•FINLAY-FR-2 conjugate vaccine is safe and immunogenic in children 3-18 years old.•The third dose with FINLAY-FR-1A (dimer receptor binding domain vaccine) increases the immune response.•The ...heterologous three-dose schedule elicited specific T-cell response.•This vaccination elicits neutralizing antibodies vs the Delta and Omicron variants of concern.•Immune response in children is non-inferior to young adults.
To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines.
A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results.
Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval CI 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron.
The heterologous scheme was safe and immunogenic in children 3-18 y/o.
https://rpcec.sld.cu/trials/RPCEC00000374
To assess the proportion of myeloid-derived suppressor cells (MDSCs), their expression of arginase-1 and programmed cell death ligand 1 (PD-L1) and their relationship with the clinical phenotype of ...patients with idiopathic inflammatory myopathies (IIMs).
We recruited 37 IIM adult patients and 10 healthy donors in Mexico City. We evaluated their clinical features, the proportion of MDSCs and their expression of PD-L1 and arginase-1 by flow cytometry. Polymorphonuclear (PMN)-MDSCs were defined as CD33dim, CD11b+ and CD66b+ while monocytic (M)-MDSCs were CD33+, CD11b+, HLA-DR- and CD14+. Serum cytokines were analysed with a multiplex assay. We compared the quantitative variables with the Kruskal-Wallis and Mann-Whitney U tests and assessed correlations with Spearman's ρ.
Most patients had dermatomyositis n = 30 (81.0%). IIM patients had a peripheral expansion of PMN-MDSCs and M-MDSCs with an enhanced expression of arginase-1 and PD-L1. Patients with active disease had a decreased percentage {median 1.75% interquartile range (IQR) 0.31-5.50 vs 10.71 3.16-15.58, P = 0.011} of M-MDSCs and a higher absolute number of PD-L1+ M-MDSCs median 23.21 cells/mm3 (IQR 11.16-148.9) vs 5.95 (4.66-102.7), P = 0.046 with increased expression of PD-L1 median 3136 arbitrary units (IQR 2258-4992) vs 1961 (1885-2335), P = 0.038. PD-L1 expression in PMN-MDSCs correlated with the visual analogue scale of pulmonary disease activity (r = 0.34, P = 0.040) and damage (r = 0.36, P = 0.031), serum IL-5 (r = 0.55, P = 0.003), IL-6 (r = 0.46, P = 0.003), IL-8 (r = 0.53, P = 0.018), IL-10 (r = 0.48, P = 0.005) and GM-CSF (r = 0.48, P = 0.012). M-MDSCs negatively correlated with the skeletal Myositis Intention to Treat Index (r = -0.34, P = 0.038) and positively with IL-6 (r = 0.40, P = 0.045).
MDSCs expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.
Introducción: Los síntomas de la esfera gastrointestinal superior son conocidos como síntomas dispépticos, pudiendo ocurrir en periodos postprandiales. Objetivo: Analizar los efectos de levosulpiride ...sobre la motilidad gástrica en pacientes con dispepsia no investigada con molestia postprandial que acuden al servicio de gastroenterología del Hospital Universitario de Caracas periodo enero – marzo 2023. Pacientes y Método: Se realizó un estudio tipo descriptivo, prospectivo, de corte transversal. 30 pacientes cumplieron los criterios de inclusión. Se determinó la capacidad gástrica y la sintomatología antes y después del uso del levosulpiride a través de la prueba de tolerancia al agua. La población fue conformada por pacientes que acudieron al servicio de gastroenterología del Hospital Universitario de Caracas, con síntomas de saciedad temprana y/o llenura postprandial además de otros síntomas dispépticos. Se calculó media y se compararon mediante T de Student variables cuantitativas Gaussianas, prueba de Mann Whitney para las no Gaussianas y Chi cuadrado para variables cualitativas, considerando significativo un valor de p ≤ 0.05. Resultados: La edad promedio fue 43,93 ± 15,45 años, con un rango etario de 22 a 78 años, predominó el género femenino (56,7%). Al comparar el síntoma referido antes y después de la administración de levosulpiride, no hubo diferencias estadísticamente significativas. Al comparar el volumen de agua ingerido antes y después de la administración de levosulpiride, hubo diferencias estadísticamente significativas (1057,4 cc vs 1485,7 cc, p=0.00001). Conclusión: Con el levosulpiride los pacientes no refieren síntomas a volúmenes basales, pudiéndose aumentar el volumen ingerido significativamente antes de referir síntomas. Además constituye una opción terapéutica útil en el manejo de los pacientes con dispepsia no investigada contribuyendo a mejorar la calidad de vida del paciente.
Latinx populations are underrepresented in DNA-based research, and risk not benefiting from research if underrepresentation continues. Latinx populations are heterogenous; reflect complex social, ...migration, and colonial histories; and form strong global diasporas. We conducted a global study using a survey tool (Amazon’s Mechanical Turk portal) to ascertain willingness to participate in genetic research by Latin America birth-residency concordance. Participants in the global study identified as Latinx (
n
=250) were classified as the following: (1) born/live outside of Latin America and the Caribbean (LAC), (2) born within/live outside LAC, and (3) born/live within LAC. Latinx were similarly likely to indicated they would participate DNA-based research as their non-Latinx counterparts (52.8% vs. 56.2%, respectively). Latinx born and living in LAC were significantly more willing to participate in DNA-based research than Latinx born and living outside of LAC (OR: 2.5; 95% CI: 1.3, 4.9,
p
<.01). Latinx indicating they would participate in genetic research were more likely to trust researchers (<.05), believe genetic research could lead to better understanding of disease (<.05), and that genetic research could lead to new treatments (
p
<.05) when compared with Latinx not interested in participating in genetic research. In summary, significant variation exists in genetic research interest among Latinx based on where they were born and live, suggesting that this context itself independently influences decisions about participation. Cultivating and investing in a research ecosystem that addresses, values, and respects Latinx priorities, circumstances, and researchers would likely increase research participation and, even more importantly, potentially impact the inequitable health disparities disproportionately represented in Latinx communities.
Background
Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not ...been thoroughly demonstrated.
Objective
To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19.
Design
We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial.
Participants
We recruited 116 hospitalized patients with severe COVID-19 in Mexico.
Interventions
Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment.
Main Measures
The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients.
Key Results
Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93,
P
= 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88,
P
= 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A.
Conclusions
Colchicine is safe but not effective in the treatment of severe COVID-19.
Trial Registration
ClinicalTrials.gov Identifier: NCT04367168.
Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric ...nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition.
We collected faeces and blood samples to study the microbiome, the serum metabolome and circulating cytokines and miRNAs from a cohort of 105 fibromyalgia patients and 54 age- and environment-matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from faeces samples. UPLC-MS metabolomics and custom multiplex cytokine and miRNA analysis (FirePlex™ technology) were used to examine sera samples. Finally, we combined the different data types to search for potential biomarkers.
We found that the diversity of bacteria is reduced in fibromyalgia patients. The abundance of the Bifidobacterium and Eubacterium genera (bacteria participating in the metabolism of neurotransmitters in the host) in these patients was significantly reduced. The serum metabolome analysis revealed altered levels of glutamate and serine, suggesting changes in neurotransmitter metabolism. The combined serum metabolomics and gut microbiome datasets showed a certain degree of correlation, reflecting the effect of the microbiome on metabolic activity. We also examined the microbiome and serum metabolites, cytokines and miRNAs as potential sources of molecular biomarkers of fibromyalgia.
Our results show that the microbiome analysis provides more significant biomarkers than the other techniques employed in the work. Gut microbiome analysis combined with serum metabolomics can shed new light onto the pathogenesis of fibromyalgia. We provide a list of bacteria whose abundance changes in this disease and propose several molecules as potential biomarkers that can be used to evaluate the current diagnostic criteria.
Antimicrobial peptides (AMPs) are gaining interest as potential therapeutic agents. Peptides derived from bovine lactoferricin B (LfcinB) have been reported to exhibit antimicrobial activity, and the ...LfcinB RRWQWR sequence is the smallest known motif that exhibits antibacterial and cytotoxic activity. Our goal was to examine the effect of multicopy arrangements of the RRWQWR motif, on its antibacterial activity against healthcare-associated infections (HCAIs). Linear and branched peptides containing the RRWQWR motif were generated using solid phase peptide synthesis-Fmoc/tBu methodology, purified, and characterized using reverse phase-high performance liquid chromatography and matrix-assisted laser desorption/ionization time of flight mass spectrometry. For each peptide, the antibacterial activity against Staphylococcus aureus (ATCC 25923 and 33591 strains) and Klebsiella pneumoniae (ATCC 13883 and 700603 strains) was assessed by measuring the minimum inhibitory and the minimum bactericidal concentrations, in the exponential phase. Cells were observed by scanning electron microscopy, and the hemolytic activity of the peptides was assessed. The overall results demonstrate that, compared to linear analogues, polyvalent presentation of the RRWQWR motif enhances its antibacterial activity against both Gram-negative and Gram-positive bacteria even on resistant strain.
Phosphate metabolism was studied to determine whether polyphosphate (polyP) pools play a role in the enhanced resistance against Cd
2+
and metal-removal capacity of Cd
2+
-preadapted (CdPA)
...Methanosarcina acetivorans
. Polyphosphate kinase (PPK), exopolyphosphatase (PPX) and phosphate transporter transcript levels and their activities increased in CdPA cells compared to control (Cnt) cells. K
+
inhibited recombinant Ma-PPK and activated Ma-PPX, whereas divalent cations activated both enzymes. Metal-binding polyP and thiol-containing molecule contents, Cd
2+
-removal, and biofilm synthesis were significantly higher in CdPA cells >Cnt cells
plus
a single addition of Cd
2+
>Cnt cells. Also, CdPA cells showed a higher number of cadmium, sulfur, and phosphorus enriched-acidocalcisomes than control cells. Biochemical and physiological phenotype exhibited by CdPA cells returned to that of Cnt cells when cultured without Cd
2+
. Furthermore, no differences in the sequenced genomes upstream and downstream of the genes involved in Cd
2+
resistance were found between CdPA and Cnt cells, suggesting phenotype loss rather than genome mutations induced by chronic Cd
2+
-exposure. Instead, a metabolic adaptation induced by Cd
2+
stress was apparent. The dynamic ability of
M. acetivorans
to change its metabolism, depending on the environmental conditions, may be advantageous to remove cadmium in nature and biodigesters.
Purpose
To search for regulated proteins in response to green tea (–)‐epigallocatechin‐3‐gallate (EGCG) in A549 lung cancer cells.
Experimental design
2DE and ESI/multistage MS (ESI‐MS/MS) were ...performed to identify modulated proteins in A549 cells treated with EGCG. Cell migration was evaluated by transwell assays. RNA interference was used to silence the hepatoma‐derived growth factor (HDGF). Caspase‐3, caspase‐9, and HDGF were immunodetected by Western blot assays. Flow cytometry was used for detection of mitochondrial membrane potential and apoptosis.
Results
We found that HDGF expression was threefold suppressed by EGCG treatment. Downregulation of HDGF by EGCG was confirmed using anti‐HDGF antibodies in three lung cancer cell lines. EGCG treatment and HDGF abrogation by RNA interference resulted in a decreased migration of A549 cells. In addition, EGCG induced a marked synergistic effect with cisplatin in cell death. Consistently, an enhanced cytotoxicity in HDGF‐silenced cells was also found. Cell death was associated to increased apoptosis, disruption of the mitochondrial membrane potential, and activation of caspase‐3 and caspase‐9.
Conclusion and clinical relevance
Our data suggest for the first time that abrogation of HDGF by EGCG enhances cisplatin‐induced apoptosis and sensitize A549 cells to chemotherapy. Therefore, we propose that decreasing the HDGF levels by using EGCG may represent a novel strategy in lung cancer therapy.
The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and ...treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years.
An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%.
Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios.
This GIO guideline provides evidence-based guidance for health care providers treating patients.
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