Genome Report: First reference genome of Vaccinium floribundum Kunth, an emblematic Andean species.

Vaccinium floribundum Kunth, known as "mortiño, " is an endemic shrub species of the Andean region adapted to harsh conditions in high-altitude ecosystems. It plays an important ecological role as a pioneer species in the aftermath of deforestation and human-induced fires within paramo ecosystems, emphasizing its conservation value. While previous studies have offered insights into the genetic diversity of mortiño, comprehensive genomic studies are still missing to fully understand the unique adaptations of this species and its population status, highlighting the importance of generating a reference genome for this plant. ONT and Illumina sequencing were used to establish a reference genome for this species. Three different de novo genome assemblies were generated and compared for quality, continuity and completeness. The Flye assembly was selected as the best and refined by filtering out short ONT reads, screening for contaminants and genome scaffolding. The final assembly has a genome size of 529 MB, containing 1,317 contigs and 97% complete BUSCOs, indicating a high level of integrity of the genome. Additionally, the LAI Index of 12.93, further categorizes this assembly as a reference genome. The genome of V. floribundum reported in this study is the first reference genome generated for this species, providing a valuable tool for further studies. This high-quality genome, based on the quality and completeness parameters obtained, will not only help uncover the genetic mechanisms responsible for its unique traits and adaptations to high-altitude ecosystems, but will also contribute to conservation strategies for a species endemic to the Andes.

Excess weight and changes in body composition in boys and girls from La Plata district (Buenos Aires, Argentina) - a study with a secular perspective.

The aim of the present study was to advance knowledge of the secular changes in the prevalence of excess weight (overweight and obesity) and body composition of children living in different localities of La Plata district (Buenos Aires province, Argentina) over the last two decades. For this purpose, anthropometric data and information on the socioeconomic and environmental context of residence of schoolchildren aged 4.0-12.9 years collected during 2005-2009 (Cohort 1, n = 1 233) and 2016-2019 (Cohort 2, n = 1 499) were analysed and compared. From a secular perspective, the current analysis showed that the socioeconomic and environmental conditions of families living in La Plata district have deteriorated in recent decades. In this context, child excess weight increased by 13% and body composition was altered, mainly as a result of an increase in fat mass, without observing changes in the muscle component.

The prognostic relevance of a gene expression signature in MRI-defined highly vascularized glioblastoma.

Background: The vascular heterogeneity of glioblastomas (GB) remains an important area of research, since tumor progression and patient prognosis are closely tied to this feature. With this study, we aim to identify gene expression profiles associated with MRI-defined tumor vascularity and to investigate its relationship with patient prognosis. Methods: The study employed MRI parameters calculated with DSC Perfusion Quantification of ONCOhabitats glioma analysis software and RNA-seq data from the TCGA-GBM project dataset. In our study, we had a total of 147 RNA-seq samples, which 15 of them also had MRI parameter information. We analyzed the gene expression profiles associated with MRI-defined tumor vascularity using differential gene expression analysis and performed Log-rank tests to assess the correlation between the identified genes and patient prognosis. Results: The findings of our research reveal a set of 21 overexpressed genes associated with the high vascularity pattern. Notably, several of these overexpressed genes have been previously implicated in worse prognosis based on existing literature. Our log-rank test further validates that the collective upregulation of these genes is indeed correlated with an unfavorable prognosis. This set of genes includes a variety of molecules, such as cytokines, receptors, ligands, and other molecules with diverse functions. Conclusions: Our findings suggest that the set of 21 overexpressed genes in the High Vascularity group could potentially serve as prognostic markers for GB patients. These results highlight the importance of further investigating the relationship between the molecules such as cytokines or receptors underlying the vascularity in GB and its observation through MRI and developing targeted therapies for this aggressive disease.

Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension.

INTRODUCTION: Pulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. METHODS: A cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. RESULTS: A total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). CONCLUSION: In patients with PH, 75% have one, and 45% have two or more risk factors.

The Role of Defendant Gender and PTSD Diagnosis in a Battered Spouse Case.

A quarter of women and 11% of men report being survivors of intimate partner violence (IPV) during their lifetimes in the United States. Despite being victims themselves, people who kill their IPV abuser can still be subject to criminal proceedings. Given this complexity, the law has employed battered spouse syndrome (BSS) as a tool used in some jurisdictions to support a claim that an IPV survivor killed in self-defense. A defendant who is attempting to claim self-defense using BSS may introduce testimony of post-traumatic stress disorder (PTSD). However, a diagnosis of PTSD can pose problems in admission during litigation as the occurrence of a traumatic event is often what is being decided. The present study examined how college students, living on the U.S.-México border, perceive survivors-turned-defendants in a BSS mock trial. Specifically, we had each participant read a written trial transcript of a mock trial where gender of the defendant and clinical diagnosis of PTSD were manipulated. The current study hypothesized that jurors would be more lenient toward female defendants than male defendants (Hypothesis 1), jurors would be influenced by a PTSD diagnosis of the defendant (Hypothesis 2a-b), and female jurors would be more lenient than male jurors (Hypothesis 3). We also wanted to examine the impact of victim blaming, sexism, stigma of PTSD, and prior exposure to IPV on decision-making (Hypothesis 4a-d). Findings showed jurors were more lenient with female defendants than male defendants, however there was no effect of clinical diagnosis except on difficulty of decision. Implications of the role defendant gender has in decision-making is discussed.

Cost-Effectiveness of the Prenatal Detection of Congenital Heart Diseases: A Systematic Literature Review.

Background: Congenital heart disease is the most common congenital condition worldwide, with a prevalence of 80 cases per 10 000 live births. In addition to perinatal morbidity and mortality, it entails long-term consequences such as multiple surgeries, prolonged hospitalizations, lifelong cardiac follow-up, reduced quality of life, risk of heart failure, and premature mortality in adulthood. This significant health and economic burden on healthcare systems and families highlights the relevance of evaluating the cost-effectiveness of methods for early detection of this condition. Objective: To conduct a systematic literature review (SLR) to identify and analyze existing economic evaluations on prenatal detection of congenital heart diseases through ultrasound, focusing on the reported cost-effectiveness results and the methodological quality of the evaluated studies according to established criteria. Methods: An SLR of economic evaluations was conducted following PRISMA guidelines. A quantitative synthesis of key methodological components of each economic evaluation was performed. The incremental medical costs, effectiveness measures, and cost-effectiveness ratios reported in each study were compiled and compared. The methodological quality was assessed according to compliance with the 24 CHEERS criteria. Results: We found 785 articles, of which only 7 met all inclusion criteria. Most were cost-effectiveness analyses, with the most common outcome being number of cases detected. Screening with only 4-chamber views interpreted by general practitioners or cardiologists were dominant strategies compared with screening with 4-chamber plus outflow views interpreted by a general practitioner. Fetal echocardiography was most effective but most expensive. Screening with 4-chamber and outflow view, followed by referral to a specialist, were recommended as the least expensive strategy per defect detected. On average, articles met 17 of the 24 CHEERS criteria. Discussion: While recent cost-effectiveness analyses demonstrated improved methodological quality, there was a lack of homogeneity due to differences in comparators and population subgroups analyzed. Despite this heterogeneity, fetal ultrasonography screening was consistently identified as a cost-effective strategy, with its cost-effectiveness heavily influenced by the expertise of the interpreting physician. Conclusion: Most studies recommend implementing obstetric ultrasonography screening, without routine fetal echocardiography, for detecting congenital heart diseases.

Earlier detection of gestational diabetes impacts on medication requirements, neonatal and maternal outcomes.

AIM: Gestational diabetes (GD) is a global health concern with significant implications for maternal and neonatal outcomes. This study investigates the association between early GD (eGD) diagnosis (<24 weeks), pharmacotherapy requirements and adverse neonatal outcomes. MATERIALS AND METHODS: A cohort of 369 pregnant women underwent a 75-g oral glucose tolerance test. Maternal variables, pharmacotherapy prescriptions and neonatal outcomes were analysed employing t-tests, χ2 tests, and logistic regression. A p < .05 was considered significant. RESULTS: Early GD increased the odds of neonatal hypoglycaemia [odds ratio (OR): 18.57, p = .013] and respiratory distress syndrome (OR: 4.75, p = .034). Nutritional therapy prescription by an accredited nutritionist was the most common treatment in women diagnosed after 24 weeks, but those with eGD required more frequently specialized nutritional consulting + metformin to achieve glycaemic control (p = .027). eGD was associated with a higher requirement of nutritional therapy prescription + metformin (OR: 2.26, 95% confidence interval: 1.25-4.09, p = .007) and with maternal hyperglycaemia during the post-partum period at 2 h of the oral glucose tolerance test (OR: 1.03, 95% confidence interval: 1.02-1.13, p = .024). CONCLUSION: Timely diagnosis and personalized treatment of GD are desirable because an earlier presentation is related to a higher risk of adverse neonatal and maternal outcomes.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

Metagenomic analysis of microbial consortia native to the Amazon, Highlands, and Galapagos regions of Ecuador with potential for wastewater remediation.

Native microbial consortia have been proposed for biological wastewater treatment, but their diversity and function remain poorly understood. This study investigated three native microalgae-bacteria consortia collected from the Amazon, Highlands, and Galapagos regions of Ecuador to assess their metagenomes and wastewater remediation potential. The consortia were evaluated for 12 days under light (LC) and continuous dark conditions (CDC) to measure their capacity for nutrient and organic matter removal from synthetic wastewater (SWW). Overall, all three consortia demonstrated higher nutrient removal efficiencies under LC than CDC, with the Amazon and Galapagos consortia outperforming the Highlands consortium in nutrient removal capabilities. Despite differences in α- and ß-diversity, microbial species diversity within and between consortia did not directly correlate with their nutrient removal capabilities. However, all three consortia were enriched with core taxonomic groups associated with wastewater remediation activities. Our analyses further revealed higher abundances for nutrient removing microorganisms in the Amazon and Galapagos consortia compared with the Highland consortium. Finally, this study also uncovered the contribution of novel microbial groups that enhance wastewater bioremediation processes. These groups have not previously been reported as part of the core microbial groups commonly found in wastewater communities, thereby highlighting the potential of investigating microbial consortia isolated from ecosystems of megadiverse countries like Ecuador.

Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis.

Background: Immunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization. Methods: The immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy. Results: Our results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3+Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+Th1- and FOXP3+Treg cell differentiation. Conclusions: The results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo, as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high-quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis.

Working with companies that manufacture breastmilk substitutes: An EAACI position paper.

Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Safety and Efficacy of Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis.

Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21-0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12-2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01-11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1-2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.

Assessing SARS-CoV-2 Testing Adherence in a University Town: Recurrent Event Modeling Analysis.

BACKGROUND: Healthy Davis Together was a program launched in September 2020 in the city of Davis, California, to mitigate the spread of COVID-19 and facilitate the return to normalcy. The program involved multiple interventions, including free saliva-based asymptomatic testing, targeted communication campaigns, education efforts, and distribution of personal protective equipment, community partnerships, and investments in the local economy. OBJECTIVE: This study identified demographic characteristics of individuals that underwent testing and assessed adherence to testing over time in a community pandemic-response program launched in a college town in California, United States. METHODS: This study outlines overall testing engagement, identifies demographic characteristics of participants, and evaluates testing participation changes over 4 periods of the COVID-19 pandemic, distinguished by the dominant variants Delta and Omicron. Additionally, a recurrent model is employed to explore testing patterns based on the participants' frequency, timing, and demographic characteristics. RESULTS: A total of 770,165 tests were performed between November 18, 2020, and June 30, 2022, among 89,924 (41.1% of total population) residents of Yolo County, with significant participation from racially or ethnically diverse participants and across age groups. Most positive cases (6351 of total) and highest daily participation (895 per 100,000 population) were during the Omicron period. There were some gender and age-related differences in the pattern of recurrent COVID-19 testing. Men were slightly less likely (hazard ratio [HR] 0.969, 95% CI 0.943-0.996) to be retested and more likely (HR 1.104, 95% CI 1.075-1.134) to stop testing altogether than women. People aged between 20 and 34 years were less likely to be retested (HR 0.861, 95% CI 0.828-0.895) and more likely to stop testing altogether (HR 2.617, 95% CI 2.538-2.699). However, older age groups were less likely to stop testing, especially those aged between 65-74 years and 75-84 years, than those aged between 0 and 19 years. The likelihood of stopping testing was lower (HR 0.93, 95% CI 0.889-0.976) for the Asian group and higher for the Hispanic or Latino (HR 1.185, 95% CI 1.148-1.223) and Black or African American (HR 1.198, 95% CI 1.054-1.350) groups than the White group. CONCLUSIONS: The unique features of a pandemic response program that supported community-wide access to free asymptomatic testing provide a unique opportunity to evaluate adherence to testing recommendations and testing trends over time. Identification of individual and group-level factors associated with testing behaviors can provide insights for identifying potential areas of improvement in future testing initiatives.

Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer in women is 3-4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. METHODS: Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. RESULTS: In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. CONCLUSIONS: Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis.

Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses.

Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N2 adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses.

Hydrothermal processing of Sarcopeltis skottsbergii and study of the potential of its carrageenan for tissue engineering.

The red macroalga Sarcopeltis skottsbergii was subjected to hydrothermal processing to maximize the solubilization and recovery of carrageenan. Once isolated by ethanol precipitation, the carrageenan was further chemically (oligosaccharides composition), and structurally (TGA/DTG, DSC, HPSEC, FTIR-ATR, 1H NMR, SEM, etc.) characterized, as well as employed as source for the synthesis of hydrogels. The rheological properties of the carrageenan showed promising results as biopolymer for food applications due to the high molecular weight (500 kDa) presenting higher cell viability than 70 %. The evaluation of immune activation using ELISA test reflected a lower inflammatory response for concentrations of 0.025 % of carrageenan. Conversely, the cell viability of the synthesized hydrogels did not surpass 50 %. This work represents a considerable step forward to obtain a biopolymer from natural sources and a thorough study of their chemical, structural and biological properties.