Smart polymers and smartphones for Betalain measurement in cooked beetroots.

Betalains in beetroots offer notable colouring properties and health benefits, including antioxidant, anti-inflammatory, hepatoprotective, and antitumorous activities. However, they degrade due to processing and storage conditions like temperature, pH, oxygen, and light-exposure. Traditional betalain determination methods are resource-intensive solid-liquid extractions. This study proposes a novel approach using a smart polymer to rapidly quantify betalains in processed beetroots. The polymer, containing N,N-dimethylaminoethyl methacrylate, selectively interacts with compounds like betalains. Characterization shows thermal stability over 250 °C and suitable mechanical properties. The film changes to colour upon interaction with betalains, allowing quantification via smartphone. The sensory polymer's efficacy was validated across 27 beetroot samples, showing no significant differences compared to traditional methods. Combining the smart polymer with a colour analysis app, "Colorimetric Titration," provides a robust and efficient means of quantifying total betalains in beetroot puree, reducing the quantification time from 180 to 90 min, promising implications for routine food industry quality assessments.

Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial.

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).

The Use of Event Related Potentials to Predict Amyloid PET Status Among Patients from a Memory Disorders Clinic.

Background: Amyloid positron emission tomography (PET) scans provide in vivo evidence of Alzheimer's disease (AD); however, their high cost limits their use in standard clinical care. Event related potentials (ERPs) may represent an inexpensive and non-invasive additional method for detecting AD pathology. Objective: We investigated whether ERPs, along with neuropsychological data, serve as predictors of amyloid PET status in patients with memory complaints. Methods: Veterans aged 50-100 were recruited from a memory disorders clinic. Participants underwent a neuropsychological battery and an ERP auditory oddball protocol. Twenty-eight patients had a positive amyloid PET scan, and thirty-nine patients had a negative scan. Results: ERP-P200 target amplitude and P200 standard latency were predictors of amyloid PET status. When submitting to ROC analysis, P200 standard latency exhibited the highest specificity and sensitivity in predicting amyloid PET positivity, correctly classifying the amyloid PET status for 86% of patients. Conclusions: ERP-P200 measures are strong indicators of amyloid-ß presence in patients from a memory disorder clinic. Increased P200 amplitude and decreased P200 latency in patients with a positive amyloid PET scan may be attributed to hyperactivation of perceptual bottom-up processes compensating for AD-related synaptic loss in the fronto-parietal networks.

Association of electronic-cigarette, number of cigarettes, and marijuana use with high-risk Human Papillomavirus (HPV) among men and women: A cross-sectional analysis of a nationally representative sample.

BACKGROUND: Smoking is associated with an increased risk of HPV infection. However, the use of e-cigarettes and marijuana, number of cigarettes, and serum cotinine concentrations in relation with HPV (6, 11, 16, 18) and high-risk HPV (16 or 18) infections in underserved and understudied populations remain poorly understood. METHODS: Data included 687 males and 664 females among whom 489 were White, 375 were Black and 342 were Hispanics from the NHANES 2013-2016 with HPV and high-risk HPV infections. Smoking history included current and past smokers, number of cigarettes, use of e-cigarettes, marijuana, and serum cotinine levels. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: High-risk HPV infection was associated with current smoking history plus ≥ 20 cigarettes/day (OR=1.92, 95 % CI=1.09, 3.37) in the overall population. E-cigarettes use (5 days) was positively associated with high-risk HPV infection (OR=2.43, 95 % CI=1.13, 5.22) in the overall population, with similar findings with e-cigarette (past 30 days) among women and Whites. CONCLUSION: High number of cigarettes, e-cigarette usage and marijuana were associated with HPV and high-risk HPV infections in the overall population. Most of these associations remained significant when stratified by gender and race/ethnicity. Increasing use of e-cigarettes and marijuana in these population warrants further investigation for the prevention of HPV infection and related cancers.

Effectiveness of a Mindfulness-Based Intervention Program to Improve Communication and Stress Coping Skills in University Students.

Investigating the contribution of mindfulness training to psychological well-being and quality of life in the university setting is of interest. The objective of the study is to present a comparative analysis of the scores in the variables of self-efficacy, resilience, coping strategies, and communication skills before and after the application of an intervention program based on mindfulness. An ex post facto cross-sectional design and a convenience sample of participants were adopted. The participants were students belonging to Education Sciences who benefited from the activities of the program. Instruments were administered to assess mindfulness, self-efficacy, resilience, coping strategies, and communication skills. The correlations of the mindfulness variable with the other psychoeducational variables evaluated were also analyzed. The results indicate an increase in the scores in the selected variables of mindfulness, resilience, communication skills, and some of the coping strategies considered productive or functional such as problem solving, self-criticism, emotional expression, desiderative thinking, social support, and cognitive restructuring. Statistically significant correlations were also observed between the variable mindfulness and those of perceived self-efficacy, resilience, coping strategies, and communication skills. The development of mindfulness training programs in the university setting is necessary to contribute to the improvement of more adaptive coping skills and the promotion of resilience.

Molecular Evaluation of the mRNA Expression of the ERG11, ERG3, CgCDR1, and CgSNQ2 Genes Linked to Fluconazole Resistance in Candida glabrata in a Colombian Population.

INTRODUCTION: The study of Candida glabrata genes associated with fluconazole resistance, from a molecular perspective, increases the understanding of the phenomenon with a view to its clinical applicability. OBJECTIVE: We sought to establish the predictive molecular profile of fluconazole resistance in Candida glabrata by analyzing the ERG11, ERG3, CgCDR1, and CgSNQ2 genes. METHOD: Expression was quantified using RT-qPCR. Metrics were obtained through molecular docking and Fisher discriminant functions. Additionally, a predictive classification was made against the susceptibility of C. glabrata to fluconazole. RESULTS: The relative expression of the ERG3, CgCDR1, and CgSNQ2 genes was higher in the fluconazole-resistant strains than in the fluconazole-susceptible, dose-dependent strains. The gene with the highest relative expression in the fluconazole-exposed strains was CgCDR1, and in both the resistant and susceptible, dose-dependent strains exposed to fluconazole, this was also the case. The molecular docking model generated a median number of contacts between fluconazole and ERG11 that was lower than the median number of contacts between fluconazole and ERG3, -CgCDR1, and -CgSNQ2. The predicted classification through the multivariate model for fluconazole susceptibility achieved an accuracy of 73.5%. CONCLUSION: The resistant strains had significant expression levels of genes encoding efflux pumps and the ERG3 gene. Molecular analysis makes the identification of a low affinity between fluconazole and its pharmacological target possible, which may explain the lower intrinsic susceptibility of the fungus to fluconazole.

Cognitive-enhanced eHealth psychosocial stepped intervention for managing breast cancer-related cognitive impairment: Protocol for a randomized controlled trial.

Introduction: Breast cancer often leads to cancer-related cognitive impairment (CRCI), which includes both objective and subjective cognitive deficits. While psychosocial interventions benefit quality of life and distress reduction, their impact on cognitive deficits is uncertain. This study evaluates the integration of a cognitive module into a digital psychosocial intervention for breast cancer patients. Methods: In this randomized controlled trial (RCT), 88 recently diagnosed breast cancer (BC) patients will receive the ICOnnecta't program (control group) - a digital stepped intervention addressing a variety of psychosocial needs. The experimental group (n = 88) will receive ICOnnecta't plus a cognitive module. Assessments at baseline, 3, 6, and 12 months will measure the interventions' impact on cognition, emotional distress, medication adherence, quality of life, post-traumatic stress, work functioning and healthcare experience. Feasibility and cost-utility analyses will also be conducted. Results: The cognitive module includes three levels. The first level contains a cognitive screening using FACT-Cog Perceived Cognitive Impairment (PCI). Patients with PCI <54 progress to a cognitive psychoeducational campus (Level 2) with content on cognitive education, behavioural strategies and mindfulness. Patients with persistent or worsened PCI (≥6) after 3 months move to Level 3, an online cognitive training through CogniFit software delivered twice a week over 12 weeks. Conclusions: This study assesses whether integrating a cognitive module into a digital psychosocial intervention improves objective and subjective cognition in breast cancer patients. Secondary outcomes explore cognitive improvement's impact on psychosocial variables. The research will contribute to testing efficacious approaches for detecting and addressing cognitive dysfunction in breast cancer patients. Trial registration: ClinicalTrials.gov, NCT06103318. Registered 26 October 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06103318?term=serra-blasco&draw=2&rank=4.

Medicinal Plant Extracts against Cardiometabolic Risk Factors Associated with Obesity: Molecular Mechanisms and Therapeutic Targets.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.

Effects of massive desiccation of olive waste residues on air quality.

New industries are proliferating in the recovery of agri-food wastes, such as those involved in the revaluation of alperujo, generated in the production of olive oil. Despite the potential environmental benefits, their activity is not exempt from new forms of emissions, aggravated by the massification of waste treatments. This work reports a six-month field campaign carried out in an alperujo desiccation plant which can serve as a proxy for these emerging industries in the Mediterranean countries. The study focused on air quality parameters, covering criteria pollutants, metals and microbiological load of particulate matter and the characterization of volatile organic compounds (VOCs). The results show a slight contribution of the factory to the NOx levels in the surroundings (3.0-12.5 µg/m3). Statistically significant effects were not observed for ozone, CO, SO2, or PM10. Concerning the levels of metals, concentrations were low and calculated health risk indexes indicated safe conditions in the area. The most abundant elements were Na (6.5 × 102 ng/m3), K (4.0 × 102 ng/m3), Al (2.7 × 102 ng/m3), Zn (2.1 × 102 ng/m3), Ca (2.16 × 102 ng/m3), Fe (3.6 × 101 ng/m3) and Mg (3.2 × 101 ng/m3). Bacterial counts, with a mean value of 15.9 CFU/m3, showed a seasonal shift, mainly explained by weather (air moisture and temperature) and PM2.5 concentration. The genomic analysis showed Cutibacterium as the dominant genus during the cold months while Bacillus predominated in the warm season. The VOCs with higher average concentrations were acetic acid (130 µg/m3), nonanoic acid (124 µg/m3), benzoic acid (29.7 µg/m3), octanoic acid (19.9 µg/m3) and nonanal (4.70 µg/m3), with the rest of compounds in concentrations below 4 µg/m3. Odorant pollutants with the greatest contribution to olfactory nuisance were aldehydes (from pentanaldehyde to decanaldehyde), acetic acid and phenol. Although the observable effects of the waste treatments were low, several parameters showed an influence on the environment which should be assessed to foresee and prevent long-term consequences.

Promoting workplace retention during global crises: An international survey of the preventive role of psychological support among victims of social discrimination in long-term care facilities.

This international cross-sectional survey examined the potential role of organizational psychological support in mitigating the association between experiencing social discrimination against long-term care (LTC) facilities' healthcare professionals (HCPs) and their intention to stay in the current workplace during the COVID-19 pandemic. Participants included a convenience sample of 2,143 HCPs (nurses [21.5 %], nurse aids or residential care workers [40.1 %], social workers [12.1 %], and others [26.4 %]) working at 223 LTC facilities in 13 countries/regions. About 37.5 % of the participants reported experiencing social discrimination, and the percentage ranged from 15.3 % to 77.9 % across countries/regions. Controlling for socio-demographic and work-related variables, experiencing social discrimination was significantly associated with a lower intention to stay, whereas receiving psychological support showed a statistically significant positive association (p-value=0.015 and <0.001, respectively). The interaction term between social discrimination and psychological support showed a statistically significant positive association with the intention to stay, indicating a moderating role of the psychological support.

Zinc-Catalyzed Cyclization of Alkynyl Derivatives: Substrate Scope and Mechanistic Insights.

Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.

Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota.

BACKGROUND: Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models. RESULTS: As expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra. CONCLUSIONS: Shotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

The New SH3b_T Domain Increases the Structural and Functional Variability Among SH3b-Like CBDs from Staphylococcal Phage Endolysins.

Endolysins, proteins encoded by phages to lyse their hosts and release their progeny, have evolved to adapt to the structural features of each host. The endolysins from Staphylococcus-infecting phages typically feature complex architectures with two enzymatically active domains (EADs) and one cell wall-binding domain (CBD) belonging to the bacterial SH3 (SH3b) superfamily. This study focuses on three SH3b-like CBDs from representative staphylococcal phage endolysins (LysRODI, LysC1C and LysIPLA5) that were structurally and functionally characterized. While RODI_CBD and C1C_CBD were assigned to the well-known SH3_5 family, a new family, SH3b_T (PF24246), was identified using the CBD from LysIPLA5 as a model. GFP-fused CBDs were created to assess their differential binding to a collection of staphylococcal strains. IPLA5_CBD showed enhanced binding to Staphylococcus epidermidis, while RODI_CBD and C1C_CBD exhibited distinct binding profiles, with RODI_CBD targeting Staphylococcus aureus specifically and C1C_CBD displaying broad binding. Sequence comparisons suggested that a few differences in key amino acids could be responsible for the latter binding difference. The CBDs modulated the activity spectrum of synthetic EAD-CBD combinations in accordance with the previous binding profiles, but in a manner that was also dependent on the EAD present in the fusion protein. These results serve as a context for the diversity and versatility of SH3b domains in staphylococcal endolysins, providing insights on how (i) the CBDs from this superfamily have diverged to adapt to diverse bacterial ligands in spite of sharing a common fold; and (ii) the evolution of specificity relies on the EAD-CBD combination rather than solely the CBD.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). METHODS AND RESULTS: This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3 months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5 L (interquartile range 0-1.6 L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21 mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P = 0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P < 0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P < 0.001) with an optimal cut-off of 1.2 L. CONCLUSIONS: VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3 months.

Microplastic pollution and nutrient enrichment shift the diet of freshwater macroinvertebrates.

Microplastic pollution poses a global threat to freshwater ecosystems, with laboratory experiments indicating potential toxic impacts through chemical toxicity, physical abrasion, and false satiation. Bioplastics have emerged as a potential greener alternative to traditional oil-based plastics. Yet, their environmental effects remain unclear, particularly at scales relevant to the natural environment. Additionally, the interactive impacts of microplastics with other environmental stressors, such as nutrient enrichment, are poorly understood and rarely studied. Under natural conditions organisms might be able to mitigate the toxic effects of microplastics by shifting their diet, but this ability may be compromised by other stressors. This study combines an outdoor mesocosm experiment and stable isotope analysis to determine changes in the trophic niches of three freshwater invertebrate species exposed to conventional (HDPE) and bio-based biodegradable (PLA) microplastics at two concentrations, both independently and combined with nutrient enrichment. Exposure to microplastics altered the isotopic niches of two of the invertebrate species, with nutrient enrichment mediating this effect. Moreover, the effects of microplastics were consistent regardless of their type or concentration. Under enriched conditions, two of the species exposed to microplastics shifted to a specialised diet compared with controls, whereas little difference was observed between the isotopic niches of those exposed to microplastic and controls under ambient nutrient conditions. Additionally, PLA was estimated to support 24 % of the diet of one species, highlighting the potential assimilation of bioplastics by biota and possible implications. Overall, these findings suggest that the toxic effects of microplastics suggested from laboratory studies might not manifest under real-world conditions. However, this study does demonstrate that subtle sublethal effects occur even at environmentally realistic microplastic concentrations. The crucial role of nutrient enrichment in mediating microplastic effects underscores the importance of considering microplastic pollution in the context of other environmental stressors.

Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.

PURPOSE: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM. METHODS: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m2) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point. RESULTS: Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P = .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primary malignancies have been reported. CONCLUSION: Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.

Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial.

The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = -34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

A Novel Foodstuff Mixture Improves the Gut-Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients.

Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.