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Wastewater treatment plants (WWTPs) are the final stage of the anthropogenic water cycle where a wide range of chemical and biological markers of human activity can be found. In COVID-19 disease contexts, wastewater surveillance has been used to infer community trends based on viral abundance and SARS-CoV-2 RNA variant composition, which has served to anticipate and establish appropriate protocols to prevent potential viral outbreaks. Numerous studies worldwide have provided reliable and robust tools to detect and quantify SARS-CoV-2 RNA in wastewater, although due to the high dilution and degradation rate of the viral RNA in such samples, the detection limit of the pathogen has been a bottleneck for the proposed protocols so far. The current work provides a comprehensive and systematic study of the different parameters that may affect the detection of SARS-CoV-2 RNA in wastewater and hinder its quantification. The results obtained using synthetic viral RNA as a template allow us to consider that 10 genome copies per µL is the minimum RNA concentration that provides reliable and consistent values for the quantification of SARS-CoV-2 RNA. RT-qPCR analysis of wastewater samples collected at the WWTP in Salamanca (western Spain) and at six pumping stations in the city showed that below this threshold, positive results must be confirmed by sequencing to identify the specific viral sequence. This allowed us to find correlations between the SARS-CoV-2 RNA levels found in wastewater and the COVID-19 clinical data reported by health authorities. The close match between environmental and clinical data from the Salamanca case study has been confirmed by similar experimental approaches in four other cities in the same region. The present methodological approach reinforces the usefulness of wastewater-based epidemiology (WBE) studies in the face of future pandemic outbreaks.

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Background: Colon cancer in elderly patients is an increasing problem due to its prevalence and progressive aging population. Prehabilitation has experienced a great grown in this field. Whether it is the best standard of care for these patients has not been elucidated yet. Methods: A retrospective comparative cohort study of three different standards of care for elderly colon cancer patients (>65 years) was conducted. A four-weeks trimodal prehabilitation program (PP), enhanced recovery program (ERP) and conventional care (CC) were compared. Global complications, major complications (Clavien-Dindo ≥ 3), reinterventions, mortality, readmission and length of stay were measured. Optimal recovery, defined as postoperative course without major complications, no mortality, hospital discharge before the fifth postoperative day and without readmission, was the primary outcome measure. The influence of standard of care in optimal recovery and postoperative outcomes was assessed with univariate and multivariate logistic regression models. Results: A total of 153 patients were included, 51 in each group. Mean age was 77.9 years. ASA Score distribution was different between groups (ASA III-IV: CC 56.9%, ERP 25.5%, PP 58.9%; p = 0.014). Optimal recovery rate was 55.6% (PP 54.9%, ERP 66.7%, CC 45.1%; p = 0.09). No differences were found in major complications (p = 0.2) nor reinterventions (p = 0.7). Uneventful recovery favors ERP and PP groups (p = 0.046 and p = 0.049 respectively). Conclusions: PP and ERP are safe and effective for older colon cancer patients. Fewer overall complications and readmissions happened in ERP and PP patients. Major complications were independent of the standard of care used. (AU)

Introducción: El cáncer de colon (CC) en pacientes de edad avanzada es un problema creciente por su prevalencia y envejecimiento progresivo de la población. La prehabilitación ha experimentado un gran crecimiento en este campo sin haberse dilucidado si es el mejor estándar de cuidados para estos pacientes. Métodos: Estudio retrospectivo comparativo de cohortes de tres estándares diferentes de cuidados para pacientes mayores de 65 años con CC. Se compararon un programa de prehabilitación (PP) trimodal de cuatro semanas, uno de recuperación intensificada (RI) y cuidados convencionales (CC). Se midieron complicaciones globales, complicaciones mayores (Clavien-Dindo ≥ 3), reintervenciones, mortalidad, reingresos y estancia hospitalaria. La recuperación óptima fue la medida de resultado primaria. La influencia del estándar de atención en la recuperación óptima y los resultados postoperatorios se evaluó con modelos de regresión logística univariante y multivariante. Resultados: Se incluyeron 153 pacientes, 51 por grupo. La edad media fue 77,9 años. La distribución del ASA fue diferente entre los grupos (ASA III–IV: CC 56,9%, RI 25,5%, PP 58,9%; p = 0,014). La tasa de recuperación óptima fue del 55,6% (PP 54,9%, RI 66,7%, CC 45,1%; p = 0,09). No se encontraron diferencias en complicaciones mayores (p = 0,2) ni reintervenciones (p = 0,7). La recuperación sin incidencias favorece a los grupos RI y PP (p = 0,046 y p = 0,049 respectivamente). Conclusiones: PP y RI son seguros y efectivos para pacientes mayores con CC. Las complicaciones generales y reingresos en pacientes con RI y PP fueron menores. Las complicaciones mayores resultaron independientes del estándar de cuidados utilizado. (AU)

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The transcription factor THCTF1 from Trichoderma harzianum, previously linked to the production of 6-pentyl-2H-pyran-2-one (6-PP) derivatives and antifungal activity against Fusarium oxysporum, has been related in this study to conidiation, production of an array of volatile organic compounds (VOCs) and expression of methyltransferase genes. VOCs emitted by three T. harzianum strains (wild type T34, transformant ΔD1-38 that is disrupted in the Thctf1 gene encoding the transcription factor THCTF1, and ectopic integration transformant ΔJ3-16) were characterized by Proton Transfer Reaction-Quadrupole interface-Time-Of-Flight-Mass Spectrometry (PTR-Qi-TOF-MS). Thctf1 disruption affected the production of numerous VOCs such as the antifungal volatiles 2-pentyl furan and benzaldehyde which were under-emitted, and acetoine, a plant systemic defense inductor, which was over-emitted. Biological assays show that VOCs regulated by THCTF1 are involved in the T. harzianum antifungal activity against Botrytis cinerea and in the beneficial effects leading to Arabidopsis plant development. The VOC blend from the disruptant ΔD1-38: (i) inhibited Arabidopsis seed germination for at least 26 days and (ii) when applied to Arabidopsis seedlings resulted in increased jasmonic acid- and salicylic acid-dependent defenses.

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BACKGROUND: Colon cancer in elderly patients is an increasing problem due to its prevalence and progressive aging population. Prehabilitation has experienced a great grown in this field. Whether it is the best standard of care for these patients has not been elucidated yet. METHODS: A retrospective comparative cohort study of three different standards of care for elderly colon cancer patients (>65 years) was conducted. A four-weeks trimodal prehabilitation program (PP), enhanced recovery program (ERP) and conventional care (CC) were compared. Global complications, major complications (Clavien-Dindo ≥ 3), reinterventions, mortality, readmission and length of stay were measured. Optimal recovery, defined as postoperative course without major complications, no mortality, hospital discharge before the fifth postoperative day and without readmission, was the primary outcome measure. The influence of standard of care in optimal recovery and postoperative outcomes was assessed with univariate and multivariate logistic regression models. RESULTS: A total of 153 patients were included, 51 in each group. Mean age was 77.9 years. ASA Score distribution was different between groups (ASA III-IV: CC 56.9%, ERP 25.5%, PP 58.9%; p = 0.014). Optimal recovery rate was 55.6% (PP 54.9%, ERP 66.7%, CC 45.1%; p = 0.09). No differences were found in major complications (p = 0.2) nor reinterventions (p = 0.7). Uneventful recovery favors ERP and PP groups (p = 0.046 and p = 0.049 respectively). CONCLUSIONS: PP and ERP are safe and effective for older colon cancer patients. Fewer overall complications and readmissions happened in ERP and PP patients. Major complications were independent of the standard of care used.

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BACKGROUND: The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC. METHODS: The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology. RESULTS: Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67. CONCLUSIONS: Single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.

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BACKGROUND: The main risk factors for head and neck cancer (HNC) are tobacco and alcohol use. However, an important fraction of oropharyngeal cancer (OPC) is caused by human papillomaviruses (HPV), a subgroup with increasing incidence in several western countries. METHODS: As part of the HPV-AHEAD study, we assessed the role of HPV infection in 772 archived tissue specimens of Belgian HNC patients: 455 laryngeal (LC), 106 oral cavity (OCC), 99 OPC, 76 hypopharyngeal (HC), and 36 unspecified parts of the head and neck. All specimens were tested for HPV DNA (21 genotypes); whereof all HPV DNA-positives, all HPV DNA-negative OPCs and a random subset of HPV DNA-negatives of the other HNC-sites were tested for the presence of type-specific HPV RNA and p16INK4a over-expression. RESULTS: The highest HPV DNA prevalence was observed in OPC (36.4 %), and was significantly lower (p < 0.001) in the other HNCs (OCC:7.5 %, LC:6.6 %). HPV16 was the most common HPV-genotype in all HNCs. Approximately 83.0 % of the HPV DNA-positive OPCs tested HPV RNA or p16-positive, compared to about 37.5 % and 44.0 % in OCC and LC, respectively. Estimation of the attributable fraction of an HPV infection in HNC was very similar for HPV RNA or p16 in addition to DNA-positivity; with 30 % for OPC, and 3 % for OCC and LC. CONCLUSION: Our study confirms the heterogeneity of HPV DNA prevalence across anatomical sites in HNC, with a predominance of HPV16 in all sites. The estimated proportion of HPV-driven HNC in Belgium, during the period 1980-2014, was 10 times higher in OPC compared to OCC and LC.

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This study examined the microbicidal activity of ultraviolet (UV)-C185-256-nm irradiance (robot 1) and ozone generated at UV-C185-nm by low-pressure mercury vapor lamps (robot 2) adapted to mobile robotic devices for surface decontamination, which was achieved in less than 1 h. Depending on their wall structure and outer envelopes, many microorganisms display different levels of resistance to decontaminating agents. Thus, the need for novel disinfection approaches is further exacerbated by the increased prevalence of multidrug-resistant bacteria, as well as the potential of novel microorganisms, with the ability to cause disease outbreaks. To set up a rapid and effective approach for microorganisms propagation prevention, we focused on the effects of UV-C and ozone on a distinct microorganism survival ratio. A set of microorganisms, including Escherichia coli, Micrococcus luteus, Saccharomyces cerevisiae, Trichoderma harzianum, and Bacillus subtilis, were used to evaluate the disinfection power of UV-C and UV-C plus ozone generating robots. UV-C disinfection can be suited to ad hoc tasks, is easy to operate, requires low maintenance, does not have the need for the storage of dangerous chemicals, and does not produce by-products that may affect human health and the environment. The robotic cumulative irradiation technology developed (fluence accumulated values of 2.28 and 3.62 mJ cm-2, for robot 1 and 2, respectively), together with the production of ozone (with a maximum peak of 0.43 ppm) capable of reaching UV-C shaded surfaces, and analyzed in the current study, despite being designed for the need to reduce the risk of epidemic outbreaks in real-life scenarios, represents a versatile tool that could be employed for air and surface disinfection within many circumstances that are faced daily.

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Root-knot nematodes (RKN) are major crop pathogens worldwide. Trichoderma genus fungi are recognized biocontrol agents and a direct activity of Trichoderma atroviride (Ta) against the RKN Meloidogyne javanica (Mj), in terms of 42% reduction of number of galls (NG), 60% of number of egg masses and 90% of number of adult nematodes inside the roots, has been observed in tomato grown under greenhouse conditions. An in vivo split-root designed experiment served to demonstrate that Ta induces systemic resistance towards Mj, without the need for the organisms to be in direct contact, and significantly reduces NG (20%) and adult nematodes inside tomato roots (87%). The first generation (F1) of Ta-primed tomato plants inherited resistance to RKN; although, the induction of defenses occurred through different mechanisms, and in varying degrees, depending on the Ta-Mj interaction. Plant growth promotion induced by Ta was inherited without compromising the level of resistance to Mj, as the progeny of Ta-primed plants displayed increased size and resistance to Mj without fitness costs. Gene expression results from the defense inductions in the offspring of Ta-primed plants, suggested that an auxin-induced reactive oxygen species production promoted by Ta may act as a major defense strategy during plant growth.

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The synthesis and characterization of 3'-fluoromethotrexate (FMTX), a novel fluorine-labeled analogue of methotrexate, are presented. Molecular modeling studies indicate that the fluorine atom causes only minimal changes in the structure/binding in the complex of the antifolate with thymidine synthetase and dihydrofolate reductase (DHFR). The in vitro cytotoxicity of this compound is shown to be equivalent to that of the parent antifolate compound. While the focus of this report is the synthetic technique of FMTX, it is also demonstrated that tumor accumulation of the labeled compound in vivo can be observed via 19F magnetic resonance spectroscopy (MRS) in a human tumor xenograft model.

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