Management of cow’s milk protein allergy (CMPA) can vary depending on the experience and area of expertise of the clinician responsible for the patient’s follow-up, which may or may not align with ...the recently published literature. To analyze the perspectives of Spanish pediatricians on this topic, a survey was conducted. The survey aimed to determine the current opinions and attitudes of 222 primary care and hospital pediatricians toward CMPA prevention and nutritional management. Participating pediatricians completed the questionnaire, providing insights into their daily clinical practices, including access to testing, attitudes with respect to various aspects of CMPA diagnosis, prevention, oral food challenges, and treatment. The findings revealed that pediatricians generally agree on the use of extensively hydrolyzed formulas (eHFs) to prevent CMPA in high-risk atopic children, despite limited evidence supporting the widespread use of this practice. However, consensus was lacking regarding the utility of formulas with prebiotics and probiotics for expediting tolerance development. In most cases, pediatricians preferred eHFs for the nutritional management of CMPA, followed by hydrolyzed rice formulas (HRFs), with amino-acid-based formulas (AAFs) being the third option. Certain issues remained controversial among pediatricians, such as prevention methods, symptom assessment, and the role of probiotics. These variations in management approaches reflect the influence of clinician experience and area of expertise, underscoring the need for standardized guidelines in this field.
p38γ and p38δ (p38γ/p38δ) regulate inflammation, in part by controlling tumor progression locus 2 (TPL2) expression in myeloid cells. Here, we demonstrate that TPL2 protein levels are dramatically ...reduced in p38γ/p38δ-deficient (p38γ/δ
) cells and tissues without affecting
messenger ribonucleic acid (mRNA) expression. We show that p38γ/p38δ posttranscriptionally regulates the TPL2 amount at two different levels. p38γ/p38δ interacts with the TPL2/A20 Binding Inhibitor of NF-κB2 (ABIN2)/Nuclear Factor κB1p105 (NF-κB1p105) complex, increasing TPL2 protein stability. Additionally, p38γ/p38δ regulates
mRNA translation by modulating the repressor function of
3' Untranslated region (UTR) mediated by its association with aconitase-1 (ACO1). ACO1 overexpression in wild-type cells increases the translational repression induced by
3'UTR and severely decreases TPL2 protein levels. p38δ binds to ACO1, and p38δ expression in p38γ/δ
cells fully restores TPL2 protein to wild-type levels by reducing the translational repression of
mRNA. This study reveals a unique mechanism of posttranscriptional regulation of TPL2 expression, which given its central role in innate immune response, likely has great relevance in physiopathology.
Livestock grazing is a major economic activity worldwide. Cattle frequently graze and congregate in watercourses and riparian areas because of the availability of water, shade and the quality and ...variety of forage, thereby altering the ecological condition of stream ecosystems. We have explored the effects of cattle intrusion on the environmental conditions and fish assemblages of four neotropical prairie streams from Argentina’s Pampas region. At each stream, both ungrazed and grazed conditions were surveyed. Water quality, habitat structure, riparian vegetation and fish assemblages were sampled. Significant detrimental changes were observed in environmental conditions of grazed sites in contrast to ungrazed sites. Fish assemblage structure and function were also significantly influenced by the environmental conditions imposed by cattle intrusion. Our results reveal the magnitude and direction of environmental changes imposed by cattle intrusion in prairie streams and highlight several key aspects of fish assemblages and populations that change accordingly. Relevant aspects for conservation and management purposes of these fragile ecosystems, such as protection of riparian vegetation condition and the control of cattle access and social engagement, are discussed.
The COVID-19 pandemic has highlighted the need for innovative approaches to its diagnosis. Here we present CoVradar, a novel and simple colorimetric method that combines nucleic acid analysis with ...dynamic chemical labeling (DCL) technology and the Spin-Tube device to detect SARS-CoV-2 RNA in saliva samples. The assay includes a fragmentation step to increase the number of RNA templates for analysis, using abasic peptide nucleic acid probes (DGL probes) immobilized to nylon membranes in a specific dot pattern to capture RNA fragments. Duplexes are formed by labeling complementary RNA fragments with biotinylated SMART bases, which act as templates for DCL. Signals are generated by recognizing biotin with streptavidin alkaline phosphatase and incubating with a chromogenic substrate to produce a blue precipitate. CoVradar results are analysed by CoVreader, a smartphone-based image processing system that can display and interpret the blotch pattern. CoVradar and CoVreader provide a unique molecular assay capable of detecting SARS-CoV-2 viral RNA without the need for extraction, preamplification, or pre-labeling steps, offering advantages in terms of time (∼3 h/test), cost (∼€1/test manufacturing cost) and simplicity (does not require large equipment). This solution is also promising for developing assays for other infectious diseases.
Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This ...large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.
Atherinopsidae are widespread freshwater and shallow marine fish with singular economic importance. Morphological, genetical and life cycles differences between marine and estuarine populations were ...already reported in this family, suggesting ongoing speciation. Also, coexistence and interbreeding between closely related species were documented. The aim of this study was to infer boundaries among: (A) Odontesthes bonariensis and O. argentinensis at species level, and intermediate morphs; (B) the population of O. argentinensis of Mar Chiquita Lagoon and its marine conspecifics. To achieve this, we integrated, meristic, Geometrics Morphometrics and DNA Barcode approaches. Four groups were discriminated and subsequently characterized according to their morphological traits, shape and meristic characters. No shared haplotypes between O. bonariensis and O. argentinensis were found. Significative-meristic and body shape differences between the Mar Chiquita and marine individuals of O. argentinensis were found, suggesting they behave as well differentiated populations, or even incipient ecological species. The fact that the Odontesthes morphotypes shared haplotypes with both, O. argentinensis and O. bonariensis, but also possess meristic and morphometric distinctive traits open new questions related to the origin of this morphogroup.
Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with ...acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke.
The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.
Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 95% CI 0·55–7·85; p=0·28), eight (44%) in the high-dose group (1·89 0·52–6·96; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 0·72–6·85; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.
Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.
Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.
Elimination of gluten-containing cereals and consumption of ultra-processed gluten-free foods might cause an unbalanced diet, deficient in fiber and rich in sugar and fat, circumstances that may ...predispose celiac children to chronic constipation.
to evaluate if counseling with a registered dietitian (RD) was capable of improving eating and bowel habits in a celiac pediatric population.
Dietetic, lipid profile and stool modifications were analyzed, comparing baseline assessments with those twelve months after receiving heathy eating and nutrition education sessions. At both time points, 3-day food records, a bowel habit record and a lipid panel were conducted. Calculated relative intake of macro- and micro-nutrients were compared with current recommendations by the European Food Safety Authority (EFSA). Student's paired
-test, McNemar test, Mandasky test and Pearson correlation tests were used.
Seventy-two subjects (58.3% girls) with a mean (standard deviation (SD)) age of 10.2 (3.4) years were included. Baseline diets were imbalanced in macronutrient composition. Significant improvements were observed in their compliance with dietary reference values (DRVs), where 50% of the subjects met fat requirements after the education and 67% and 49% with those of carbohydrates and fiber, respectively (
< 0.001). Celiac children decreased red meat and ultra-processed foods consumption (
< 0.001) and increased fruits and vegetables intake (
< 0.001), leading to a reduction in saturated fat (
< 0.001) and sugar intake (
< 0.001). Furthermore, 92% of the patients achieved a normal bowel habit, including absence of hard stools in 80% of children constipated at baseline (
< 0.001).
RD-led nutrition education is able to improve eating patterns in children with celiac disease (CD).
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