•Three parent groups completed a semi-structured interview and validated survey tool.•Hispanic/Latinx parental groups had higher COVID-19 vaccine hesitancy.•Hypothetical parental willingness to ...vaccinate children was similar across groups.•Reasons for hesitancy fell most under Confidence, followed by Complacency.•Targeted COVID-19 vaccine education to different populations should be considered.
COVID-19 vaccinations are now recommended in the United States (U.S.) for children ≥ 6 months old. However, pediatric vaccination rates remain low, particularly in the Hispanic/Latinx population.
Using the 4C vaccine hesitancy framework (calculation, complacency, confidence, convenience), we examined parental attitudes in the emergency department (ED) towards COVID-19 vaccination, identified dimensions of parental vaccine hesitancy, and assessed parental willingness to have their child receive the COVID-19 vaccine.
As part of a larger multi-methods study examining influenza vaccine hesitancy, we conducted interviews that included questions about COVID-19 vaccine authorization for children. We used directed content analysis to extract qualitative themes from 3 groups of parents in the ED: Hispanic/Latinx Spanish speaking (HS), Hispanic/Latinx English speaking (HE), non-Hispanic/non-Latinx White English speaking (WE). Themes were triangulated with the Parent Attitudes about Childhood Vaccines (PACV) survey, where higher scores indicate increased vaccine hesitancy.
Factors influencing vaccine hesitancy were mapped to the 4C framework from 58 sets of interviews and PACVs. HE and HS parents, compared to WE parents, had less knowledge about COVID-19 and its vaccine, and more beliefs in COVID-19 vaccine myths. However, both HS and HE parent groups were more inclined to endorse COVID-19 vaccine effectiveness as a reason to have their children vaccinated. HS parents felt that COVID-19 increased their fear of illnesses in general and were worried about confusing COVID-19 with other infections. Median PACV scores of HS (Mdn = 20) and HE (Mdn = 20) parent groups were higher than of WE parents (Mdn = 10), but parental willingness to have their child receive COVID-19 vaccination was similar across groups.
Higher COVID-19 vaccine hesitancy among HS and HE parents compared to WE parents may be attributed to insufficient knowledge about COVID-19, its vaccine, along with COVID-19 vaccine myths. Efforts to provide targeted vaccine education to different populations is warranted.
Abstract
Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the ...cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA‐approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases.
Synopsis
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Deregulation of inflammasome activity contributes to hematopoietic alterations associated to chronic inflammatory diseases, including neutrophilia and anemia. Zebrafish models and human blood cells were used to identify the critical role of the NLRP1 inflammasome on the regulation of hematopoiesis and possible therapeutic targets for clinical intervention.
Erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis.
ZAKα/P38 kinase axis phosphorylated and promoted the assembly of NLRP1 in HSPCs which, in turn, regulates their erythroid‐myeloid lineage decision.
NLRP1 inflammasome in HSPCs was inhibited by LRRFIP1 and FLII, independently of DPP9.
The FDA/EMA‐approved drug Nilotinib inhibited NLRP1 inflammasome activation alleviating neutrophilia and promoting erythroid differentiation.
Twenty Pelibuey×Katahdin ewes (35±2.3 kg) were used to determine the effects of the consumption of standardized plant extract containing a mixture of quaternary benzophenanthridine alkaloids and ...protopine alkaloids (QBA+PA) on growth performance, dietary energetics, visceral mass, and ruminal epithelial health in heat-stressed ewes fed with a high-energy corn-based diet. The basal diet (13.9% crude protein and 2.09 Mcal of net energy NE of maintenance/kg of dry matter) contained 49.7% starch and 15.3% neutral detergent fiber. Source of QBA+PA was Sangrovit RS (SANG) which contains 3 g of quaternary benzophenathridine and protopine alkaloids per kg of product. Treatments consisted of a daily consumption of 0 or 0.5 g SANG/ewe. Ewes were grouped by weight and assigned to 10 pens (5 pens/treatment), with two ewes per pen. The experimental period lasted 70 days. The mean temperature humidity index during the course of this experiment was 81.7±1.0 (severe heat stress). There were no treatment effects on water intake. Dry matter intake was not affected (p = 0.70) by treatments, but the group fed SANG had a numerically (11.2%) higher gain in comparison to the control group, SANG improved gain efficiency (8.3%, p = 0.04), dietary NE (5.2%, p<0.01) and the observed-to-expected NE (5.9%, p<0.01). Supplemental SANG did not affect (p≥0.12) carcass characteristics, chemical composition of shoulder, and organ weights (g/kg empty body weight) of stomach complex, intestines, and heart/lung. Supplemental SANG decreased liver weight (10.3%, p = 0.02) and increased visceral fat (16.9%, p = 0.02). Rumen epithelium of ewes fed SANG had lower scores for cellular dropsical degeneration (2.08 vs 2.34, p = 0.02), parakeratosis (1.30 vs 1.82, p = 0.03) and neutrophil infiltration (2.08 vs 2.86, p = 0.05) than controls. It is concluded that SANG supplementation helped ameliorate the negative effects of severe heat on growth performance of feedlot ewes fed high-energy corn-based diets. Improvement in energetic efficiency may have been mediated, in part, by anti-inflammatory effects of supplemental SANG and corresponding enhancement of nutrient uptake.
This study describes a transversal (TV) ultrasound-guided erector spinae plane (ESP) block technique over the transverse process of T12. And evaluates the distribution of the dye and affected nerves ...branches compared to a longitudinal (LNG) approach over the transverse process of T12 in canine cadavers. Secondly, it also compares de anatomy and dimensions of the transverse processes of T12 with T9 and T5. For this double-masked, cadaveric experimental study, 12 adult Beagle cadavers were injected with 0.6 mL/kg of dye/contrast. Spread was evaluated by computed tomography (CT) and dissection.
Mean bodyweight was 9.76 (±0.59) kg. The TV and LNG approaches stained a median (range) of four (2–6) and three (1–6) medial branches of the dorsal rami of the spinal nerves, three (2–6) and three (2–5) lateral branches, and one (0−3) and one (0−4) ventral branches, respectively. Dye was detected in the epidural space in 55.6% and 66.7% of cases for the TV and LNG approaches, respectively (P=0.63). And in the ventral paravertebral compartment in 22.2% and lymphatics in 88.8% in both approaches. There were no statistical differences for the spread. The dorsolateral edge of the transverse process (TP) was not visible with CT at T12. The mean (±SD) length of the TP was significantly shorter at T12 3.34 (±0.22) mm, compared to T9 6.08 (±0.47) mm and T5 5.93 (±0.62) mm (P <0.001). This study showed similar distribution whether using a TV or LNG approach and differences in the anatomy and length of the T12 TP.
•The transversal (TV) and longitudinal (LNG) approaches had similar spread.•The TV approach had more ultrasound landmarks than the LNG approach.•TV and LNG groups had paravertebral, epidural, lymphatic, and sympathetic spread.•The transverse process at T12 is smaller and of different shape than in T9 and T5.
Background
Mortality from malignant cutaneous melanoma increased alarmingly during the second half of the 20th century in Spain and other European countries.
Objective
The aim was to analyse sex‐ and ...age‐specific trends in melanoma mortality in Spain in the period 1982–2016.
Methods
European age‐standardized melanoma mortality rates during the period 1982–2016 were calculated from mortality figures provided by the National Statistics Institute. Joinpoint regressions were used to identify significant points of change in trends and to compute average annual per cent change (AAPC). Age‐cohort‐period models were fitted to explore the effect of these variables on mortality.
Results
During the period 1982–2016, age‐standardized melanoma mortality rates increased in Spain from 0.90 to 1.80 deaths per 100 000 people in men and from 0.64 to 1.11 per 100 000 in women, rising noticeably from 1982 to 1995 in both sexes and in all age groups. From the mid‐90s different trends were observed depending on sex and age: there was a decrease in mortality in the population younger than 45 years (AAPC ‐2 in both sexes) and aged 45–64 years (AAPC ‐1 among men and ‐0.2 among women), but in the group over 64 years rates continued to increase (AAPC 1.7 and 0.2, respectively, for men and women). The mortality sex ratio decreased in the younger population but increased in older individuals. A cohort effect was observed with lower mortality in the cohorts born after 1943 in men and 1956 in women. There was also a period effect with decreased mortality rates at the beginning of the 1990s.
Conclusions
Melanoma mortality rates in Spain increased during the last decades of the 20th century; however, later they stabilized in women and began to decrease in younger cohorts and middle‐aged men. Promotion of primary and secondary prevention measures should continue, with particular emphasis on males over 65 years.
Edible composite coatings based on hydroxypropyl methylcellulose (HPMC), lipid components (beeswax and shellac), and food preservatives with antifungal properties were evaluated in vivo on clementine ...mandarins cv. Clemenules, hybrid mandarins cv. Ortanique, and oranges cv. Valencia. Their curative and preventive activity against citrus postharvest green (GM) and blue molds (BM), caused by Penicillium digitatum (PD) or Penicillium italicum (PI), respectively, were determined. Fruits were artificially inoculated before or after the application of the coatings and incubated up to 7 days at 20 °C. Selected food preservatives included mineral salts, organic acid salts, parabens, and 2-deoxy-d-glucose. Inoculated but uncoated fruits were used as controls. For curative activity, HPMC-lipid edible composite coatings containing sodium benzoate (SB) were most effective in reducing the incidence and severity of GM on clementine mandarins cv. Clemenules (86 and 90%, respectively). On this cultivar, the reduction in GM incidence by the SB-based coating was twice that of potassium sorbate (PS)-based coating. On mandarins cv. Ortanique, PS- and SB-based coatings reduced the incidence of GM and BM by more than 40 and 21%, respectively. However, the HPMC-lipid coating containing a mixture of PS and sodium propionate (PS + SP) exhibited a synergistic effect in the reduction of the incidence of GM (78%) and BM (67%). Coatings with parabens modestly reduced disease incidence and severity. On oranges cv. Valencia, coatings with food preservatives better controlled BM than GM. Coatings containing SB + PS and SB + SP reduced the incidence and severity of BM by 85% and 95%, respectively. PS- and SB- based coatings controlled GM more effectively than coatings formulated with other food preservatives. In every cultivar, fruit coated before inoculation did not show any incidence or severity reduction of both GM and BM (preventive activity). In every test, the antifungal action of the coatings was fungistatic rather than fungicidal.
Hereditary tyrosinemia type I (HT1) is a rare disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH) in the tyrosine catabolic pathway, resulting mainly in hepatic alterations due to ...accumulation of the toxic metabolites fumarylacetoacetate, maleylacetoacetate and succinylacetone. We have characterized using minigenes four splicing mutations affecting exonic or intronic nucleotides of the FAH gene identified in two HT1 patients. Two of the mutations are novel, c.82‐1G>A and c.913G>C and the other two have been previously associated with a splicing defect (c.836A>G and c.1062+5G>A). All mutations were confirmed to affect splicing in minigenes, resulting in exon skipping or activation of a cryptic splice site. We have analyzed the effect of different compounds known to modulate splicing (valproic acid, phenyl butyrate, M344, EIPA, and resveratrol) and the overexpression of splice factors of the SR protein family on the transcriptional profile of the mutant minigenes. For the c.836A>G mutation, a partial recovery of the correctly spliced transcript was observed. These results confirm the relevance of performing functional studies for mutations potentially affecting the splicing process and open the possibility of supplementary therapeutic approaches to diseases caused by splicing defects.
Macrophages take center stage in the tumor microenvironment, a niche composed of extracellular matrix and a heterogeneous group of cells, including immune ones. They can evolve during tumor ...progression and acquire Tumor-Associated Macrophage (TAMs) phenotype. The release of cytokines by tumor and stromal cells, influence the secretion of cytokines by TAMs, which can guarantee tumor progression and influence the response to therapy. Among all factors able to recruit and polarize macrophages, we focused our attention on Bcl-xL, a multifaceted member of the Bcl-2 family, whose expression is deregulated in melanoma. It acts not only as a canonical pro-survival and anti-apoptotic protein, but also as a promoter of tumor progression.
Human melanoma cells silencing or overexpressing Bcl-xL protein, THP-1 monocytic cells and monocyte-derived macrophages were used in this study. Protein array and specific neutralizing antibodies were used to analyze cytokines and chemokines secreted by melanoma cells. qRT-PCR, ELISA and Western Blot analyses were used to evaluate macrophage polarization markers and protein expression levels. Transwell chambers were used to evaluate migration of THP-1 and monocyte-derived macrophages. Mouse and zebrafish models were used to evaluate the ability of melanoma cells to recruit and polarize macrophages in vivo.
We demonstrated that melanoma cells overexpressing Bcl-xL recruit macrophages at the tumor site and induce a M2 phenotype. In addition, we identified that interleukin-8 and interleukin-1β cytokines are involved in macrophage polarization, and the chemokine CCL5/RANTES in the macrophages recruitment at the tumor site. We also found that all these Bcl-xL-induced factors are regulated in a NF-kB dependent manner in human and zebrafish melanoma models.
Our findings confirmed the pro-tumoral function of Bcl-xL in melanoma through its effects on macrophage phenotype.
Reducing feeding costs in suckler beef herds to improve economic returns could have detrimental impacts on fertility. This study sought to determine whether maternal nutrient restriction during early ...pregnancy affects interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells during the peri-implantation period in two beef cattle breeds. Relationships were also examined between subnutrition and pregnancy failure defined according to ISG fold changes on Days 18 and 21 and to plasma pregnancy specific protein B (PSPB) concentrations on Day 28 post-artificial insemination (AI). Pirenaica or Parda de Montaña dams were assigned to a control (n = 23) or subnutrition (n = 30) group, receiving 100% or 65% of their estimated nutritional requirements from Day 1 to 82 post-AI, respectively. Treatment did not affect ISG expression or fertility. According to ISG fold changes (chi-square P = .023) or PSPB levels (chi-square P = .04) recorded in the subnutrition group, late embryo loss was more likely than in controls. Positive correlation was detected between Day 28 PSPB concentrations and both Day 18 MX1, MX2 and ISG15 expression, and Day 21 OAS1 expression. OAS1 and MX1 fold changes were found to be the best variables to discriminate pregnancy status. Our findings indicate that maternal nutrient restriction during the first third of pregnancy does not impair embryo signalling yet may increase the risk of pregnancy failure.
•Maternal subnutrition in suckler beef cattle does not impair conceptus signalling.•Nutrient restriction in early pregnancy may increase the risk of pregnancy failure.•OAS1 and MX1 fold changes were the best variables to predict pregnancy status.
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