Antigenic and genomic relation between human influenza viruses that circulated in Argentina in the period 1995-1999 and the corresponding vaccine components.

BACKGROUND: The analysis of epidemic influenza virus has been focused on antigenic and genomic characterization of the hemagglutinin (HA) glycoprotein in order to detect new variants for the recommendation of the vaccine strains in each season. Since October 1998, WHO organized a second meeting to evaluate the vaccine formula for the southern hemisphere. OBJECTIVES: (a) Present the antigenic and genomic characterization of influenza strains obtained from the Argentina surveillance network, (b) compare between strains collected in Argentina and other countries with the vaccine formula strains used in each season. STUDY DESIGN: Influenza strains were collected during a 5-year period (1995-1999). Initially, laboratory diagnosis was done by immunofluorescence (IF) assay on clinical samples, followed by viral isolation in Madin-Darby canine kidney (MDCK) cells. The isolates were characterized antigenically by hemagglutination-inhibition (HI) assay with post-infection ferret antisera. The genomic characterization consisted on RT-PCR followed by sequencing of the HA1 portion of the HA gene. The comparison between reference and circulating strains was analyzed by the construction of phylogenetic trees. RESULTS: The H3N2 circulating strains matched the corresponding vaccine component only in 1999, the first year when a vaccine recommended specifically for the southern hemisphere was used. Besides, H1N1 circulating strains matched the corresponding vaccine component only in 1998. Regarding to influenza B, only in 1995, the circulating strains showed no match to the B vaccine component. CONCLUSIONS: The results showed the usefulness of an intensified influenza laboratory surveillance to access the correct vaccine and the importance of having the necessary tools to characterize the circulating strains.     

Premenstrual dysphoric disorder and changes in frontal alpha asymmetry.

OBJECTIVE: Since the clinical picture of premenstrual dysphoric disorder (PMDD) in the Luteal phase of the menstrual cycle is characterized by extreme negative affect, we predicted and obtained a change in frontal cortical EEG alpha asymmetry, which has been shown to be an index of affect. METHOD: We observed two monthly cycles for five women diagnosed as having PMDD and one monthly cycle for five non-PMDD control subjects. RESULTS: Asymmetry percent scores for the five PMDD women, and for the five control subjects before and after the Luteal phase were typically within the normal non-depressed range, however the asymmetry scores for the PMDD group fell into the negative range during the Luteal period while the control subjects remained stable. DISCUSSION: We predicted alpha asymmetry scores would be affected by the luteal phase in PMDD cases. This hypothesis was clearly confirmed.     

A critical analysis of commercially available latex particle reagents for C-reactive protein (CRP) slide agglutination tests

C-reactive protein (CRP) was assessed in pediatric serum samples using different commercial latex reagents, which were analyzed for species origin of the coating antibodies, homogeneity and density of the latex particles, and prozone agglutinating capacity. All reagents correctly agglutinated the positive and negative control sera. The antibodies coating the particles differed with regard to species origin: one was coated with rabbit, one with horse and goat, one with horse, goat, rabbit and swine, while the reference reagent had horse, goat and rabbit antibodies.Only the monospecies specific antibody-coated latex showed obvious prozoning; this reagent also had the smallest and most homogenous latex particles and showed the most clear-cut reactions. False agglutination was observed at 7–26% according to quantitation with the spot immunoprecipitate assay, which compared favorably with radial immunodiffusion measurements. The lowest percentage of false readings was noted for the rabbit antibody-coated particles; the highest for the reagent with particles coated using antibodies from 4 different species.No reagent had satisfactory precision for the low positive sera between 10 and 40 mg CRP/1.     

Fine-needle biopsy of the pancreas: Results of 204 routinely performed biopsies in 190 patients

Two-hundred and four fine-needle aspiration biopsies of the pancreas have been performed in 190 patients during a 12-year period. Sixty-one of these were performed percutaneously guided by endoscopic retrograde cholangio-pancreatography, percutaneous transhepatic cholangiography, angiography, or ultrasonography; and 143 were taken intraoperatively. In 77 (67%) out of 115 patients with pancreatic cancer, a correct cytological diagnosis was obtained. Two biopsies were reported as malignant in 1 patient who ultimately was found to have chronic pancreatitis (false positives). The frequency of not representative biopsies varied from 20.8% in patients with suspected cancer biopsied intraoperatively to 48.4% in patients biopsied preoperatively. A correct cytological diagnosis of malignancy was obtained preoperatively in 54.6% of patients with cancer, in 60.0% of patients evaluated without later operation, and in 71.1% of patients biopsied during laparotomy for suspected pancreatic cancer. The overall false-negative rate was 9.8%. The predictive value of a positive test was almost 100%, whereas the predictive value of a negative test was only 69.6% (total material). Analyses may indicate that a more aggressive approach with multiple punctures may lower the not representative biopsy rate and increase the diagnostic accuracy in patients with pancreatic cancer.

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Resumen Doscientas y cuatro biopsias pancreáticas por aspiración con aguja fina han sido realizadas en 190 pacientes en un período de 12 años. Sesenta y una de éstas fueron realizadas por vía percutánea guiada por colangiopancreatografía endoscópica retrógrada, colangiografía percutánea transhepática, angiografía, o ultrasonografía, y 143 fueron intraoperatorias. En 77 (67%) de 115 pacientes con cáncer del páncreas se obtuvo un diagnóstico citológico correcto. Dos biopsias fueron informadas como malignas en un paciente en quien finalmente se demostró pancreatitis crónica (falsas positivas). La frecuencia de biopsias no representativas varió entre 20.8% en pacientes con sospecha de cáncer y biopsia realizada intraoperatoriamente, a 48.4% en pacientes con biopsias realizadas en la fase preoperatoria. El diagnóstico citológico correcto de malignidad fue logrado preoperatoriamente en 54.6% de los pacientes con cáncer, en el 60.0% de los pacientes evaluados y sin operación posterior y en el 71.1% de los pacientes en quienes se realizó biopsia durante la laparotomía por sospecha de cáncer pancreático. La tasa global de resultados falsos negativos fue de 9.8%. El valor de predicción de una prueba positiva fue de casi 100%, mientras el valor de predicción de una prueba negativa fue de sólo 69.6% (material total). La implicación práctica de esto es que cuando se obtenga un resultado negativo se debe proceder con la toma de nuevas biopsias. En conclusión, creemos que la biopsia del páncreas con aguja fina es un procedimiento seguro que puede ser recomendado en todas las fases del proceso diagnóstico o terapéutico de lesiones pancreáticas, y que es valioso en la planeación de la terapia en pacientes con cáncer. Sinembargo, las biopsias negativas en casos de sospecha clínica de cáncer no siempre excluyen su presencia. Mayor análisis puede indicar que una actitud más agresiva, con punciones mÚltiples, puede disminuir la tasa de biopsias no representativas y aumentar la precisión diagnóstica en pacientes con cáncer pancreático.

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Résumé Deux cent quatre biopsies-aspirations à l'aiguille fine du pancréas ont été pratiquées chez 190 sujets au cours d'une période de 12 ans. Soixante et une d'entre elles ont été pratiquées par voie souscutanée en étant guidées par cathétérisme rétrograde, cholangiographie transpariétale, angiographie ou ultrasonographie et 143 ont été effectuées au cours de l'intervention. Chez 77 (67%) sujets appartenant à une série de 115 malades atteints de cancer du pancréas le diagnostic cytologique exact a été porté. Deux biopsies en faveur du diagnostic de cancer répondaient en réalité à des lésions de pancréatite chronique (faux positifs). La fréquence des biopsies ininterprétables chez les sujets suspects de cancer a varié de 20.8% lorsque l'examen a été pratiqué au cours de l'intervention à 48.4% lorsque ce mÊme examen a été effectué avant l'opération. Le taux de diagnostic cytologique exact de cancer a été respectivement de 54.6%, de 60.0% et 71.1% selon que la biopsie cytologique a l'aiguille a été pratiquée avant l'intervention, après un certain délai et au cours de l'opération. Au total, le taux des faux positifs s'est élevé à 9.8%. La fiabilité de la biopsie à l'aiguille a été proche de 100% en cas de biopsie positive mais seulement de 69.6% en cas de biopsie négative. L'analyse de l'ensemble de ces faits incite à adopter une attitude plus agressive c'est-à-dire à pratiquer des biopsies multiples au lieu d'une ponction unique pour réduire le taux des prélèvements ininterprétables et accroÎtre celui des résultats exacts.

     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

Assessment of the effects of exposure to extremely low-frequency magnetic fields on MDCK epithelial cell lines under a controlled environment

To assess the effects of exposure to extremely low-frequency magnetic fields (ELF-MFs) on MDCK cell lines, experiments were performed in a chamber under controlled conditions (temperature, humidity and CO₂). Therefore, the measured physicochemical and electrical changes in the cells are due solely to the magnetic field exposure and not to external factors. A developed sinusoidal magnetic field generator produced the ELF-MFs with a uniform magnetic field and adjustable intensity and frequency. Three experimental indicators were used: (i) transepithelial electrical impedance (TEEI); (ii) cell migration and proliferation; and (iii) expression of the proteins of the tight junctions, and changes in the area and shape of the cell nuclei. No significant effects on TEEI values were observed when 10 and 50 G 60 Hz magnetic fields were applied to confluent cell monolayers. There were no significant differences in migration and proliferation of the cell monolayer exposed to 60 Hz magnetic fields10 and 50 G , but a contact inhibition factor was observed. The expression of the CLDN-1 protein decreased by 90% compared with the control, while ZO-1 protein expression increased by 120%. No significant effects were observed in the area and shape of the cell nuclei. Experimentation in a controlled environment, under physiological conditions, ensures that the observed effects were strictly due to exposure to magnetic fields. Different exposure conditions are necessary to determine the impact on TEEI and cell migration–proliferation indicators.     

Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 treatment should be explored.