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1.
Heliyon ; 10(11): e31175, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38832259

RESUMEN

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.

2.
Pediatr Allergy Immunol ; 35(5): e14142, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38753422

RESUMEN

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.


Asunto(s)
Leche Humana , Humanos , Lactante , Leche Humana/inmunología , Recién Nacido , Fórmulas Infantiles/economía , Sustitutos de la Leche , Europa (Continente) , Femenino , Lactancia Materna , Industria de Alimentos , Fenómenos Fisiológicos Nutricionales del Lactante
3.
Front Immunol ; 15: 1385101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725998

RESUMEN

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.


Asunto(s)
Antígenos de Plantas , Proteínas Portadoras , Hipersensibilidad a los Alimentos , Inmunidad Innata , Humanos , Hipersensibilidad a los Alimentos/inmunología , Femenino , Antígenos de Plantas/inmunología , Proteínas Portadoras/inmunología , Masculino , Adulto , Citocinas/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Proteínas de Plantas/inmunología , Activación de Linfocitos/inmunología , Adulto Joven , Persona de Mediana Edad
4.
Diabetes Obes Metab ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38699781

RESUMEN

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.

5.
Allergy ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700063

RESUMEN

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.

6.
Environ Microbiol Rep ; 16(3): e13272, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692845

RESUMEN

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.


Asunto(s)
Bacterias , Metagenómica , Consorcios Microbianos , Aguas Residuales , Ecuador , Aguas Residuales/microbiología , Consorcios Microbianos/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Microalgas/clasificación , Microalgas/metabolismo , Purificación del Agua , Biodegradación Ambiental , Metagenoma
8.
Contact Dermatitis ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38812248

RESUMEN

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.

9.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38697283

RESUMEN

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.

10.
Liver Cancer ; 13(3): 227-237, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38756146

RESUMEN

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.

11.
J Health Econ Outcomes Res ; 11(1): 141-148, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800495

RESUMEN

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.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38561566

RESUMEN

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.

13.
Cancers (Basel) ; 16(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38610938

RESUMEN

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.

14.
JMIR Public Health Surveill ; 10: e48784, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38631033

RESUMEN

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.


Asunto(s)
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Femenino , Estados Unidos , Anciano , Adulto Joven , Adulto , Prueba de COVID-19 , Pandemias , Universidades
16.
Glob Implement Res Appl ; 4(1): 102-115, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38566954

RESUMEN

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38579942

RESUMEN

BACKGROUND: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function (GOF) IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. OBJECTIVE: We studied 7 relatives with autoimmune/inflammatory and lymphoproliferative manifestations to identify the immunologic disturbances and the genetic cause of their disease. METHODS: We analyzed biopsy results and performed whole-exome sequencing and immunologic studies. RESULTS: Disease onset occurred at a mean age of 25.2 years (range, 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, 4 had confirmed IG4-related disease (IgG4-RD), and 5 developed B-cell malignancies: lymphoma in 4 and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening coronavirus disease 2019 pneumonia, of whom 1 had autoantibodies neutralizing IFN-α. The recently described IKZF1 GOF p.R183H variant was found in the 5 affected relatives tested and in a 6-year-old asymptomatic girl. Immunologic analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, effector memory CD4 T cells that have regained surface expression of CD45RA and CD28-CD57+ CD4+ and CD8+ T cells, TH2, and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in 3 patients. CONCLUSIONS: Heterozygosity for GOF IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD, and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunologic data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

18.
Viruses ; 16(4)2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38675991

RESUMEN

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.


Asunto(s)
COVID-19 , Predisposición Genética a la Enfermedad , Genotipo , Interferón gamma , SARS-CoV-2 , Femenino , Humanos , Masculino , Alelos , COVID-19/genética , COVID-19/virología , Síndrome de Liberación de Citoquinas/genética , Frecuencia de los Genes , Interferón gamma/genética , Polimorfismo de Nucleótido Simple , SARS-CoV-2/patogenicidad , Factor de Necrosis Tumoral alfa/genética
19.
Front Public Health ; 12: 1349609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680934

RESUMEN

Introduction: The rise in global temperatures due to climate change has escalated the frequency and intensity of wildfires worldwide. Beyond their direct impact on physical health, these wildfires can significantly impact mental health. Conventional mental health studies predominantly rely on surveys, often constrained by limited sample sizes, high costs, and time constraints. As a result, there is an increasing interest in accessing social media data to study the effects of wildfires on mental health. Methods: In this study, we focused on Twitter users affected by the California Tubbs Fire in 2017 to extract data signals related to emotional well-being and mental health. Our analysis aimed to investigate tweets posted during the Tubbs Fire disaster to gain deeper insights into their impact on individuals. Data were collected from October 8 to October 31, 2017, encompassing the peak activity period. Various analytical methods were employed to explore word usage, sentiment, temporal patterns of word occurrence, and emerging topics associated with the unfolding crisis. Results: The findings show increased user engagement on wildfire-related Tweets, particularly during nighttime and early morning, especially at the onset of wildfire incidents. Subsequent exploration of emotional categories using Linguistic Inquiry and Word Count (LIWC) revealed a substantial presence of negative emotions at 43.0%, juxtaposed with simultaneous positivity in 23.1% of tweets. This dual emotional expression suggests a nuanced and complex landscape, unveiling concerns and community support within conversations. Stress concerns were notably expressed in 36.3% of the tweets. The main discussion topics were air quality, emotional exhaustion, and criticism of the president's response to the wildfire emergency. Discussion: Social media data, particularly the data collected from Twitter during wildfires, provides an opportunity to evaluate the psychological impact on affected communities immediately. This data can be used by public health authorities to launch targeted media campaigns in areas and hours where users are more active. Such campaigns can raise awareness about mental health during disasters and connect individuals with relevant resources. The effectiveness of these campaigns can be enhanced by tailoring outreach efforts based on prevalent issues highlighted by users. This ensures that individuals receive prompt support and mitigates the psychological impacts of wildfire disasters.


Asunto(s)
Salud Mental , Medios de Comunicación Sociales , Incendios Forestales , Medios de Comunicación Sociales/estadística & datos numéricos , Humanos , California , Emociones
20.
Int J Biol Macromol ; 266(Pt 2): 131456, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38588844

RESUMEN

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.


Asunto(s)
Carragenina , Hidrogeles , Rhodophyta , Ingeniería de Tejidos , Carragenina/química , Ingeniería de Tejidos/métodos , Hidrogeles/química , Animales , Supervivencia Celular/efectos de los fármacos , Ratones , Reología , Humanos , Materiales Biocompatibles/química , Peso Molecular
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