Mortality Rate and Acute Kidney Injury Prevalence Reduction in COVID-19 Critical Patients Treated with Hemoperfusion.

Introduction: Coronavirus disease 2019 (COVID-19) induces organic damage mainly through the patient's immune overreaction. Hemoperfusion (HPF) can remove inflammatory cytokines and can reduce the negative effects of cytokine storm in COVID-19. We compared the mortality rate, inflammatory response, and acute kidney injury (AKI) prevalence among patients suffering from respiratory insufficiency secondary to COVID-19 treated with and without HPF with HA330 cartridge. Methods: Mortality rate, serum creatinine, and ferritin values were compared between patients suffering from respiratory insufficiency secondary to COVID-19 who received conventional treatment and another group of patients who additionally received four sessions of HPF with HA330. Results: Of 116 patients suffering from acute respiratory insufficiency secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one group (n: 84) received support treatment and the other group (n: 32) additionally received HPF with HA330 cartridge. Both groups had no renal disease and similar age and comorbidities at admission, except for obesity and mechanical ventilation requirement, which were significantly higher in the HPF group. Mortality rate (61% vs. 31%, P: 0.008), serum creatinine (1.4 vs. 0.5 mg/dl, P < 0.001), and post-HPF serum ferritin (2868 vs. 1675, P < 0.001) were significantly lower in the HPF group. Conclusion: Mortality rate, serum ferritin, and AKI were significantly reduced in critical COVID-19 patients who received HPF with HA330 cartridge than in those who did not receive it. These results were obtained despite the HPF group risk factors, such as obesity and mechanical ventilation, worsening its prognosis.

Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer.

BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

B-Box transcription factor BBX28 requires CONSTITUTIVE PHOTOMORPHOGENESIS1 to induce shade-avoidance response in Arabidopsis thaliana.

Shade avoidance syndrome is an important adaptive strategy. Under shade, major transcriptional rearrangements underlie the reallocation of resources to elongate vegetative structures and redefine the plant architecture to compete for photosynthesis. BBX28 is a B-box transcription factor involved in seedling de-etiolation and flowering in Arabidopsis (Arabidopsis thaliana), but its function in shade-avoidance response is completely unknown. Here, we studied the function of BBX28 using two mutant and two transgenic lines of Arabidopsis exposed to white light and simulated shade conditions. We found that BBX28 promotes hypocotyl growth under shade through the phytochrome system by perceiving the reduction of red photons but not the reduction of photosynthetically active radiation or blue photons. We demonstrated that hypocotyl growth under shade is sustained by the protein accumulation of BBX28 in the nuclei in a CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1)-dependent manner at the end of the photoperiod. BBX28 up-regulates the expression of transcription factor- and auxin-related genes, thereby promoting hypocotyl growth under prolonged shade. Overall, our results suggest the role of BBX28 in COP1 signaling to sustain the shade-avoidance response and extend the well-known participation of other members of BBX transcription factors for fine-tuning plant growth under shade.

Biocontrol of L. monocytogenes with Selected Autochthonous Lactic Acid Bacteria in Raw Milk Soft-Ripened Cheese under Different Water Activity Conditions.

The effect of selected autochthonous Lactic Acid Bacteria (LAB) against Listeria monocytogenes was evaluated in two elaborations of soft-ripened cheese performed under high and low relative humidity (RH) elaborations, to achieve aw ranging from 0.97 to 0.94 in ripened cheeses. Two selected autochthonous strains of Lacticaseibacillus casei 31 and 116 were used. In each elaboration, 8 batches were physicochemically and microbiologically evaluated throughout the ripening process. The aw and pH decreased during ripening to final values ranging from 0.944 to 0.972 aw and 5.0 to 5.3 pH, respectively. LAB was the only microbial group that increased throughout the ripening in high and low RH elaborations. In batches that were uninoculated with LAB strains, L. monocytogenes was either maintained at the initial inoculation level or showed a slight reduction by the end of the ripening process. However, in LAB-inoculated batches in the two elaborations, steady decreases of L. monocytogenes were observed throughout maturation. L. casei 31 alone or in combination with strain 116 provoked reductions of 2 to 4 log CFU/g in L. monocytogenes over 60 days of ripening, which could be enough as a strategy for biocontrol to deal with the usual contamination by L. monocytogenes during cheese processing.

Prevalence of Listeria monocytogenes in RTE Meat Products of Quevedo (Ecuador).

Listeria monocytogenes is a foodborne pathogen that causes listeriosis and can be a problem in areas where meat products are sold at unregulated storage temperatures. In this work, the prevalence of L. monocytogenes was determined in the five most widely traded meat products in the province of Quevedo (Ecuador): bacon, "chorizo paisa", grilled hamburger meat, mortadella, and salami. A total of 1000 samples of these products were analyzed in two seasons of the year (dry season/rainy season). All L. monocytogenes isolates were confirmed by PCR with primers designed for the iap gene. Furthermore, the positive samples were quantified for L. monocytogenes. Of the 1000 meat products analyzed, 163 were positive for L. monocytogenes (16.3%). The prevalence of L. monocytogenes in the two seasons in different meat products was as follows: 22.5% in mortadella, 19% in hamburger meat, 15% in bacon, 14.5% in chorizo paisa and 10.5% in salami. In addition, the concentration of L. monocytogenes in most of the positive samples was in the range of 4-6 log CFU/g or even higher. The results show the need for improvements in the hygienic measures and meat storage temperatures in Quevedo (Ecuador) to avoid risks of foodborne listeriosis.

Antilisterial activity of cinnamon essential oil, pomegranate extract, or strawberry tree extract against Listeria monocytogenes in slices of dry-cured ham and pork loin.

Owing to concerns about the antimicrobial resistance of agents that can prevent the growth of Listeria monocytogenes in meat, researchers have investigated natural preservatives with antilisterial effects. However, in vivo application of essential oils and plant extracts usually results in reduced antimicrobial activity in meat products when compared to in vitro studies. This study aimed to evaluate the in vivo antimicrobial activity of cinnamon essential oil, pomegranate, and strawberry tree extracts in slices of dry-cured ham and pork loin against L. monocytogenes. Fragments of sterile dry-cured ham were inoculated with 100 µL cinnamon oil 0.5%, pomegranate, or strawberry crude extract. After 10 min, 100 µL of L. monocytogenes serotype 4b (104 colony-forming unit [CFU]/mL) was inoculated, and samples were incubated at 7 °C for 7 d to simulate the processing and storage temperature conditions of dry-cured meat products. L. monocytogenes was detected and quantified. Only strawberry extract presented significant differences (P < 0.05) from the control; thus, it was selected for the assay with 2% and 4% salt-treated pork loin. The strawberry tree extract significantly (P < 0.05) reduced the growth of L. monocytogenes in dry-cured ham. However, it could not reduce L. monocytogenes growth in pork loin, regardless of the salt concentration. This is the first report on the antimicrobial effect of strawberry tree leaf extract against L. monocytogenes in dry-cured ham.

Effect of acidic conditions on the growth and expression of two virulence genes of Listeria monocytogenes serotype 4b.

In this work, the effect of the usual acidic conditions of dry-cured fermented foods (pH values between 4.5 and 6), on the growth and expression of the virulence genes, hly and inlA, of Listeria monocytogenes serotype 4b, was evaluated. To analyse the expression of the inlA gene, a novel real-time PCR (qPCR) method using SYBR® Green methodology was developed. L. monocytogenes levels increased as the pH did and they were kept constant throughout incubation time at pH 4.5. However, a significant increase in the relative expression of the virulence genes was detected in most of the acidic conditions in all the incubation times. The most pronounced upregulation of the relative expression of the virulence genes was found at pH 4.5. The efficient inlA-based qPCR method could be of interest to check changes in the expression of such virulence gene of this pathogenic bacterium in acidic environments.

Effect of a Selected Protective Culture of Lactilactobacillus sakei on the Evolution of Volatile Compounds and on the Final Sensorial Characteristics of Traditional Dry-Cured Fermented "Salchichón".

BACKGROUND: In this work, the effect of a selected starter culture of Lactilactobacillus sakei 205 on the evolution of volatile compounds throughout the ripening process and on the final sensorial characteristics of traditional dry-cured fermented "salchichón" was evaluated. METHODS: "Salchichón" sausages were prepared, inoculated with L. sakei 205, and ripened for 90 days. Volatile compounds were analyzed throughout the ripening by GC-MS. In the final product, instrumental texture and color were determined. In addition, sensorial analysis was performed by a semi-trained panel. RESULTS: The inoculation of L. sakei 205 does not influence the texture and color parameters of ripened "salchichón". However, an increase in volatile compounds derived from amino acid catabolism and microbial esterification and a decrease in compounds derived from lipid oxidation, mainly hexanal, were observed throughout the ripening time as a consequence of L. sakei inoculation, which could have a positive effect on the flavor development of the dry-cured fermented "salchichón". CONCLUSIONS: The use of selected strains of lactic acid bacteria (LAB) such as L. sakei 205 as a protective culture could be recommended to improve the quality of traditional "salchichón".

Evolution of Volatile Compounds during Ripening and Final Sensory Changes of Traditional Raw Ewe's Milk Cheese "Torta del Casar" Maturated with Selected Protective Lactic Acid Bacteria.

In traditional soft ripened cheeses made with raw milk, the use of protective cultures is infrequent. In the present work, the effect of selected (for their activity against Listeria monocytogenes) protective cultures of Lactocaseibacillus casei 116 and Lactococcus garvieae 151 was evaluated, on the evolution of volatile compounds throughout the ripening and on the final sensory characteristics of traditional soft ripened "Torta del Casar" cheese. For this, both strains were separately inoculated in raw cheeses and ripened for 90 days. The selected LAB strains did not affect physicochemical parameters, including texture and color of the ripened cheeses. However, they could have a positive effect on the aroma, for the generation of methyl branched acids and for the reduction in compounds derived from ß-oxidation of fatty acids. Thus, these protective cultures, in addition to contributing to their safety, could improve quality of the ripened cheeses.

Seroprevalence and immunological memory against SARS-CoV-2 in lung cancer patients: the SOLID study.

BACKGROUND: At present, we did not find any articles that studied seroprevalence and its persistence several months later in lung cancer patients in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most patients with coronavirus disease 2019 (COVID-19) go on to develop antibodies (Abs) against viral proteins. However, it is not known how long these Abs last nor whether cancer treatments could affect the duration of immune response. METHODS: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 infection was carried out in 50 Spanish hospitals. Eligibility criterion was the diagnosis of any lung cancer. The determination of anti-SARS-CoV-2 IgG Abs was performed by qualitative immuno-enzymatic assay using enzyme-linked immunosorbent assay (ELISA) kit from NovaLisa whose Abs target the recombinant antigen N of the nucleocapsid of SARS-CoV-2. The first Ab determination was performed between April 21 and June 3, 2020. The second Ab determination was performed in all previously seropositive patients, between September 10 and November 20, 2020. Study objectives were to prospectively determine seroprevalence in unselected lung cancer patients during the first wave of the pandemic; the persistence of immunity; protection or lack thereof against reinfection; and the influence of treatments on maintenance or loss of immunity. RESULTS: Of 1,500 patients, 128 were seropositive, overall prevalence of 8.5% seropositivity [95% confidence interval (CI): 7.2-10.1%]. Seventy-five percent were in active cancer treatment. Forty-seven point seven percent of IgG positive participants had experienced a symptomatic illness suspected of being infected with SARS-CoV-2 (95% CI: 38.8-56.6%). A second determination was performed on average 4.5 months later [interquartile range (IQR), 4.0-5.0 months] and obtained for 104 of the initially seropositive patients (81%), it could not be obtained in 24 patients, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% of patients. The severity of the infection, the need for hospitalization (P=0.032) and the presence of symptoms at diagnosis (P=0.02) were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Abs loss. CONCLUSIONS: Immunity against SARS-CoV-2 does not appear to be compromised by treatment and persists beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04407143.

Strategies for Biocontrol of Listeria monocytogenes Using Lactic Acid Bacteria and Their Metabolites in Ready-to-Eat Meat- and Dairy-Ripened Products.

Listeria monocytogenes is one of the most important foodborne pathogens. This microorganism is a serious concern in the ready-to-eat (RTE) meat and dairy-ripened products industries. The use of lactic acid bacteria (LAB)-producing anti-L. monocytogenes peptides (bacteriocins) and/or lactic acid and/or other antimicrobial system could be a promising tool to control this pathogen in RTE meat and dairy products. This review provides an up to date about the strategies of use of LAB and their metabolites in RTE meat products and dairy foods by selecting the most appropriate strains, by analysing the mechanism by which they inhibit L. monocytogenes and methods of effective application of LAB, and their metabolites in these kinds of products to control this pathogen throughout the processing and storage. The selection of LAB with anti-L. monocytogenes activity allows to dispose of effective strains in meat and dairy-ripened products, achieving reductions form 2-5 logarithmic cycles of this pathogen throughout the ripening process. The combination of selected LAB strains with antimicrobial compounds, such as acid/sodium lactate and other strategies, as the active packaging could be the next future innovation for eliminating risk of L. monocytogenes in meat and dairy-ripened products.

Antimicrobial activity of essential oils and natural plant extracts against Listeria monocytogenes in a dry-cured ham-based model.

BACKGROUND: Listeria monocytogenes is a widespread common contaminant in food production facilities during preparation, storage, and distribution, and minimally processed ready-to-eat products are considered at high risk of contamination by this bacterium. Increased antibiotic resistance has led researchers to search for plant-based natural alternatives to control pathogenic microorganisms. Among these products, essential oils and plant extracts have previously shown antimicrobial activity and are possible alternatives to manage food pathogens. In this study, commercial essential oils (cinnamon, clove, oregano, ginger, and thyme) and plant extracts (pomegranate, acorn, olive, strawberry tree, and dog rose) were tested against L. monocytogenes in a dry-cured ham-based model. RESULTS: Essential oils and plant extracts were screened by agar diffusion and minimum inhibitory concentration for anti-L. monocytogenes activity. Cinnamon, pomegranate, and strawberry trees returned the strongest results and were therefore evaluated in a dry-cured ham-based medium assay with water activity of 0.93 or 0.95. The 10% essential oil of cinnamon was capable of completely inhibiting bacterial growth, while strawberry tree and pomegranate extract also showed antilisterial activity (P > 0.05). Water activity influenced the bacterial count of L. monocytogenes in a dry-cured ham-based medium. CONCLUSIONS: There was a reduction in L. monocytogenes with the application of cinnamon essential oil but, because of the negative sensory impact of this particular compound in meat products, we suggest the use of pomegranate or strawberry tree for the biocontrol of Listeria in ready-to-eat products. © 2021 Society of Chemical Industry.

Control of Listeria monocytogenes growth and virulence in a traditional soft cheese model system based on lactic acid bacteria and a whey protein hydrolysate with antimicrobial activity.

"Torta del Casar" is a Spanish soft-ripened cheese made with sheep's raw milk and subjected to a short ripening process, which favors the growth of pathogenic microorganisms including Listeria monocytogenes. The development of strategies to control pathogens and minimize health risks associated with the presence of L. monocytogenes in these products is of great interest. In this regard, the anti-Listeria activity of a whey protein hydrolysate (ProH) alone or combined with six lactic acid bacteria strains isolated from cheese was evaluated in this study as a biocontrol strategy using a "Torta del Casar" cheese-based medium. The most active combinations of lactic acid bacteria assayed induced a reduction higher than two logarithmic units in the growth of L. monocytogenes (serotype 4b) compared to their respective control when they were co-inoculated in "Torta del Casar" cheese-based medium at 7 °C for 7 days. In addition, the observed downregulation of some key virulence genes of L. monocytogenes suggests that the strain Lactiplantibacillus plantarum B2 alone and combined with the strain Lactiplantibacillus spp. B4 are good candidates to be used as biocontrol agents against L. monocytogenes growth in traditional soft cheeses based on raw milk during their storage at refrigeration temperatures.

Growth and Expression of Virulence Genes of Listeria monocytogenes during the Processing of Dry-Cured Fermented "Salchichón" Manufactured with a Selected Lactilactobacillus sakei.

The effect of the dry-cured fermented processing of "salchichón" inoculated with a selected strain of Lactilactobacillus sakei (205) on the growth and transcriptional response of three virulence genes (plcA, hly, and iap) of Listeria monocytogenes was evaluated. For this, three different batches of "salchichón" were analyzed: batch B (inoculated only with L. sakei), batch L (inoculated only with L. monocytogenes), and batch L + B (inoculated with both microorganisms). Sausages were ripened for 90 days according to a traditional industrial process. The processing of "salchichón" provoked a reduction in L. monocytogenes counts of around 2 log CFU/g. The downregulation of the expression of the three genes was found at the end of ripening when the water activity (aw) of "salchichón" was <0.85 aw. The combined effect on the reduction in L. monocytogenes counts together with the downregulation in the expression of the virulence genes throughout the "salchichón" processing could be of great interest to control the hazard caused by the presence of this pathogenic bacterium.

Effect of the Dry-Cured Fermented Sausage "Salchichón" Processing with a Selected Lactobacillus sakei in Listeria monocytogenes and Microbial Population.

In the present work, the effect of processing of dry-cured fermented sausage "salchichón" spiked with the selected Lactobacillus sakei 205 was challenge-tested with low and high levels of L. monocytogenes. The evolution of the natural microbial population throughout the "salchichón" ripening was also evaluated. For this, a total of 150 "salchichón" were elaborated and divided into six equal cases which were inoculated with different levels of L. monocytogenes, and L. sakei 205. Afterwards, sausages were ripened for 90 days according to a typical industrial process. Moisture content (%) and water activity (aw) decreased throughout the ripening up to values around 26% and 0.78, respectively. No differences for moisture content, aw, pH, NaCl and nitrite concentration were observed between the analyzed cases. Lactic acid bacteria counts in the L. sakei 205 inoculated cases were always higher than 6 log CFU g-1 during ripening. Enterobacteriaceae counts were reduced during ripening until non-detectable levels at the end of processing. Reductions in L. monocytogenes counts ranged from 1.6 to 2.2 log CFU g-1; therefore, the processing of "salchichón" itself did not allow the growth of this pathogen. Reduction in L. monocytogenes was significantly higher in the cases inoculated with L. sakei 205.

Mucosectomía endoscópica para cáncer gástrico temprano: una alternativa vigente / Endoscopic mucosal resection for early gastric cancer: A current alternative

Resumen La mucosectomía endoscópica ha probado ser una alternativa efectiva para el tratamiento del cáncer gástrico temprano; sin embargo, se requiere de un seguimiento estricto para asegurar una conducta de manejo adecuada en caso de recurrencia. Se presenta el caso de un paciente de 54 años, con hallazgo incidental de un carcinoma gástrico temprano, a quien se le realizó mucosectomía endoscópica, con un reporte final de histopatología compatible con adenocarcinoma gástrico temprano y márgenes de resección negativos, con un seguimiento endoscópico e histopatológico a 2 meses negativos para malignidad.

Abstract Endoscopic mucosal resection has proven to be an effective alternative for the treatment of early gastric cancer. However, strict follow-up is necessary to ensure adequate management in the event of recurrence. This is the case of a 54-year-old patient with an incidental finding of early gastric carcinoma. He underwent endoscopic mucosal resection, with a final histopathology report compatible with early gastric adenocarcinoma and negative resection margins. Endoscopic and histopathological follow-up at 2 months showed negative results for malignancy.

Impact of Water Activity on the Inactivation and Gene Expression of Listeria monocytogenes during Refrigerated Storage of Pressurized Dry-Cured Ham.

Listeria monocytogenes population and the expression patterns of three virulence (plcA, hly, and iap) and one stress-related (sigB) genes in dry-cured ham with different water activity (aw) values (0.92, 0.88, and 0.84) and treated with high pressure processing (HPP, 450 MPa/10 min and 600 MPa/5 min) were monitored throughout 30 days (d) at 4 °C. The antimicrobial effect of HPP at 600 MPa against L. monocytogenes S4-2 (serotype 1/2b) and S12-1 (serotype 1/2c) was greater in dry-cured ham with aw values of 0.92, with reductions of 2.5 and 2.8 log units, respectively. The efficacy of HPP treatments decreased at lower aw values. Regarding gene expression, L. monocytogenes strains responded differently to HPP. For strain S4-2, the four target genes were generally overexpressed in dry-cured ham immediately after HPP treatments at the three aw values investigated, although the extent of this induction was lower in the samples pressurized at 600 MPa and with aw values of 0.84. For strain S12-1, the expression of all target genes was repressed at the three aw values investigated. The antimicrobial efficacy of HPP against L. monocytogenes could be compromised by low aw values in food products. However, no growth of HPP-survival cells was observed during refrigerated storage in low-aw dry-cured ham, and the overexpression of virulence and stress-related genes decreased.

Mitochondrial Pentatricopeptide Repeat Protein, EMB2794, Plays a Pivotal Role in NADH Dehydrogenase Subunit nad2 mRNA Maturation in Arabidopsis thaliana.

The Arabidopsis genome encodes >450 proteins containing the pentatricopeptide repeat (PPR) motif. The PPR proteins are classified into two groups, termed as P and P Long-Short (PLS) classes. Typically, the PLS subclass proteins are mainly involved in the RNA editing of mitochondrial and chloroplast transcripts, whereas most of the analyzed P subclass proteins have been mainly implicated in RNA metabolism, such as 5' or 3' transcript stabilization and processing, splicing and translation. Mutations of PPR genes often result in embryogenesis and altered seedling developmental defect phenotypes, but only a limited number of ppr mutants have been characterized in detail. In this report, we show that null mutations in the EMB2794 gene result in embryo arrest, due to altered splicing of nad2 transcripts in the Arabidopsis mitochondria. In angiosperms, nad2 has five exons that are transcribed individually from two mitochondrial DNA regions. Biochemical and in vivo analyses further indicate that recombinant or transgenic EMB2794 proteins bind to the nad2 pre-mRNAs in vitro as well as in vivo, suggesting a role for this protein in trans-splicing of nad2 intron 2 and possibly in the stability of the second pre-mRNA of nad2. Homozygous emb2794 lines, showing embryo-defective phenotypes, can be partially rescued by the addition of sucrose to the growth medium. Mitochondria of rescued homozygous mutant plants contain only traces of respiratory complex I, which lack the NADH-dehydrogenase activity.