RESUMO

The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

Assuntos

RESUMO

The aim of this study was to investigate the independent and joint associations of low cardiorespiratory fitness and lower-limb muscle strength with cardiometabolic risk in older adults. A total of 360 community-dwelling older adults aged 60-80 years participated in this cross-sectional study. Cardiometabolic risk was based on the diagnosis of Metabolic Syndrome and poor Ideal Cardiovascular Health according to the American Heart Association guidelines. Cardiorespiratory fitness and lower-limb muscle strength were estimated using the six-minute walk and the 30-second chair stand tests, respectively. Participants in the 20th percentile were defined as having low cardiorespiratory fitness and lower-limb muscle strength. Poisson's regression was used to determine the prevalence ratio (PR) and 95% confidence intervals (CI) of Metabolic Syndrome and poor Ideal Cardiovascular Health. Participants with low cardiorespiratory fitness alone and combined with low lower-limb muscle strength were similarly associated with a higher risk for Metabolic Syndrome (PR 1.27, 95% CI 1.09-1.48, and PR 1.32, 95% CI 1.10-1.58, respectively), and poor Ideal Cardiovascular Health (PR 1.76, 95% CI 1.25-2.47, and PR 1.65, 95% CI 1.19-2.28, respectively). Low lower-limb muscle strength alone was not associated with a higher risk for either Metabolic Syndrome or poor Ideal Cardiovascular Health (PR 1.23, 95% CI 0.81-1.87, and PR 1.11, 95% CI 0.89-1.37, respectively). Low cardiorespiratory fitness alone or combined with low lower-limb muscle strength, but not low lower-limb muscle strength alone, was associated with a higher cardiometabolic risk in older adults. The assessment of physical fitness may be a "window of opportunity" to identify youngest-old adults with a high cardiovascular disease risk.

Assuntos

RESUMO

AbstractDetermining whether and how evolution is predictable is an important goal, particularly as anthropogenic disturbances lead to novel species interactions that could modify selective pressures. Here, we use a multigeneration field experiment with brown anole lizards (Anolis sagrei) to test hypotheses about the predictability of evolution. We manipulated the presence/absence of predators and competitors of A. sagrei across 16 islands in the Bahamas that had preexisting brown anole populations. Before the experiment and again after roughly five generations, we measured traits related to locomotor performance and habitat use by brown anoles and used double-digest restriction enzyme-associated DNA sequencing to estimate genome-wide changes in allele frequencies. Although previous work showed that predators and competitors had characteristic effects on brown anole behavior, diet, and population sizes, we found that evolutionary change at both phenotypic and genomic levels was difficult to forecast. Phenotypic changes were contingent on sex and habitat use, whereas genetic change was unpredictable and not measurably correlated with phenotypic changes, experimental treatments, or other environmental factors. Our work shows how differences in ecological context can alter evolutionary outcomes over short timescales and underscores the difficulty of forecasting evolutionary responses to multispecies interactions in natural conditions, even in a well-studied system with ample supporting ecological information.

Assuntos

RESUMO

OBJECTIVE: To describe alcohol use, alcohol-related harm, and alcohol-related problems preoperatively and up to 8 years following metabolic and bariatric surgery (MBS) in adolescents. BACKGROUND: Risk for alcohol use and alcohol use disorders (AUD) increases post-Roux-en-Y gastric bypass and vertical sleeve gastrectomy in adults. However, data are lacking in adolescents who undergo MBS. METHODS: This study includes 217 adolescents (aged 13-19 y) enrolled in a 5-center prospective cohort study who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy (2007-2011) and reported alcohol use preoperatively and annually postoperatively for up to 8 years. Time to elevated Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score, alcohol-related harm, and alcohol-related problems were analyzed with Kaplan-Meier estimates of cumulative incidence. RESULTS: Preoperatively, the median age was 17 years; the median body mass index was 51 kg/m 2 . Alcohol use frequency and average quantity of drinks per drinking day increased postoperatively (2% consumed alcohol 2-4 times/month 6 months versus 24% 8 years postoperatively, P <0.001; 2% consumed≥3 drinks per drinking day 6 months versus 35% 8 years postoperatively, P <0.001). Cumulative incidence of postoperative onset elevated AUDIT-C score, alcohol-related harm, and alcohol-related problems at year 8 were 45% (95% CI:37-53), 43% (95% CI:36-51), and 47% (95% CI:40-55), respectively. CONCLUSIONS: Nearly half of those who underwent MBS as adolescents screened positively for AUD, symptoms of alcohol-related harm, or alcohol-related problems 8 years post-MBS, highlighting the risk for alcohol use and AUD after MBS in adolescents. AUD evaluation and treatment should be integrated into routine long-term care for adolescents undergoing MBS.

Assuntos

RESUMO

Total mercury (THg) concentrations were measured in muscle and liver of two placental viviparous sharks, the Pacific sharpnose shark (Rhizoprionodon longurio) and the brown smooth-hound (Mustelus henlei); as well as in the muscle, liver, and yolk of the yolk-sac viviparous speckled guitarfish (Pseudobatos glaucostigmus) in Baja California Sur. The aim was to determine which factors could be involved in maternal transfer and resultant maternal and embryonic THg concentration. Higher THg concentrations were found in pregnant females compared to embryos paired tissues. THg concentrations of embryo tissues decreased with total length (TL), except for the muscle of the Pacific sharpnose shark. THg concentrations of embryo muscle was positively related to THg concentration in the muscle of pregnant females. Embryos TL, muscle THg concentration of pregnant females, percentage of THg concentration in embryos, along with the reproductive strategy are relevant factors required to improve our understanding of THg concentration in embryo tissues.

Assuntos

RESUMO

Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in acute lymphoblastic leukemia (ALL). The TACL2014-001 phase I trial of the mTOR inhibitor temsirolimus in combination with cyclophosphamide and etoposide was performed in children and adolescents with relapsed/refractory ALL. Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily on days 1-5. The starting dose of temsirolimus was 7.5 mg/m2 (DL1) with escalation to 10 mg/m2 (DL2), 15 mg/m2 (DL3), and 25 mg/m2 (DL4). PI3K/mTOR pathway inhibition was measured by phosphoflow cytometry analysis of peripheral blood specimens from treated patients. Sixteen heavily-pretreated patients were enrolled with 15 evaluable for toxicity. One dose-limiting toxicity of grade 4 pleural and pericardial effusions occurred in a patient treated at DL3. Additional dose-limiting toxicities were not seen in the DL3 expansion or DL4 cohort. Grade 3/4 non-hematologic toxicities occurring in three or more patients included febrile neutropenia, elevated alanine aminotransferase, hypokalemia, mucositis, and tumor lysis syndrome and occurred across all doses. Response and complete were observed at all dose levels with a 47% overall response rate and 27% complete response rate. Pharmacodynamic correlative studies demonstrated dose-dependent inhibition of PI3K/mTOR pathway phosphoproteins in all studied patients. Temsirolimus at doses up to 25 mg/m2 with cyclophosphamide and etoposide had an acceptable safety profile in children with relapsed/refractory ALL. Pharmacodynamic mTOR target inhibition was achieved and appeared to correlate with temsirolimus dose. Future testing of next-generation PI3K/mTOR pathway inhibitors with chemotherapy may be warranted to increase response rates in children with relapsed/refractory ALL.

Assuntos

RESUMO

Mercury (Hg) is a well-known toxicant in wildlife and humans. High total Hg concentrations ([THg]) have been reported in central California harbor seals Phoca vitulina richardii. We evaluated the effects of presence/absence of early natal coat (lanugo), year (2012 to 2017), sex, stranding location, and trophic ecology (ẟ13C and ẟ15N values) on hair [THg] along coastal central California. Also examined were [THg] effects on growth rates of pups in rehabilitation and probability of release (e.g., successful rehabilitation). The [THg] ranged from 0.46-81.98 mg kg-1 dw, and ẟ15N and ẟ13C ranged from 13.6-21.5‰, and -17.2 to -13.0‰, respectively. Stranding location, year, and presence of lanugo coat were important factors explaining variation in [THg]. Seals from Sonoma and San Mateo County had higher [THg] than other locations. Seals with full or partial lanugo coat had lower [THg]. Seals from 2016 and 2017 had higher [THg] than those from 2015. Hair [THg] exceeded lower and upper toxicological thresholds (>20 mg kg-1 by year (5.88% to 23.53%); >30 mg kg-1 (0% to 12.31%)) with a pronounced increase from 2015 to 2016. Pups in 2017 had significantly higher odds ratio of [THg] above 20 mg kg-1 than pups of 2015, and pups in 2016 had significantly higher odds ratio than those from 2013 and 2015 (similar when using 30 mg kg-1). Pups in Sonoma County had the highest odds ratio for [THg] in lanugo above 20 mg kg-1. ẟ15N values were higher in 2015-2017, particularly relative to 2014, probably associated with the El Niño event. The [THg] was not a good predictor for probability of release and mass-specific growth rates in captivity. Further investigation of temporal trends of [THg] in harbor seals is warranted given the relatively high percentage of samples exceeding threshold values, particularly in the most recent sampling years.

Assuntos

RESUMO

Identifying the particular guilds of herbivore arthropods that affect the production of crops is key to developing sustainable pest-management strategies; however, there is incomplete information about the identity of herbivore arthropods that could potentially damage the production of both highland and lowland quinoa landraces grown in Chile. By both reviewing the literature and conducting field collections across a large latitudinal gradient, we generated an updated list of 43 herbivore arthropods associated with quinoa production in Chile. In general, most species are polyphagous feeders, and only seven are specialists. The number and identity of species varied in relation with the latitude, such that four distinctive assemblages of herbivores were identified, each containing 32, 27, 34, and 22 species between latitudes 18-26, 26-32, 32-40, and 40-44° S, respectively. The most northern production area (18-26° S) is affected by nine unique species, including the major quinoa pest Eurysacca quinoae Povolný (Lepidoptera: Gelechiidae). Similarly, the central area (32-40° S) contains four unique species, including Eurysacca media Povolný (Lepidoptera: Gelechiidae) and Orthotylus flavosparsus (Sahlberg) (Hemiptera: Miridae). The particular species assemblages described here will help further development of local pest-management practices.

RESUMO

Helicoverpa armigera (Hübner) is one of the most important agricultural pests in the world. This historically Old World species was first reported in Brazil in 2013 and has since spread throughout much of South America and into the Caribbean. Throughout North America, H. armigera surveys are ongoing to detect any incursions. Each trap is capable of capturing hundreds of native Helicoverpa zea (Boddie). The two species cannot be separated without genitalic dissection or molecular methods. A ddPCR assay is currently used to screen large trap samples, but this equipment is relatively uncommon and expensive. Here, we optimized a newly designed assay for accurate and repeatable detection of H. armigera in bulk samples across both ddPCR and less costly, and more common, real-time PCR methods. Improvements over previously designed assays were sought through multiple means. Our results suggest bulk real-time PCR assays can be improved through changes in DNA extraction and purification, so that real-time PCR can be substituted for ddPCR in screening projects. While ddPCR remains a more sensitive method for detection of H. armigera in bulk samples, the improvements in assay design, DNA extraction, and purification presented here also enhance assay performance over previous protocols.

RESUMO

Nitrogen stable isotopes ratios (δ15 N) were determined for selected tissues (muscle, liver, blood and yolk) of pregnant females and their embryos of a placental viviparous species, the Pacific sharpnose shark (Rhizoprionodon longurio), and a yolk-sac viviparous species, the speckled guitarfish (Pseudobatos glaucostigmus). The R. longurio embryo tissues were 15 N enriched compared to the same tissues in the pregnant female, using the difference in δ15 N (Δδ15 N) between embryo and adult. Mean Δδ15 N was 2.17‰ in muscle, 4.39‰ in liver and 0.80‰ in blood. For P. glaucostigmus, embryo liver tissue was significantly 15 N enriched in comparison with liver of the pregnant female (Δδ15 N mean = 1.22‰), whereas embryo muscle was 15 N depleted relative to the muscle of the pregnant female (Δδ15 N mean = -1.22‰). Both species presented a significant positive linear relationship between Δδ15 N and embryo total length (LT ). The results indicated that embryos have different Δδ15 N depending on their reproductive strategy, tissue type analysed and embryo LT .

Assuntos