Metataxonomic Analysis of Milk Samples From SARS-CoV-2-Positive and SARS-CoV-2-Negative Women.

Objective: To assess the impact of SARS-CoV-2 viral infection on the metataxonomic profile and its evolution during the first month of lactation. Methods: Milk samples from 37 women with full-term pregnancies and mild SARS-CoV-2 infection and from 63 controls, collected in the first and fifth postpartum weeks, have been analyzed. SARS-CoV-2 RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) both in cases and controls. After DNA extraction, the V3-V4 hypervariable region of the gene 16S rRNA was amplified and sequenced using the MiSeq system of Illumina. Data were submitted for statistical and bioinformatics analyses after quality control. Results: All the 1st week and 5th week postpartum milk samples were negative for SARS-CoV-2 RNA. Alpha diversity showed no differences between milk samples from the study and control group, and this condition was maintained along the observation time. Analysis of the beta-diversity also indicated that the study and control groups did not show distinct bacterial profiles. Staphyloccus and Streptococcus were the most abundant genera and the only ones that were detected in all the milk samples provided. Disease state (symptomatic or asymptomatic infection) did not affect the metataxonomic profile in breast milk. Conclusion: These results support that in the non-severe SARS-CoV-2 pregnant woman infection the structure of the bacterial population is preserved and does not negatively impact on the human milk microbiota.

Immediate Pre-Partum SARS-CoV-2 Status and Immune Profiling of Breastmilk: A Case-Control Study.

Objetive: To address the prevalence of SARS-CoV-2 and the evolutionary profile of immune compounds in breastmilk of positive mothers according to time and disease state. Methods: Forty-five women with term pregnancies with confirmed non-severe SARS-CoV-2 infection (case group), and 96 SARS-CoV-2 negative women in identical conditions (control group) were approached, using consecutive sample. Weekly (1st to 5th week postpartum) reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs (cases) and breastmilk (cases and controls) were obtained. Concentration of cytokines, chemokines, and growth factors in breastmilk (cases and controls) were determined at 1st and 5th week post-partum. Results: Thirty-seven (study group) and 45 (control group) women were enrolled. Symptomatic infection occurred in 56.8% of women in the study group (48% fever, 48% anosmia, 43% cough). SARS-CoV-2 RNA was not found in breastmilk samples. Concentrations of cytokines (IFN-γ, IL-1ra, IL-4, IL-6, IL-9, IL-13, and TNF-α) chemokines (eotaxin, IP-10, MIP-1α, and RANTES) and growth factors (FGF, GM-CSF, IL7, and PDGF-BB) were higher in breastmilk of the study compared with the control group at 1st week postpartum. Immune compounds concentrations decreased on time, particularly in the control group milk samples. Time of nasopharyngeal swab to become negative influenced the immune compound concentration pattern. Severity of disease (symptomatic or asymptomatic infection) did not affect the immunological profile in breast milk. Conclusions: This study confirms no viral RNA and a distinct immunological profile in breastmilk according to mother's SARS-CoV-2 status. Additional studies should address whether these findings indicate efficient reaction against SARS-CoV-2 infection, which might be suitable to protect the recipient child.

Consumption of Ultra-Processed Food and Drinks and Chronic Lymphocytic Leukemia in the MCC-Spain Study.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Its etiology is largely unknown but increasing incidence rates observed worldwide suggest that lifestyle and environmental factors such as diet might play a role in the development of CLL. Hence, we hypothesized that the consumption of ultra-processed food and drinks (UPF) might be associated with CLL. Data from a Spanish population-based case-control study (MCC-Spain study) including 230 CLL cases (recruited within three years of diagnosis) and 1634 population-based controls were used. The usual diet during the previous year was collected through a validated food frequency questionnaire and food and drink consumption was categorized using the NOVA classification scheme. Logistic regression models adjusted for potential confounders were used. Overall, no association was reported between the consumption of UPF and CLL cases (OR per each 10% increase of the relative contribution of UPF to total dietary intake = 1.09 (95% CI: 0.94; 1.25)), independently of the Rai stage at diagnosis. However, when analyses were restricted to cases diagnosed within <1 year (incident), each 10% increment in the consumption of UPF was associated with a 22% higher odds ratio of CLL (95% CI: 1.02, 1.47) suggesting that the overall results might be affected by the inclusion of prevalent cases, who might have changed their dietary habits after cancer diagnosis. Given the low number of cases in the subgroup analyses and multiple tests performed, chance findings cannot totally be ruled out. Nonetheless, positive associations found in CLL incident cases merit further research, ideally in well-powered studies with a prospective design.

Occupational Exposure to Pesticides and Chronic Lymphocytic Leukaemia in the MCC-Spain Study.

We aimed to study the association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) in Spain. Occupational exposure to pesticides (four insecticides, four herbicides and two fungicides) was evaluated using a job-exposure matrix for the Spanish population (MatEmESp) among 302 CLL cases and 1567 population controls in five regions of Spain, 2010-2013. Cumulative exposure scores (CES) were obtained by summing across the exposed jobs the product of prevalence, intensity and duration of exposure to each active substance. Principal components analysis (PCA) and logistic regression models adjusted for age, sex, region, education and occupational exposure to solvents were used. Around 20% of controls and 29% of cases were exposed to one or more pesticides. Compared to non-exposed, subjects in the highest tertile (3rd tertile) of CES of insecticides, herbicides, fungicides were more likely to have CLL [OR (95% CI), P-trend; 2.10 (1.38; 3.19), 0.002; 1.77 (1.12; 2.80), 0.12; and 1.67 (1.06; 2.64), 0.10, respectively). Following PCA, the first component (PC1, explaining 70% of the variation) equally led by seven active substances (the insecticide pyrethrin, all herbicides, all fungicides) was associated with a 26% higher odds of having CLL for 1-standard deviation increase in PC1 (95% CI: 1.14 to 1.40). These results confirm previous associations between CLL and exposure to pesticides and provide additional evidence by application groups and active substance. However, more research is needed to disentangle independent effects of individual active substances.

Adherence to the 2018 WCRF/AICR cancer prevention guidelines and chronic lymphocytic leukemia in the MCC-Spain study.

INTRODUCTION: Preventable risk factors for chronic lymphocytic leukemia (CLL) remain largely unknown. The aim of this study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and CLL, in the MCC-Spain case-control study. METHODS: A total of 318 CLL cases and 1293 population-based controls were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on the 2018 recommendations for cancer prevention (on body fatness, physical activity, and diet) was constructed. We used logistic regression analysis adjusting for potential confounders. RESULTS: Individuals in the highest tertile of the WCRF/AICR score had an odds ratio for CLL of 1.25 (95 % CI 0.91; 1.73) compared with individuals with low adherence (p-trend = 0.172). Each point increment in the score was associated with an OR for CLL of 1.06 (95 % CI 0.91; 1.23). Analyses by severity of disease did not show significant heterogeneity of effects. CONCLUSION: Overall, our results do not support an association between the WCRF/AICR score and CLL, yet we might have been limited by statistical power and study design to detect modest associations. Further research, ideally with a prospective design, long follow-up, and including additional lymphoma subtypes, is warranted to confirm the impact of composite healthy lifestyle behaviors on lymphoma risk.

The Dietary Inflammatory Index and Chronic Lymphocytic Leukaemia in the MCC Spain Study.

Chronic inflammation plays a role in the development of chronic lymphocytic leukaemia (CLL), and diet might modulate chronic inflammation. This study aims to evaluate the association between the dietary inflammatory index (DII®) and CLL. A total of 366 CLL cases and 1643 controls of the Spanish multicase-control (MCC) Spain study were included. The inflammatory potential of the diet was assessed using the energy-adjusted dietary inflammatory index (E-DII) based on 30 items from a validated semi-quantitative food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for potential confounders. Overall, a modest, non-statistically significant, positive association was observed between CLL and E-DII scores (OR for a one-unit increase in E-DII: 1.05 (CI 95%: 0.99, 1.12), p-value = 0.09 and by tertiles: ORT2vsT1: 1.20 (CI 95%: 0.90, 1.59); OR T3vsT1: 1.21 (CI 95%: 0.90, 1.62), p trend = 0.21). These results were independent from disease severity (p-het: 0.70), time from diagnosis (p-het: 0.67) and CLL treatment received (p-het: 0.56). No interactions were detected. In conclusion, the consumption of a diet with high pro-inflammatory components was not significantly associated with CLL. Changes towards a more pro-inflammatory dietary pattern in younger generations not included here warrant future research.

Photocatalytic Mechanisms for Peroxymonosulfate Activation through the Removal of Methylene Blue: A Case Study.

Industrial activity is one of the most important sources of water pollution. Yearly, tons of non-biodegradable organic pollutants are discharged, at the least, to wastewater treatment plants. However, biological conventional treatments are unable to degrade them. This research assesses the efficiency of photocatalytic activation of peroxymonosulfate (PMS) by two different iron species (FeSO4 and Fe3+-citrate) and TiO2. These substances accelerate methylene blue removal by the generation of hydroxyl and sulfate radicals. The required pH and molar ratios PMS:Fe are crucial variables in treatment optimization. The kinetic removal is reduced by the appearance of scavenger reactions in acidic and basic conditions, as well as by the excess of PMS or iron. The best performance is achieved using an Fe3+-citrate as an iron catalyst, reaching the total removal of methylene blue after 15 min of reaction, with a molar ratio of 3.25:1 (1.62 mM of PMS and 0.5 mM Fe3+-citrate). Fe3+-citrate reached higher methylene blue removal than Fe2+ as a consequence of the photolysis of Fe3+-citrate. This photolysis generates H2O2 and a superoxide radical, which together with hydroxyl and sulfate radicals from PMS activation attack methylene blue, degrading it twice as fast as Fe2+ (0.092 min-1 with Fe2+ and 0.188 min-1 with Fe3+-citrate). On the other hand, a synergistic effect between PMS and titanium dioxide (TiO2) was observed (SPMS/TiO2/UV-A = 1.79). This synergistic effect is a consequence of PMS activation by reaction with the free electron on the surface of TiO2. No differences were observed by changing the molar ratio (1.04:1; 0.26:1 and 0.064:1 PMS:TiO2), reaching total removal of methylene blue after 80 min of reaction.

Dichotomization of the new revised international prognostic scoring system for a better clinical stratification of patients with myelodysplastic syndromes.

In clinical practice, patients with myelodysplastic syndromes (MDS) are usually classified in low or high-risk groups to take therapeutic decisions, conservative for low-risk, whereas active for high-risk. Nevertheless, in the Revised International Prognostic Scoring System (IPSS-R) is not well stated which patients are low or high-risk. This study was aimed to ascertain in 364 MDS patients which IPSS-R threshold better dichotomized in low vs. high-risk. The best dichotomization was obtained with an IPSS-R cut-point of 3. Accordingly, 68% patients were classified as low-risk (median OS, 61.3 months) and 32% as high-risk MDS (median OS, 13.9 months) (p < .001). Interestingly, the intermediate IPSS-R risk patients presented an OS more related to the high IPSS-R than to the low IPSS-R risk group. In conclusion, an IPSS-R cut-point of 3 led to a meaningful stratification in low and high-risk that can be helpful for the clinical management of MDS patients.

Proteomic analysis of Lactobacillus pentosus for the identification of potential markers of adhesion and other probiotic features.

We analyzed the adhesion capacity to mucus of 31 Lactobacillus pentosus strains isolated from naturally fermented Aloreña green table olives using an immobilized mucin model. On the basis of their adhesive capacity to mucin, three phenotypes were selected for cell-wall protein proteomic analysis to pinpoint proteins involved in the adhesion process: the highly adhesive L. pentosus CF1-43 N (73.49% of adhesion ability), the moderately adhesive L. pentosus CF1-37 N (49.56% of adhesion ability) and the poorly adhesive L. pentosus CF2-20P (32.79% of adhesion ability). The results revealed four moonlighting proteins over-produced in the highly adhesive L. pentosus CF1-43 N, which were under/not produced in the other two L. pentosus strains (CF1-37 N and CF2-20P). These proteins were involved in glycolytic pathway (phosphoglycerate mutase and glucosamine-6-phosphate deaminase), stress response (small heat shock protein) and transcription (transcription elongation factor GreA). Furthermore, the relative fold change in gene expression analysis showed significant up-regulation of the genes coding for these four moonlighting proteins in the highly adhesive L. pentosus CF1-43 N versus the poorly adhesive L. pentosus CF2-20P and also in response to mucin for 20 h which clearly indicate the significant role of these genes in the adhesion capacity of L. pentosus. Thus, these proteins could be used as biomarkers for mucus adhesion in L. pentosus. On the other hand, mucin exposure induced other probiotic effects in L. pentosus strains, enhancing their co-aggregation ability with pathogens and possible inactivation.

Adherence to the Western, Prudent, and Mediterranean dietary patterns and chronic lymphocytic leukemia in the MCC-Spain study.

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings.

Efficacy of "HLE"-a multidrug efflux-pump inhibitor-as a disinfectant against surface bacteria.

We evaluated the efficacy of a new disinfectant product, HLE, to inhibit multiple species of planktonic and biofilm bacterial cultures. The HLE disinfectant comprised of EDTA, lactic acid and hydrogen peroxide, and our data indicated that the disinfectant had effective antimicrobial and anti-biofilm activity even at low concentrations (0.15% to 0.4% HLE, v/v). Furthermore, the HLE disinfectant destabilized biofilm structures eradicated them due to the synergistic effect of EDTA and both antimicrobials (lactic acid and hydrogen peroxide), as revealed by confocal laser scanning microscopy. Additionally, sub-inhibitory concentrations of HLE disinfectant, with EDTA as an efflux pump inhibitor, inhibited the expression of multidrug EfrAB, NorE and MexCD efflux pumps in both planktonic and biofilm cultures. This could provide an alternative way to disinfect surfaces to avoid spreading multi-drug resistant strains in the food chain and the environment by decreasing efflux pump expression and consequently reducing the antibiotic selective pressure caused by systemic antibiotics and disinfectant use.

Established and suggested exposures on CLL/SLL etiology: Results from the CLL-MCC-Spain study.

INTRODUCTION: Chronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLL METHODS: Using the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions. RESULTS: Among the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend<0.016) and for type II diabetes. CONCLUSION: We confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted.

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: insights from the canadian biomarker integration network in depression.

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We present the insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multi-project network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies.

Maximization of monomeric C5 sugars from wheat bran by using mesoporous ordered silica catalysts.

The hydrolysis process of a real fraction of arabinoxylans derived from wheat bran was studied. The influence of catalyst type and loading, reaction time and different metal cations were discussed in terms of the hydrolysis yield of arabinose and xylose oligomers as well as the formation of furfural as degradation product. A high yield of arabinoxylans into the corresponding monomeric sugars (96 and 94% from arabino- and xylo-oligosaccharides, respectively) was obtained at relatively high temperatures (180°C) and short reaction times (15min) with a catalyst loading of 4.8g of RuCl3/Al-MCM-48 per g of initial carbon in hemicelluloses.

Extraction of arabinoxylans from wheat bran using hydrothermal processes assisted by heterogeneous catalysts.

The extraction/hydrolysis process of arabinoxylans from destarched wheat bran was studied in this work using different mesoporous silica supports and the corresponding RuCl3-based catalysts. The effects of temperature, time, catalyst supports and ruthenium catalysts were investigated and discussed in terms of the arabinoxylans extraction yield and their polymerization degree. Relatively high temperatures (180°C), short extraction times (10min) and RuCl3 supported on Al-MCM-48 led to a high amount of extracted arabinoxylans (78%) with a low molecular weight (9kDa). Finally, a relation between the operating conditions, the arabinoxylans extraction yield and the molecular weight was stablished based on the obtained results.

Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia.

PURPOSE: There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic variability in vitamin C transporter gene SLC23A2 could explain some inconsistencies in the literature. METHODS: Fruit/vegetable/vitamin C consumption from food frequency questionnaires and six low-penetrance genetic susceptibility polymorphisms in vitamin C transporter gene SLC23A2 (rs1715364, rs6133175, rs1776948, rs6139587, rs369270 and rs6052937) were examined in 434 CLL cases and 1257 randomly selected controls from primary care centres with genetic data of whom 275 cases and 1094 controls having both diet and genetic information. Logistic regression models were used to estimate odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: CLL patients were more likely to have a higher fruit consumption than controls (highest versus lowest quartile in g/day OR: 1.48; 95 % CI: 1.00 to 2.18; P = 0.03), whereas no associations were found with vegetable or total vitamin C intake. Based on log-additive models, rs6133175_A > G (OR: 1.19, 95 % CI: 1.00 to 1.41; P = 0.05) and rs1776948_T > A (OR: 1.20; 95 %CI: 1.01 to 1.41; P = 0.04) were associated with CLL. The haplogenotype analysis (rs1715364, rs6133175) supported the genotype results. No gene-diet interactions in CLL remained statistically significant after correction for multiple testing. CONCLUSIONS: These data suggest that both fruit intake and genetic marker in SLC23A2 may play an independent role in CLL biology.

CD34 expression and the outcome of nucleophosmin 1-mutated acute myeloid leukemia.

CD34 positivity has been considered as an adverse prognostic factor in acute myeloid leukemia (AML). Although nucleophosmin 1-mutated (NPM1m) AML is usually CD34 negative, this marker may be expressed at diagnosis or acquired at relapse in a variable number of cases. Our objective was to ascertain if CD34 expression has any influence on the general outcome of this form of acute leukemia. Analysis of clinical outcome (complete remissions, relapses, disease-free survival, and overall survival) was performed depending on the degree of expression of CD34 determined by flow cytometry, in 67 adult patients with NPM1m AML. CD34 expression did not have any influence on the variables analyzed whatever the percentage of blasts expressing this marker. In contrast to other forms of AML, CD34 expression is not an unfavorable prognostic factor in NPM1m AML, neither at diagnosis nor at relapse.

Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates.

In order to improve the efficiency of the anti-inflammatory drug ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen at their periphery or at their focal point, respectively, have been synthesized, and the release of the drug was studied using HPLC. Macrophages were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated dendritic systems and compared with mixtures of non-ibuprofen dendritic systems in the presence of the drug. The cationic ibuprofen-conjugated dendron was the compound that showed higher anti-inflammatory properties. It reduces the LPS-induced COX-2 expression and decreases the release of several inflammatory cytokines such as TNFα, IL-1ß, IL-6, and CCL3. These results open new perspectives in the use of these compounds as drug carriers.

Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features.

Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.