Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants.

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Geriatric conditions and invasive management in frail patients with NSTEMI. A subgroup analysis of a randomized clinical trial.

INTRODUCTION AND OBJECTIVES: Invasive management in frail patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains controversial. We investigated the impact of various geriatric conditions. METHODS: The MOSCA-FRAIL trial included 167 adults aged ≥ 70 years with frailty (Clinical Frailty Scale [CFS] ≥ 4 points) and NSTEMI, who were randomized to either an invasive (n = 84) or conservative (n = 83) strategy. In addition to frailty, we measured activities of daily living (Barthel index), cognitive impairment (Pfeiffer test), and comorbidities (Charlson index). The primary endpoint was the difference (invasive minus conservative) in restricted mean survival time (RMST) for all-cause mortality at a median follow-up of 3.9 years. RESULTS: A total of 93 patients died. The RMST difference favored invasive management at the CFS 25th percentile (CFS = 4; 157 days, 95%CI, 18-295; P = .027), which changed to a nonsignificant effect at the 50th and 75th percentiles. The RMST difference remained nonsignificant, irrespective of the severity of other geriatric assessments. In time-to-event analysis, invasive management was associated with an initially lower life expectancy, peaking at around 1 year, among all subgroups. However, patients with CFS = 4 experienced a benefit at the end of follow-up (181 days, 95%CI, 19-343), whereas those with CFS > 4 did not (-16 days, 95%CI, -217 to 186; interaction P = .16). Subgroups defined by other geriatric markers showed a similar time-dependent trend, albeit with weaker statistical interaction. CONCLUSIONS: Among adults with frailty and NSTEMI, the CFS might be useful for evaluating the relative risks and benefits of invasive management. A CFS > 4 could serve as a valuable threshold for decision-making.

One sampler to see it all: The use of APIStrips for beehive characterization and pesticide residue evaluation based on mass spectrometry.

Environmental monitoring is crucial for assessing the overall state of the ecosystems in terms of contaminant impact and chemical landscape. The use of honey bee (Apis mellifera) colonies considerably eases the sampling activities, as honey bees are exposed to a wide range of substances that are transported and accumulated within the beehives. In this work, combining low-resolution and high-resolution mass spectrometry, the APIStrip passive sampler has been employed to evaluate the presence of pesticide residues and the overall characterization of beehive environments. A total of 180 APIStrips have been deployed in 10 Danish apiaries, located in different landscapes, during a five-month sampling period. The targeted methodology for pesticide analysis was based on gas and liquid chromatography coupled with triple quadrupole mass spectrometry, covering 430 pesticide residues. A total of 29 pesticide residues were identified (fluopyram and azoxystrobin being the most frequently detected), with remarkable differences in the pesticide load between apiaries. For its part, the use of non-targeted approaches through liquid chromatography coupled with an Orbitrap mass spectrometer allowed the detection of unknown compounds that were specific of certain environments. Natural products such as eupatilin and gnaphaliin, which are derived from plant sources, were present exclusively in one of the apiaries. Additionally, the detection of drimane sesquiterpenoids, including compounds potentially originating from the Aspergillus genus, suggests the capability of APIStrips to early detect fungal contamination within beehives. This dual approach of low- and high-resolution mass spectrometry maximizes the analytical potential of APIStrips as a tool capable of detecting a wide range of substances with implications for both agricultural practices and ecological health.

Mn-ferrite nanoparticles as promising magnetic tags for radiofrequency inductive detection and quantification in lateral flow assays.

Lateral flow assays are low-cost point-of-care devices that are stable, easy to use, and provide quick results. They are mostly used as qualitative screening tests to detect biomarkers for several diseases. Quantification of the biomarkers is sometimes desirable but challenging to achieve. Magnetic nanoparticles can be used as tags, providing both visual and magnetic signals that can be detected and quantified by magnetic sensors. In the present work, we synthesized superparamagnetic MnFe2O4 nanoparticles using the hydrothermal coprecipitation route. MnFe2O4 presents low magnetic anisotropy and high saturation magnetization, resulting in larger initial magnetic susceptibility, which is crucial for optimizing the signal in inductive sensors. We functionalized the coprecipitated nanoparticles with citric acid to achieve colloidal stability in a neutral pH and to provide carboxyl groups to their surface to bioconjugate with biomolecules, such as proteins and antibodies. The nanomaterials were characterized by several techniques, and we correlated their magnetic properties with their sensitivity and resolution for magnetic detection in radiofrequency inductive sensors. We considered the NeutrAvidin/biotin model of biorecognition to explore their potential as magnetic labels in lateral flow assays. Our results show that MnFe2O4 nanoparticles are more sensitive to inductive detection than magnetite nanoparticles, the most used nanotags in magnetic lateral flow assays. These nanoparticles present high potential as magnetic tags for the development of sensitive lateral flow immunoassays for detecting and quantifying biomarkers.

Outcomes of Bariatric Surgery in Patients with Schizophrenia.

BACKGROUND: Outcomes of bariatric surgery (BS) in patients with schizophrenia are poorly understood. We aimed to analyze the effects of BS in patients with schizophrenia (SZ) or schizoaffective disorder (SZA). METHODS: This was a multicenter, retrospective case-control study in patients with SZ or SZA who had undergone BS in seven public referral hospitals in Spain. Controls without psychiatric comorbidity were selected in a 1:4 ratio. Detailed clinical and biochemical data were collected preoperatively and at 12, 24, 36, 48, and 60 months after BS. RESULTS: Twenty patients with SZ (n = 15; 75%) or SZA (n = 5; 25%) and 80 matched controls were studied. There were no differences between patients and controls concerning the evolution of the percentage of total weight loss. The remission rate of the main comorbidities was similar between groups except for hypertension, which was lower in patients with a psychotic disorder from year 3. There were no mortalities within 30 days of surgery in either group. The psychiatric medication burden did not change during follow-up. CONCLUSIONS: BS is safe and effective in carefully selected patients with SZ. The course of the psychiatric disease does not seem to be worsened by the procedure.

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma.

BACKGROUND: Helicobacter pylori (H. pylori) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial. AIM: To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital. METHODS: We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded. RESULTS: A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant (n = 47, 52.8%), followed by squamous cell carcinoma (n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment. CONCLUSION: In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

PIM1 is a potential therapeutic target for the leukemogenic effects mediated by JAK/STAT pathway mutations in T-ALL/LBL.

Precursor T-cell neoplasms (T-ALL/LBL) are aggressive hematological malignancies that arise from the malignant transformation of immature thymocytes. Despite the JAK/STAT pathway is recurrently altered in these neoplasms, there are not pharmacological inhibitors officially approved for the treatment of T-ALL/LBL patients that present oncogenic JAK/STAT pathway mutations. In the effort to identify potential therapeutic targets for those patients, we followed an alternative approach and focused on their transcriptional profile. We combined the analysis of molecular data from T-ALL/LBL patients with the generation of hematopoietic cellular models to reveal that JAK/STAT pathway mutations are associated with an aberrant transcriptional profile. Specifically, we demonstrate that JAK/STAT pathway mutations induce the overexpression of the PIM1 gene. Moreover, we show that the pan-PIM inhibitor, PIM447, significantly reduces the leukemogenesis, as well as the aberrant activation of c-MYC and mTOR pathways in cells expressing different JAK/STAT pathway mutations, becoming a potential therapeutic opportunity for a relevant subset of T-ALL/LBL patients.

Enhanced Genomic and Transcriptomic Resources for Trichinella pseudospiralis and T. spiralis to Underpin the Discovery of Molecular Differences between Stages and Species.

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host-parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin-with possible roles in modulating host immune responses and facilitating parasite survival-were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella-host interactions might offer possible avenues for developing new interventions against trichinellosis.

Multinational evaluation of genetic diversity indicators for the Kunming-Montreal Global Biodiversity Framework.

Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.

A PCR Test Using the Mini-PCR Platform and Simplified Product Detection Methods Is Highly Sensitive and Specific to Detect Fasciola hepatica DNA Mixed in Human Stool, Snail Tissue, and Water DNA Specimens.

Fasciola hepatica has a complex lifecycle with multiple intermediate and definitive hosts and influenced by environmental factors. The disease causes significant morbidity in children and its prevalent worldwide. There is lack of data about distribution and burden of the disease in endemic regions, owing to poor efficacy of the different diagnostic methods used. A novel PCR-based test was developed by using a portable mini-PCR® platform to detect Fasciola sp. DNA and interpret the results via a fluorescence viewer and smartphone image analyzer application. Human stool, snail tissue, and water samples were used to extract DNA. Primers targeting the ITS-1 of the 18S rDNA gene of Fasciola sp. were used. The limit of detection of the mini-PCR test was 1 fg/µL for DNA samples diluted in water, 10 fg/µL for Fasciola/snail DNA scramble, and 100 fg/µL for Fasciola/stool DNA scramble. The product detection by agarose gel, direct visualization, and image analyses showed the same sensitivity. The Fh mini-PCR had a sensitivity and specificity equivalent to real-time PCR using the same specimens. Testing was also done on infected human stool and snail tissue successfully. These experiments demonstrated that Fh mini-PCR is as sensitive and specific as real time PCR but without the use of expensive equipment and laboratory facilities. Further testing of multiple specimens with natural infection will provide evidence for feasibility of deployment to resource constrained laboratories.

Components of hot and cold executive functions and their relations to different forms of stress resilience: A systematic review.

Increasing evidence points out that Executive Functions (i.e., EFs) may be core mechanisms for the generation of resilient responses to adversity. A systematic review testing the relations between either affective (hot) and/or non-affective (cold) EFs (i.e., inhibition, flexibility and working memory updating) and resilience was conducted. A total of 449 articles were initially identified. After two steps of title-and-abstract (k = 449), and full-text reading filtering (k = 67), 11 studies were reviewed. Three studies included cold measures of working memory and supported significant positive relations between higher working memory functioning and higher trait resilience levels. One study included cold measures of inhibition and another one both hot and cold measures, with only the first one supporting a positive relation between more efficient inhibition and higher trait resilience levels. Finally, 7 studies measured flexibility in its cold and/or hot dimensions and overall supported significant relations between higher flexibility and higher levels of trait, process and outcome resilience measures. These results support the role of EFs performance to promote different forms of resilience. This review allows to identify different issues that need to be addressed in future research and highlight the need to integrate the analysis of all hot and cold EFs components to understand their role in the generation of resilience.

Critical Factors Affecting the Selective Transformation of 5-Hydroxymethylfurfural to 3-Hydroxymethylcyclopentanone Over Ni Catalysts.

The ring-rearrangement of 5-hydroxymethylfurfural (HMF) to 3-hydroxymethylcyclopentanone (HCPN) was investigated over Ni catalysts supported on different carbon supports and metallic oxides with different structure and acid-base properties. Their catalytic performance was tested in a batch stirred reactor in aqueous solution at 180 °C and 30 bar of H2. Under these conditions, the HMF hydrogenation proceeds through three possible competitive routes: (i) a non-water path leading to the total hydrogenation product, 2,5-di-hydroxymethyl-tetrahydrofuran (DHMTHF), and two parallel acid-catalyzed water-mediated routes responsible for (ii) ring-opening and (iii) ring-rearrangement reaction products. All catalyst systems primarily produced HCPN, but reaction rates and product distribution were influenced by several variables, some of them intensely analyzed in this work. The most proper conditions resulted to be the presence of the medium/strong Lewis's acidity of a Ni/ZrO2 catalyst (initial TOF=5.99 min-1 and 73 % HCPN selectivity) or the Brønsted acidity originated by an oxidized high surface area graphite, Ni/HSAG-ox (initial TOF=5.92 min-1 and 87 % HCPN selectivity). However, too high density of acidic sites on the catalyst support (Ni/Al2O3) and sulfur impurities from the HMF feedstock led to catalyst deactivation by coke deposition and Ni poisoning, respectively.

+Ciencia: a training program to increase evidence-based science communication and literacy for Hispanic high school and undergraduate students.

Science misinformation represents a significant challenge for the scientific community. Hispanic communities are particularly vulnerable due to language barriers and the lack of accessible information in Spanish. We identified that a key step toward enhancing the accessibility of information for non-native English-speaking communities involves imparting science communication education and training to Hispanic youth. Our goal was to provide them with the skills to become science ambassadors who can effectively engage with their communities and bridge communication gaps. To address this, we developed the first science communication training program in Spanish for Hispanic high school and undergraduate students in Puerto Rico. The program called +Ciencia aims to provide training and education on science communication for Hispanic minorities through experiential and collaborative learning. In the short term, our multifaceted approach works to counter misinformation and promote science literacy within the broader community. Over the long term, our grassroots efforts with students will evolve into a generation of professionals equipped with strong engagement skills and comprehensive training in science communication with a specific focus on Hispanic audiences. Herein, we describe the components of this educational program and provide open access to educational materials and articles developed by three cohorts.

Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages.

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.

Towards the valorisation of glycerol by designing the surface chemistry of carbon xerogels by doping and oxygen functionalization.

Research on innovative approaches to the valorisation of glycerol as a subproduct of biodiesel production has acquired an increasing demand in the development of a circular economy around energy generation, especially, in the line of improvement of the heterogeneous metallic catalysts used. In this regard, carbon xerogels have gained importance due to their stability and modifiability, while transition metals such as copper stand out as a cost-effective alternative, resulting in a technology where surface engineering plays a crucial role in achieving competitive catalytic activity. Building upon this, current research evaluates doped xerogels (Si, N, or GO) as supports of Cu and catalysts by themselves for glycerol oxidation. Benefits from the incorporation of oxygenated functional groups (OFG) were also evaluated. Results showed a consistently higher selectivity towards lactic acid (LA) across all catalysts and competitive catalytic conversion. In this performance, dopants played a crucial role in surface acid-base characteristics, while oxygenated functional groups (OFG) influenced copper adsorption, dispersion, and reducibility. Notably, the Cu/CXN-f catalyst demonstrated the highest LA yield by combining the effect of N as a doping species, with the presence of OFG and the formation of appropriated metallic Cu domains. This research underscores the potential of carbon xerogels in the tailored catalyst design, contributing to sustainable chemical production through their customizable textural and chemical properties.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.