Presence of SARS-CoV-2 in urban effluents in south-east Buenos Aires, Argentina, May 2020 to March 2022.

Objectives: To implement and evaluate the use of wastewater sampling for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two coastal districts of Buenos Aires Province, Argentina. Methods: In General Pueyrredon district, 400 mL of wastewater samples were taken with an automatic sampler for 24 hours, while in Pinamar district, 20 L in total (2.2 L at 20-minute intervals) were taken. Samples were collected once a week. The samples were concentrated based on flocculation using polyaluminum chloride. RNA purification and target gene amplification and detection were performed using reverse transcription polymerase chain reaction for clinical diagnosis of human nasopharyngeal swabs. Results: In both districts, the presence of SARS-CoV-2 was detected in wastewater. In General Pueyrredon, SARS-CoV-2 was detected in epidemiological week 28, 2020, which was 20 days before the start of an increase in coronavirus virus disease 2019 (COVID-19) cases in the first wave (epidemiological week 31) and 9 weeks before the maximum number of laboratory-confirmed COVID-19 cases was recorded. In Pinamar district, the virus genome was detected in epidemiological week 51, 2020 but it was not possible to carry out the sampling again until epidemiological week 4, 2022, when viral circulation was again detected. Conclusions: It was possible to detect SARS-CoV-2 virus genome in wastewater, demonstrating the usefulness of the application of wastewater epidemiology for long-term SARS-CoV-2 detection and monitoring.

The impact of PKR activation: from neurodegeneration to cancer.

An inverse association between cancer and neurodegeneration is plausible because these biological processes share several genes and signaling pathways. Whereas uncontrolled cell proliferation and decreased apoptotic cell death governs cancer, excessive apoptosis contributes to neurodegeneration. Protein kinase R (PKR), an interferon-inducible double-stranded RNA protein kinase, is involved in both diseases. PKR activation blocks global protein synthesis through eIF2α phosphorylation, leading to cell death in response to a variety of cellular stresses. However, PKR also has the dual role of activating the nuclear factor κ-B pathway, promoting cell proliferation. Whereas PKR is recognized for its negative effects on neurodegenerative diseases, in part, inducing high level of apoptosis, the role of PKR activation in cancer remains controversial. In general, PKR is considered to have a tumor suppressor function, and some clinical data show a correlation between suppressed or inactivated PKR and a poor prognosis for several cancers. However, other studies show high PKR expression and activation levels in various cancers, suggesting that PKR might contribute to neoplastic progression. Understanding the cellular factors and signals involved in the regulation of PKR in these age-related diseases is relevant and may have important clinical implications. The present review highlights the current knowledge on the role of PKR in neurodegeneration and cancer, with special emphasis on its regulation and clinical implications.

Correction: Preoperative chemoradiotherapy for rectal cancer: the sensitizer role of the association between miR-375 and c-Myc.

[This corrects the article DOI: 10.18632/oncotarget.19393.].

Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery.

OBJECTIVE: To investigate the effect of parenteral administration of vitamin C on neutrophil apoptosis by determining Fas receptor expression and caspase-3, poly (ADP-ribose) polymerase (PARP), and Bcl-2 levels in neutrophils from septic abdominal surgery patients. STUDY DESIGN: Twenty septic abdominal surgery patients were studied in a prospective, randomized, double-blinded clinical trial. A group of healthy volunteers (n = 10) constituted a reference group for baseline parameter values. The patients were randomly assigned to a vitamin C-treated (n = 10) or placebo-treated (n = 10) group. For a 6-d period from 12 h post-surgery, the vitamin C group received 450 mg/d of the vitamin in 3 doses and the placebo group an identical administration of 5% dextrose. Early-morning peripheral blood samples were obtained daily from 24 h after vitamin C administration until d 6 post-surgery (T1d-T6d). RESULTS: Vitamin C group showed a nonsignificant reduction in Fas (CD95) expression on CD15-positive peripheral blood neutrophils, significantly decreased caspase-3, and PARP levels (caspase-3: T4d: P < 0.05, T5d: P < 0.05, T6d P < 0.01; and PARP: T3d: P < 0.05, T4d: P < 0.05, T6d: P < 0.05), and significantly increased Bcl-2 levels (T3d: P = 0.001) versus placebo group. CONCLUSIONS: Postoperative vitamin C treatment of septic abdominal surgery patients exerts an antiapoptotic effect on peripheral blood neutrophils, reducing caspase-3 and PARP levels, and increasing Bcl-2 levels. However, these antiapoptotic effects are not maintained at all time points.

Presence of SARS-CoV-2 in urban effluents in south-east Buenos Aires, Argentina, May 2020 to March 2022

[ABSTRACT]. Objectives. To implement and evaluate the use of wastewater sampling for detection of severe acute respira- tory syndrome coronavirus 2 (SARS-CoV-2) in two coastal districts of Buenos Aires Province, Argentina. Methods. In General Pueyrredon district, 400 mL of wastewater samples were taken with an automatic sam- pler for 24 hours, while in Pinamar district, 20 L in total (2.2 L at 20-minute intervals) were taken. Samples were collected once a week. The samples were concentrated based on flocculation using polyaluminum chloride. RNA purification and target gene amplification and detection were performed using reverse transcription poly- merase chain reaction for clinical diagnosis of human nasopharyngeal swabs. Results. In both districts, the presence of SARS-CoV-2 was detected in wastewater. In General Pueyrre- don, SARS-CoV-2 was detected in epidemiological week 28, 2020, which was 20 days before the start of an increase in coronavirus virus disease 2019 (COVID-19) cases in the first wave (epidemiological week 31) and 9 weeks before the maximum number of laboratory-confirmed COVID-19 cases was recorded. In Pinamar district, the virus genome was detected in epidemiological week 51, 2020 but it was not possible to carry out the sampling again until epidemiological week 4, 2022, when viral circulation was again detected. Conclusions. It was possible to detect SARS-CoV-2 virus genome in wastewater, demonstrating the useful- ness of the application of wastewater epidemiology for long-term SARS-CoV-2 detection and monitoring.

[RESUMEN]. Objetivos. Aplicar y evaluar la utilización de muestreos de aguas residuales como método para la detección del coronavirus del síndrome respiratorio agudo severo de tipo 2 (SARS-CoV-2) en dos distritos costeros de la Provincia de Buenos Aires, Argentina. Métodos. Se utilizó un dispositivo de muestreo automático para tomar muestras de 400 mL de las aguas residuales de 24 horas en el distrito de General Pueyrredon, mientras que en el distrito de Pinamar se tomaron muestras de 2,2 L a intervalos de 20 minutos hasta un volumen total de 20 L. Los muestreos se realizaron una vez por semana. Las muestras se concentraron mediante floculación con policloruro de aluminio. La purificación del ARN y la amplificación y detección del gen diana se llevaron a cabo mediante la prueba de reacción en cadena de la polimerasa con retrotranscripción para el diagnóstico clínico a partir de hisopados nasofaríngeos. Resultados. Se observó la presencia de SARS-CoV-2 en las aguas residuales de ambos distritos. En General Pueyrredon, el SARS-CoV-2 se halló en la semana epidemiológica 28 del 2020, es decir, 20 días antes del inicio del aumento de casos de enfermedad por coronavirus 2019 (COVID-19) registrado en la primera ola (semana epidemiológica 31) y nueve semanas antes de que se alcanzara el número máximo de casos de COVID-19 con confirmación de laboratorio. En el distrito de Pinamar se detectó el genoma viral en la semana epidemiológica 51 del 2020, pero solo se pudo volver a realizar el muestreo en la semana epidemiológica 4 del 2022, en la que se volvió a detectar la circulación del virus. Conclusiones. Se pudo detectar el genoma del virus SARS-CoV-2 en aguas residuales, lo que muestra la utilidad de la aplicación de la epidemiología de aguas residuales como método para la detección y el segui- miento del SARS-CoV-2 a largo plazo.

[RESUMO]. Objetivos. Implementar e avaliar o uso de amostragem de águas residuais na detecção do coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) em dois distritos costeiros da Província de Buenos Aires, Argentina. Métodos. No distrito de General Pueyrredon, amostras de 400 mL de águas residuais foram coletadas ao longo de 24 horas com um amostrador automático; já no distrito de Pinamar, foram coletados 20 L no total (2,2 L a intervalos de 20 minutos). As amostras foram coletadas uma vez por semana e concentradas por flocu- lação com cloreto de polialumínio. A purificação do RNA e a amplificação e detecção de genes-alvo foram realizadas por meio de reação em cadeia da polimerase com transcrição reversa para diagnóstico clínico de esfregaços nasofaríngeos humanos. Resultados. Detectou-se presença de SARS-CoV-2 em águas residuais dos dois distritos. Em General Puey- rredon, o SARS-CoV-2 foi detectado na semana epidemiológica 28 de 2020, ou seja, 20 dias antes do início de um aumento no número de casos da doença provocada pelo coronavírus de 2019 (COVID-19) na primeira onda (semana epidemiológica 31) e 9 semanas antes de se registrar o número máximo de casos de COVID-19 confirmados em laboratório. No distrito de Pinamar, o genoma viral foi detectado na semana epidemiológica 51 de 2020, mas não foi possível realizar a amostragem novamente até a semana epidemiológica 4 de 2022, quando a circulação do vírus foi novamente constatada. Conclusões. Foi possível detectar o genoma do vírus SARS-CoV-2 em águas residuais, demonstrando a uti- lidade da aplicação da epidemiologia baseada em águas residuais para detectar e monitorar o SARS-CoV-2 em longo prazo.

Presence of SARS-CoV-2 in urban effluents in south-east Buenos Aires, Argentina, May 2020 to March 2022 / Presencia del SARS-CoV-2 en aguas residuales urbanas del sudeste de Buenos Aires, Argentina, de mayo del 2020 a marzo del 2022 / Presença de SARS-CoV-2 em águas residuais urbanas no sudeste de Buenos Aires, Argentina, de maio de 2020 a março de 2022

ABSTRACT Objectives. To implement and evaluate the use of wastewater sampling for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two coastal districts of Buenos Aires Province, Argentina. Methods. In General Pueyrredon district, 400 mL of wastewater samples were taken with an automatic sampler for 24 hours, while in Pinamar district, 20 L in total (2.2 L at 20-minute intervals) were taken. Samples were collected once a week. The samples were concentrated based on flocculation using polyaluminum chloride. RNA purification and target gene amplification and detection were performed using reverse transcription polymerase chain reaction for clinical diagnosis of human nasopharyngeal swabs. Results. In both districts, the presence of SARS-CoV-2 was detected in wastewater. In General Pueyrredon, SARS-CoV-2 was detected in epidemiological week 28, 2020, which was 20 days before the start of an increase in coronavirus virus disease 2019 (COVID-19) cases in the first wave (epidemiological week 31) and 9 weeks before the maximum number of laboratory-confirmed COVID-19 cases was recorded. In Pinamar district, the virus genome was detected in epidemiological week 51, 2020 but it was not possible to carry out the sampling again until epidemiological week 4, 2022, when viral circulation was again detected. Conclusions. It was possible to detect SARS-CoV-2 virus genome in wastewater, demonstrating the usefulness of the application of wastewater epidemiology for long-term SARS-CoV-2 detection and monitoring.

RESUMEN Objetivos. Aplicar y evaluar la utilización de muestreos de aguas residuales como método para la detección del coronavirus del síndrome respiratorio agudo severo de tipo 2 (SARS-CoV-2) en dos distritos costeros de la Provincia de Buenos Aires, Argentina. Métodos. Se utilizó un dispositivo de muestreo automático para tomar muestras de 400 mL de las aguas residuales de 24 horas en el distrito de General Pueyrredon, mientras que en el distrito de Pinamar se tomaron muestras de 2,2 L a intervalos de 20 minutos hasta un volumen total de 20 L. Los muestreos se realizaron una vez por semana. Las muestras se concentraron mediante floculación con policloruro de aluminio. La purificación del ARN y la amplificación y detección del gen diana se llevaron a cabo mediante la prueba de reacción en cadena de la polimerasa con retrotranscripción para el diagnóstico clínico a partir de hisopados nasofaríngeos. Resultados. Se observó la presencia de SARS-CoV-2 en las aguas residuales de ambos distritos. En General Pueyrredon, el SARS-CoV-2 se halló en la semana epidemiológica 28 del 2020, es decir, 20 días antes del inicio del aumento de casos de enfermedad por coronavirus 2019 (COVID-19) registrado en la primera ola (semana epidemiológica 31) y nueve semanas antes de que se alcanzara el número máximo de casos de COVID-19 con confirmación de laboratorio. En el distrito de Pinamar se detectó el genoma viral en la semana epidemiológica 51 del 2020, pero solo se pudo volver a realizar el muestreo en la semana epidemiológica 4 del 2022, en la que se volvió a detectar la circulación del virus. Conclusiones. Se pudo detectar el genoma del virus SARS-CoV-2 en aguas residuales, lo que muestra la utilidad de la aplicación de la epidemiología de aguas residuales como método para la detección y el seguimiento del SARS-CoV-2 a largo plazo.

RESUMO Objetivos. Implementar e avaliar o uso de amostragem de águas residuais na detecção do coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) em dois distritos costeiros da Província de Buenos Aires, Argentina. Métodos. No distrito de General Pueyrredon, amostras de 400 mL de águas residuais foram coletadas ao longo de 24 horas com um amostrador automático; já no distrito de Pinamar, foram coletados 20 L no total (2,2 L a intervalos de 20 minutos). As amostras foram coletadas uma vez por semana e concentradas por floculação com cloreto de polialumínio. A purificação do RNA e a amplificação e detecção de genes-alvo foram realizadas por meio de reação em cadeia da polimerase com transcrição reversa para diagnóstico clínico de esfregaços nasofaríngeos humanos. Resultados. Detectou-se presença de SARS-CoV-2 em águas residuais dos dois distritos. Em General Pueyrredon, o SARS-CoV-2 foi detectado na semana epidemiológica 28 de 2020, ou seja, 20 dias antes do início de um aumento no número de casos da doença provocada pelo coronavírus de 2019 (COVID-19) na primeira onda (semana epidemiológica 31) e 9 semanas antes de se registrar o número máximo de casos de COVID-19 confirmados em laboratório. No distrito de Pinamar, o genoma viral foi detectado na semana epidemiológica 51 de 2020, mas não foi possível realizar a amostragem novamente até a semana epidemiológica 4 de 2022, quando a circulação do vírus foi novamente constatada. Conclusões. Foi possível detectar o genoma do vírus SARS-CoV-2 em águas residuais, demonstrando a utilidade da aplicação da epidemiologia baseada em águas residuais para detectar e monitorar o SARS-CoV-2 em longo prazo.

Preoperative chemoradiotherapy for rectal cancer: the sensitizer role of the association between miR-375 and c-Myc.

Administration of chemoradiation before tumor resection has revolutionized the management of locally advanced rectal cancer, but many patients have proven resistant to this preoperative therapy. Our group recently reported a negative correlation between c-Myc gene expression and this resistance. In the present study, integrated analysis of miRNA and mRNA expression profiles was conducted in 45 pre-treatment rectal tumors in order to analyze the expressions of miRNAs and c-Myc and their relationship with clinicopathological factors and patient survival. Twelve miRNAs were found to be differentially expressed by responders and non-responders to the chemoradiation. Functional classification revealed an association between the differentially expressed miRNAs and c-Myc. Quantitative real-time PCR results showed that miRNA-148 and miRNA-375 levels were both significantly lower in responders than in non-responders. Notably, a significant negative correlation was found between miRNA-375 expression and c-Myc expression. According to these findings, miRNA-375 and its targeted c-Myc may be useful as a predictive biomarker of the response to neoadjuvant treatment in patients with locally advanced rectal cancer.

Expression profiling of rectal tumors defines response to neoadjuvant treatment related genes.

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.