Search

BackgroundAt interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.MethodsWe enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021.ResultsThe trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified.ConclusionsThe mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Mesofauna represents a major component of soil biological community and play a critical role in maintaining soil quality, as well as a range of ecosystem functions. A split-split plot design was performed with the aim of identifying the main predictors (phytogeographical criteria, cover type and environmental variables) of edaphic community structure under the effect of desertification. The study also aimed to examine the spatial and seasonal distribution of mesofauna community according to phytogeographical criteria (shrubland vs grassland) and cover type (bare vs covered soil) in the north-western Patagonian steppe of Argentina. The relationship between edaphic fauna, environmental variables and site location was investigated using redundancy analysis (RDA), while the main predictors of edaphic community were analysed using generalised linear mixed models (GLMMs). A total of 43 taxa of Oribatida were found in 168 samples. GLMM approaches selected cover type due to its higher effect on mesofauna community. In this sense, cover type was more important than phytogeographical criteria and environmental variables as predictor of mesofauna community. These findings contribute to a better understanding of how the distribution of mesofauna community respond in Patagonia steppe. Keywords: acari, covered soil, degradation, grassland, microarthropods, Oribatida, predictors, shrubland., Introduction Mesofauna community plays a critical role in maintaining soil quality, as well as a range of ecosystem functions (Barrios 2007). Soil invertebrates are responsible for numerous functions such as [...]

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms.

Purpose: The most common anomaly is an anomalous left coronary artery originating from the pulmonary artery. These variants can be different and depend on the location as well as how they present themselves in their anatomical distribution and their symptomatological relationship. For these reasons, this review aims to identify the variants of the coronary artery and how they are associated with different clinical conditions. Methods: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were researched until January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated using an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. Results: A total of 39 studies met the established selection criteria. In this study, 21 articles with a total of 578,868 subjects were included in the meta-analysis. The coronary artery origin variant was 1% (CI = 0.8–1.2%). For this third sample, the funnel plot graph showed an important asymmetry, with a p-value of 0.162, which is directly associated with this asymmetry. Conclusions: It is recommended that patients whose diagnosis was made incidentally and in the absence of symptoms undergo periodic controls to prevent future complications, including death. Finally, we believe that further studies could improve the anatomical, embryological, and physiological understanding of this variant in the heart.

Marine sponges represent a good source of natural metabolites for biotechnological applications in the pharmacological, cosmeceutical, and nutraceutical fields. In the present work, we analyzed the biotechnological potential of the alien species Haliclona (Halichoclona) vansoesti de Weerdt, de Kluijver & Gomez, 1999, previously collected in the Mediterranean Sea (Faro Lake, Sicily). The bioactivity and chemical content of this species has never been investigated, and information in the literature on its Caribbean counterpart is scarce. We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 µg mL−1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Through orthogonal SPE fractionations, we identified two active sphingoid-based lipid classes, also characterized by nuclear magnetic resonance and mass spectrometry, as the main components of two active fractions. Overall, our findings provide the first evaluation of the anti-cancer potential of polar lipids isolated from the marine sponge H. (Halichoclona) vansoesti, which may lead to new lead compounds with biotechnological applications in the pharmaceutical field.

Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice’s continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.

After the end-Triassic extinction, parvipelvian ichthyosaurs diversified and became dominant elements of marine ecosystems worldwide. By the Early Jurassic, they achieved a thunniform body plan that persisted for the last 100 m.y.a of their evolution. Diversification and extinctions of thunniform ichthyosaurs, and their swimming performance, have been studied from different perspectives. The transformation of limbs into hydrofoil-like structures for better control and stability during swimming predates thunniform locomotion. Despite their importance as control surfaces, fin evolution among thunnosaurs remains poorly understood. We explore ichthyosaur fin diversity using anatomical networks. Our results indicate that, under a common hydrofoil controller fin, the bone arrangement diversity of the ichthyosaur fin was greater than traditionally assumed. Changes in the connectivity pattern occurred stepwise throughout the Mesozoic. Coupled with other lines of evidence, such as the presence of a ball-and-socket joint at the leading edge of some derived Platypterygiinae, we hypothesize that fin network disparity also mirrored functional disparity likely associated with different capabilities of refined maneuvering. The ball-and-socket articulation indicates that this local point could be acting like a multiaxial intrafin joint changing the angle of attack and thus affecting the maneuverability, similar to the alula of flying birds. Further studies on large samples and quantitative experimental approaches would be worthy to test this hypothesis.

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption–desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m−2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

The present study examines the potential protective effect of familial support among first-gen Mexican descent college students regarding GPA, college persistence, and depressive symptoms. Participants included 487 Mexican descent college students from across the United States (66.7% first-gen). Results indicated that being a first-gen student was not related to the outcomes; however, family support was related to better academic and psychological outcomes (lower depressive symptoms and higher college persistence) regardless of generation status.

ObjectiveTo test the acculturation gap hypothesis by examining mother-youth value discrepancies (both acculturative and enculturative) and their association with mother-youth acculturative conflict and youth mental health outcomes.MethodParticipants were 273 Mexican descent college students attending a large, public, Hispanic Serving Institution (HSI) in West Texas (72% women). The participants' ages ranged 18-25 years (M = 19.33 years; SD = 1.54 years).ResultsThree models assessed the relationship between mother-youth value discrepancies and mental health outcomes (suicidal ideation, non-suicidal self-injury, and depressive symptoms) as mediated by mother-youth acculturative conflict. Consistently, Mexican heritage cultural values were related to mental health outcomes while American cultural values were not.ConclusionsThe study found that increased mother-youth discrepancies on Mexican cultural values were associated with increased negative mental health outcomes. Our findings suggest that adopting or learning new mainstream American values does not substitute for the Mexican cultural values that protect against negative outcomes.

This paper examines whether using "From Here to There!" ("FH2T:E"), a dynamic game-based mathematics learning technology relates to improved early algebraic understanding. We use student log files within FH2T to explore the possible benefits of student behaviors and gamification on learning gains. Using in app measures of student interactions (mouse clicks, resets, errors, problem solving steps, and completions), 19 variables were identified to summarize overall problem solving processes. An exploratory factor analysis identified five clear factors including engagement in problem solving, progress, strategic flexibility, strategic efficiency, and speed. Regression analyses reveal that after accounting for behavior within the app, playing the gamified version of the app contributed to higher learning gains than playing a nongamified version. Next, completing more problems within the game related to higher achievement on the post-test. Third, two significant interactions were found between progress and prior knowledge and engagement in problem solving and prior knowledge, where low performing students gained more when they completed more problems and engaged more with those problems. [This article was published in "Educational Technology Research and Development" (EJ1208101).]