El 90% de los casos fueron de Asunción y del Departamento Central,10% del resto del país. En los últimos años se han desarrollado diferentes sistemas inmunoenzimáticos para el diagnóstico del dengue, entre ellos el ELISA de captura de IgM (MAC ELISA). El objetivo de este estudio observacional analítico de corte transverso fu ecomparar la prueba del MAC ELISA desarrollada en el Instituto de Investigaciones en Ciencias de la Salud (IICS) utilizando antígenos suministrados por el Instituto Pedro Kouri(IPK) de Cuba y el Evandro Chagas de Brasil, con el kit comercial ELISA IgM por capturapara virus del dengue (Focus Diagnostics Inc. Cypress, CA, USA). Fueron seleccionados alazar 92 sueros de pacientes codificados que concurrieron al IICS con sospecha de dengue, respetándose la confidencialidad de los mismos. La concordancia obtenida fue del94.6% (Índice Kappa: 0.891) utilizando el antígeno del IPK y 96.7% (Índice Kappa:0.9350) con el antígeno del Evandro Chagas, mostrándose alta significancia estadística(p<0.00001) en ambos casos. La excelente concordancia obtenida con los dos antígenos indica que los mismos pueden ser utilizados indistintamente en la prueba del MAC ELISA desarrollada en el IICS, a fin de apoyar el diagnóstico del dengue a menor costo y quesería de producción local.

Dengue is an acute disease currently considered a re-emerging infection, whose main vector is Aedes aegypti. In 2007, 28,181 cases were reported in Paraguay, 55 were classified as dengue hemorrhagic fever and seven of them died. Ninety percent of the cases were from Asunción and the Central Department and the remaining 10% from the rest of the country. In recent years various immunoenzymatic systems have been developed immunoassay for the diagnosis of dengue, including the M antibody captureELISA (MAC ELISA). The aim of this cross-sectional observational study was to compare the MAC ELISA test developed at the Instituto de Investigaciones en Cienciad de la Salud(IICS) using antigens supplied by the Instituto Pedro Kouri (IPK) of Cuba and Evandro Chagas of Brazil with a commercial kit of M antibody capture ELISA for dengue virus (Focus Diagnostics Inc. Cypress, CA, USA). Ninety two coded serum samples wererandomly selected from patients who attended the IICS with suspected dengue, respecting their confidentiality. The concordance obtained was 94.6% (Kappa Index: 0.891) using the IPK antigen and 96.7% (Kappa index: 0.9350) with the antigen from Evandro Chagas showing high statistical significance (p<0.00001) in both cases. The excellent concordance obtained with the two antigens indicates that they can be used indistinctly in the MAC ELISA test developed in the IICS to support the diagnosis of dengue at a lower cost and would be locally produced.

Concordancia entre las pruebas de ELISA avidez IgG desarrollados en el Instituto de Investigaciones en Ciencias de la Salud y un ELISA avidez comercial / Concordance between the IgG avidity ELISA tests developed at the Instituto de Investigaciones en Ciencias de la Salud and a commercial avidity ELISA

La infección aguda de toxoplasmosis en la mujer durante el embarazo en su mayor parte es asintomática y detectable solo por anticuerpos lo que podría afectar severamenteal feto si no es diagnosticada y tratada precozmente. En este estudio observacionalanalítico de corte transverso se comparó la prueba de ELISA Avidez IgG paratoxoplasmosis desarrollado en el Instituto de Investigaciones en Ciencias de la Salud(IICS) con un test comercial de avidez InmunoLISA Organics USA. Para la concordanciase utilizó 41 sueros mantenidos a -20 ºC procedentes de la seroteca del Departamento de Producción-Bioquímica seleccionados al azar. La concordancia obtenida fue de 92.7% y un índice de Kappa de 0.820 con IC95% (0.6-1) y p<0.0001. El índice bajo de avidez sugiere una infección aguda pero para el diagnóstico debería estar acompañado de otras pruebas serológicas y la clínica del paciente. En cambio un índice alto es diagnóstico de una infección crónica.

The acute infection caused by Toxoplasma gondii in pregnant women is mostly asymptomatic and detectable only by antibodies that could severely affect the fetus if the infection is not diagnosed and treated precociously. In this cross-sectional observational,the analytical the IgG avidity ELISA test for toxoplasmosis, developed at the Instituto de Investigaciones en Ciencias de la Salud (IICS), was compared to a commercial avidity kit InmunoLISA (Organics, USA). For the concordance, 41 serum samples kept at -20ºC atthe Department of Production-Biochemistry of IICS were tested. The concordance obtained was 92.7% and a Kappa index of 0.820 with IC95% (0.6-1) and p <0.0001. The low avidity index suggests an acute infection but for diagnosis this result should beaccompanied by other serologic tests and clinical symptoms. Instead, a high avidity index suggests a chronic infection.

Mantenimiento y titulación del virus de dengue para obtención de antígeno viral / Maintenance and titration of dengue virus for the obtainment of viral antigens

El dengue es un grave problema de salud pública que no posee vacuna ni tratamiento específico. El método de diagnóstico más utilizado es el serológico, específicamente, la detección de anticuerpos IgM anti-dengue. Los antígenos virales utilizados en este método pueden ser preparados en cultivo de células de Aedes albopictus (C6/36). El objetivo de este trabajo fue el mantenimiento de los cuatro serotipos virales (D1 (RIO), D2 (RIO), D3 (H-87), D4 (BV)) en células C6/36 para la futura preparación de antígenos virales. Las células C6/36 fueron cultivadas en medio L-15 con 10% de SFB a 28ºC, e infectadas con 50 ml de cada uno de los serotipos virales por 5 a 7 días. Una vez confirmada la infección por inmunoflurescencia indirecta, los virus fueron titulados por la técnica de placa de lisis. Los títulos de los serotipos fueron D1 (RIO) (2,9 x 106 PFU/ml), D2 (RIO) (4,4 x107 PFU/ml), D3 (H87) (6,4 x 107 PFU/ml) y D4 (BV) (5,1 x106 PFU/ml). La producción de antígenos virales es de gran importancia dado que los mismos pueden ser utilizados en diversos métodos diagnósticos.

Dengue is a serious public health problem that has neither vaccine nor specific treatment. Serology is the most frequently used diagnosis method, specifically the anti-dengue IgM detection. The viral antigens employed in this method could be prepared from Aedes albopictus cell cultures (C6/36). The objective of this study was to maintain the four viral serotypes (D1 (RIO), D2 (RIO), D3 (H-87), D4 (BV)) on C6/36 cells for the preparation of viral antigen in the future. The C6/36 cells were cultured in L-15 medium supplemented with 10% FCS, infected with 50 µl of each viral serotype and then incubated for 5-7 days at 28°C. After confirmation of the infection by indirect immunofluorescence (IIF), viral titration was performed by lysis plaque assay. The serotypes titres obtained were as follows: [2.9 x 106 PFU/ml] for D1 (RIO), (4.4 x107 PFU/ml) for D2 (RIO), (6.4 x 10 7 PFU/ml) for D3 (H87) and (5.1 x106 PFU/ml) for D4 (BV). The production of viral antigens is very important because they could be used in several diagnosis methods.

Estudio de Fiebre Amarilla en primates en áreas de brote de los departamentos de San Pedro y Central del Paraguay / Study of Yellow Fever in primates in outbreaks areas of the departments of San Pedro and Central in Paraguay

La Fiebre Amarilla (FA) es una de las más importantes zoonosis que afecta a poblaciones humanas. La FA silvestre es imposible de ser erradicada, manteniéndose activa en zonas tropicales en África y Sudamérica. Todas las especies de primates son susceptibles y se consideran reservorios en el medio silvestre. La mortalidad es baja, se desconoce su valor con precisión, sin embargo existen epizootias con alta mortalidad, en humanos varía entre 20-50%. El objetivo de este trabajo fue buscar evidencias de FA en primates capturados en áreas de brote de FA de los departamentos de San Pedro y Central del Paraguay mediante la técnica de Neutralización por reducción de placas para FA cepa vacunal 17 D. Los resultados en los 35 primates estudiados fueron negativos, quizás por lo tardío del momento en la toma de muestras y bajo número de primates capturados.

Yellow Fever (YF) is one of the most important zoonotic diseases affecting human population. It is impossible to eradicate wild YF remaining active in tropical zones of Africa and South America. All species of primates are susceptible and are considered reservoirs in wild regions. Mortality is low and its precise value is unknown though there are epizootics with high mortality rates and in humans varies between 20-50%. The objective of this study was to search for evidence of YF in primates caught in YF outbreaks areas of the departments of San Pedro and Central in Paraguay through the neutralization technique by plates reduction for YF vaccine strain 17 D. The results in the 35 primates studied were negative, perhaps because of the lateness of the time sampling and the low number of captured primates.

Seguimiento clínico y serológico de pacientes tratados de leishmaniosis cutánea / Clinical and serological follow-up of patients treated from cutaneous

La inmunofluorescencia indirecta con antígeno crudo de Leishmania constituye una técnicaserológica convencional que para el diagnóstico de leishmaniosis presenta una sensibilidadmoderada, entre el 70 y el 80%. Son muy raros los trabajos que en la literatura reportan su usopara el seguimiento serológico post-tratamiento de los pacientes, aunque la experiencia que engeneral se tiene en áreas endémicas consiste en que la mayoría de los casos clínicamente curadospresentan una disminución importante de los títulos serológicos con el avance del tiempo. Estetrabajo tiene por objetivo describir el cuadro clínico y los valores de la reacción serológica enpacientes con leishmaniosis cutánea antes y después de su tratamiento. Para este trabajo ha sidoestudiado el comportamiento clínico y serológico de un grupo de 32 pacientes con leishmaniosiscutánea, en un brote de la enfermedad producido en 1998 en el distrito de Capiibary,Departamento de San Pedro. De los pacientes evaluados hasta 18 o 24 meses post-tratamientotodos excepto uno manifestaron curación de sus lesiones. La gran mayoría de los sujetos hanmostrado disminución de los títulos serológicos, hasta la negativización. Se concluye que elseguimiento serológico arroja valores que coinciden con la clínica de los pacientes, por lo tantoamerita que sea llevado a cabo complementariamente con la inspección clínica. Al no contar en esteestudio con casos de reactivación cutánea o mucosa, no se puede concluir acerca del valorpredictivo de la serología para estos casos

Leishmaniasis tegumentaria: sensibilidad de la inmunofluorescencia indirecta en pacientes con diagnótico parasitológico / Tegumentary leishmaniasis: sensitivity of the indirect immunofluorescent assay in patients with parasitológical diagnosis

La leishmaniasis tegumentaria es una zoonosis endémica de zonas tropicales y subtropicales del mundo, de difícil diagnóstico laboratorial. En áreas endémicas se realiza el diagnóstico de presunción basado en la presentación clínica y la reactividad a la prueba cutánea de la leishmanina. Sin embargo, un diagnóstico definitivo de la enfermedad requiere la combinación de diferentes métodos, entre los cuales la inmunofluorescencia indirecta (IFI) es uno de los más utilizados. Para determinar la sensibilidad de la IFI, se sometió un total de 95 pacientes con lesiones comprobadas de leishmaniasis a las pruebas de leishmanina, biopsia histopatológica, cultivo e IFI. En 80 pacientes se logró el diagnóstico parasitológico a través de la histopatología y/o el cultivo. De ellos, 58 muestras (72,5%) dieron reacción positiva en la IFI para Leishmania, aunque 12 de ellas (21%) también mostraron serología positiva para enfermedad de Chagas. La sensibilidad de la IFI para los casos de leishmaniasis mucosa solamente fue 81,3% (n=16). Se concluye que la IFI es un método de moderada sensibilidad para el diagnóstico de leishmaniasis tegumentaria.

Tegumentary leishmaniasis is an endemic zoonosis of tropical and subtropical areas of the world. Diagnosis of this illness is difficult even using laboratorial methods. In endemics areas a presumptive diagnosis is carried out based on the clinical presentation and reactivity to the skin test. However, a definitive diagnosis of the illness requires the combination of different methods, such as the indirect immunofluorescence assay (IIF), one of the most used methods. In order to determine the sensitivity of the IIF, a total of 95 patients with proven lesions of leishmaniasis were subjected to skin test, histopathology, culture and IIF. Parasitological diagnosis was achieved in 80 patients through histopathology and/or culture. Fifty­eight samples of them (72.5%) gave positive reaction by the IIF although 12 of them (21%) also showed positive serology for Chagas disease. The sensitivity of the IIF for mucosal leishmaniasis only was 81.3% (n=16). We concluded that IIF has moderate sensitivity for the diagnosis of tegumentary leishmaniasis.

The frequency of silencing in Arabidopsis thaliana varies highly between progeny of siblings and can be influenced by environmental factors.

In a collection of 111 transgenic Arabidopsis thaliana lines, silencing of the nptII gene was observed in 62 (56%) of the lines and three distinct nptII-silencing phenotypes were identified. Two T-DNA constructs were used, which differed in distance and orientation of the marker gene relative to the border sequences. Comparison of the sets of lines generated with each vector, indicate that the T-DNA construct configuration influence the incidence of lines displaying silencing, as well as the distribution of silencing phenotypes. Twenty lines were investigated more thoroughly. The frequency of silencing varied between siblings in 19 lines, including three lines containing a single T-DNA copy. The last line showed 100% silencing. The gus gene present in both constructs could be expressed in the presence of a silenced nptII gene. Investigation of methylation at a single site in the pnos promoter revealed partial methylation in multi-copy lines, but no methylation in single-copy lines. For 16 lines, the overall frequencies of silencing differed significantly between control plants and plants exposed to temperature stress; in 11 of these lines at the 0.1% level. In several cases, the frequency of silencing in progeny of stress-treated plants was higher than for the control group, while other lines showed higher frequencies of kanamycin-resistant progeny for the stress-treated sibling plants.

Antipsychotic drugs and obesity: is prolactin involved?

OBJECTIVES: To correlate the anthropometric indexes (Body Mass Index [BMI] and Waist-Hip ratio [WHR]) with the serum prolactin levels in a heterogeneous population of patients treated with typical antipsychotic (AP) drugs. METHODS: We evaluated BMI, WHR, and fasting serum prolactin of inpatients (n = 105) and outpatients (n = 122) treated with APs, in outpatients receiving other psychotropic drugs (OPDs) (n = 77), and in drug-free subjects (n = 33). Outpatients had free access to food, whereas the inpatient sample comprised people with a monotonous diet of approximately 2000 Kcal daily. RESULTS: Prolactin correlated positively with the BMI in the whole group of AP-treated outpatient men (P = 0.03) and with the WHR in AP-treated inpatient men (P = 0.053). Regarding treatment duration, prolactin and BMI correlated positively in men consecutively treated for more than 1 year (P = 0.023). By contrast, a trend toward a negative correlation between prolactin and BMI was observed in AP-treated outpatient women (P = 0.08). No significant correlation, or even a trend, was observed in the other groups. CONCLUSIONS: Prolactin may be involved in AP-induced weight gain, particularly in men. Future studies should characterize the period of maximal prolactin impact on body weight during AP treatment. Specific populations particularly sensitive to hyperprolactinemia might be identified as well. The negative correlation between prolactin and BMI detected in AP-treated women resembles the dampened prolactin response observed in severe primary obesity.

Evaluation of a simple screening test for the quality of drinking water systems.

A simple and inexpensive assay for detection of H2S producing bacteria in drinking water was evaluated in Paraguay. Using an improved preparation procedure, results were basically temperature independent in the range of 22-37 degrees C and correlated well with the presence of total coliform bacteria (96%, 28 degrees C). The assay was not suitable for control of surface water and dug well water due to the frequent presence of non-faecal coliforms. However, it was very suitable for routine control of high quality water systems, like treated community water systems or deep-tube well water, where complete absence of coliforms is required. The H2S-test is very inexpensive and does not require a laboratory technician or special equipment. Its use permits a cost-effective routine control of high quality community water systems in developing countries. In addition, this test turned out to be an effective educational tool for heightening the awareness of people towards dangers of unclean drinking water.