Abstract Background Clonal mast cell disorders are known to occur in a subset of patients with systemic reactions to Hymenoptera stings. This observation has prompted the question as to whether ...clonal mast cell disorders also occur in patients with idiopathic anaphylaxis (IA). Objective We sought to determine the prevalence of clonal mast cell disorders among patients with IA, criteria to identify those patients who require a bone marrow biopsy and whether the pathogenesis of IA involves a hyper-responsive mast cell compartment. Methods We prospectively enrolled patients with IA (≥3 episodes/yr) and who then underwent a medical evaluation that included a serum tryptase determination, allele-specific quantitative polymerase chain reaction (ASqPCR) for KIT D816V and a bone marrow examination. Mast cells were cultured from peripheral blood CD34+ cells and examined for releasibility following FcεRI aggregation. Results Clonal mast cell disease was diagnosed in 14% of patients referred with IA. ASqPCR for the KIT D816V mutation was a useful adjunct in helping identify those with systemic mastocytosis (SM) but not monoclonal mast cell activation syndrome (MMAS). A modified overall clonal prediction model was developed using clinical findings, a serum tryptase determination and ASqPCR. There was no evidence of a hyper-responsive mast cell phenotype in patients with IA. Conclusion Patients with clonal mast cell disease may present as idiopathic anaphylaxis. Distinct clinical and laboratory features may be used to select those patients more likely to have an underlying clonal mast cell disorder (MMAS or SM) and thus candidates for a bone marrow biopsy.
Aim: Children with cutaneous or systemic mastocytosis may experience severe manifestations of mast cell mediator release including anaphylaxis. The perceived risk for adverse vaccine reactions ...creates concern among parents and pediatricians regarding modification of the routine vaccine schedule for safety. Materials and Methods: Using the National Institutes of Health (NIH) Biomedical Translational Research Information System and Clinical Research Information System, we conducted a retrospective chart review of 94 children less than or equal to18 years of age, evaluated at NIH with mastocytosis. Based on the recommended childhood immunization schedule, we estimated that these 94 patients received approximately 2,136 vaccinations. Post vaccination reactions were determined as expected or unexpected according to the centers for disease control (CDC) parameters for vaccine-associated events. Results: Eighty-four patients (89.4%) had no reports of moderate-severe post-vaccination reactions. Eleven reactions after vaccination were reported in 10 of 94 patients (10.6%), of which four patients had unexpected reactions (4.3%). Unexpected reactions included facial swelling, flushing and exacerbation of skin lesions which are not reported as possible vaccine reactions by the CDC. One patient was treated for anaphylaxis 2 hours post-varicella vaccine administration. Five patients with a history of anaphylaxis and a mean tryptase level of 115 ng/mL did not report vaccine-induced reactions. Conclusion: Children with mastocytosis in this study did not experience a higher rate of adverse vaccine reactions compared to the general population. Anaphylaxis to other causes was not a risk factor for an untoward vaccine response. In patients that experience a severe post-vaccination reaction such as anaphylaxis, a modified schedule with single vaccine administration is a safer approach. Keywords: Pediatrics, mastocytosis, vaccines
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
The diagnostic criteria for paediatric mastocytosis are largely based on adult studies and bone marrow findings are not well described in children. We evaluated use of the World Health ...Organization (WHO) criteria for the diagnosis of systemic disease in paediatric mastocytosis. In addition, we identified unique clinico‐histopathological features within the biopsies. One hundred and thirteen children with paediatric mastocytosis were evaluated at the National Institutes of Health between 1986 and 2013. Complete bone marrow evaluations were performed in 50 cases. Seven children had repeat procedures. Bone marrows were analysed by histopathology, flow cytometry and for KIT D816V. Bone marrow biopsies displayed mild atypical haematopoietic maturation, increased haematogones and hypocellularity in a sub‐set of patients with urticaria pigmentosa, diffuse cutaneous mastocytosis and indolent systemic mastocytosis. Hypocellularity was most pronounced in those with urticaria pigmentosa. Haematogones were highest, on average, in patients with diffuse cutaneous mastocytosis or mastocytomas. There was no evidence of peripheral blood cytopenias, myelodysplastic syndrome, myeloproliferative neoplasm or leukaemia within this cohort. The WHO criteria are applicable for the diagnosis of systemic mastocytosis in paediatrics. Although unsuspected bone marrow findings typically seen in myeloproliferative disorders are frequent in paediatric mastocytosis, patients within this study remained clinically stable without progression to a more aggressive variant.
Abstract
Objective
Belonging is often considered a buffer against the physical and emotional consequences of discrimination and racial climate stress Youth Soc. 48(5):649–72, 2016. However, recent ...research suggests that feelings of belonging toward an institution can be detrimental when an individual feels discriminated against by the same institution to which one feels a sense of connection J Behav Med. 44(4):571–8, 2021. Therefore, the present study aimed to investigate the moderating role of institutional belonging in the relationship between racial climate stress and health, as indexed by allostatic load (AL), a multi-system indicator of physiological dysregulation.
Methods
In a sample of Black and White college students (
N
= 150; White = 82; Black = 68), self-reported racial climate stress, institutional belonging, and various demographic variables were collected. An AL composite was also collected, comprised of six biological measures of the SAM system, HPA axis, cardiovascular system, and metabolic system. Multiple regression analyses were conducted to explore the relationships between these variables.
Results
Results demonstrated no main effect of racial climate stress on AL but did show a significant interaction between racial climate stress and belonging, such that the positive relationship between racial climate stress and AL was significant only for those who also felt high levels of institutional belonging (
β
int
= .05,
p
= .006, 95% CI = 0.01 – 0.08).
Conclusions
Feeling a sense of belonging may have negative physiological consequences for those who experience racial climate stress in a college setting.
Legitimate opioid prescriptions have been identified as a risk factor for opioid misuse in pediatric patients. In 2014, Pennsylvania legislation expanded a prescription drug monitoring program (PDMP) ...to curb inappropriate controlled substance prescriptions. The authors' objective was to describe recent opioid prescribing trends at a large, pediatric health system situated in a region with one of the highest opioid-related death rates in the United States and examine the impact of the PDMP on prescribing trends.
Quasi-experimental assessment of trends of opioid e-prescriptions, from 2012 to 2017. Multivariable Poisson segmented regression examined the effect of the PDMP. Period prevalence comparison of opioid e-prescriptions across the care continuum in 2016.
There were 62,661 opioid e-prescriptions identified during the study period. Combination opioid/non-opioid prescriptions decreased, while oxycodone prescriptions increased. Seasonal variation was evident. Of 110,884 inpatient encounters, multivariable regression demonstrated lower odds of an opioid being prescribed at discharge per month of the study period (p < 0.001) and a significant interaction between passage of the PDMP legislation and time (p = 0.03). Black patients had lower odds of receiving an opioid at discharge compared to white patients. Inpatients had significantly greater odds of receiving an opioid compared to emergency department (Prevalence Odds Ratio 7.1 95% confidence interval: 6.9-7.3; p < 0.001) and outpatient (398.9 355.5-447.5; p < 0.001) encounters.
In a large pediatric health system, oxycodone has emerged as the most commonly prescribed opioid in recent years. Early evidence indicates that a state-run drug monitoring program is associated with reduced opioid prescribing. Additional study is necessary to examine the relationship between opioid prescriptions and race.
Sustainability Science: Toward a Synthesis Clark, William C; Harley, Alicia G
Annual review of environment and resources,
10/2020, Letnik:
45, Številka:
1
Journal Article
Recenzirano
Odprti dostop
This review synthesizes diverse approaches that researchers have brought to bear on the challenge of sustainable development. We construct an integrated framework highlighting the union set of ...elements and relationships that those approaches have shown to be useful in explaining nature-society interactions in multiple contexts. Compelling evidence has accumulated that those interactions should be viewed as a globally interconnected, complex adaptive system in which heterogeneity, nonlinearity, and innovation play formative roles. The long-term evolution of that system cannot be predicted but can be understood and partially guided through dynamic interventions. Research has identified six capacities necessary to support such interventions in guiding development pathways toward sustainability. These are capacities to (
a
) measure sustainable development, (
b
) promote equity, (
c
) adapt to shocks and surprises, (
d
) transform the system into more sustainable development pathways, (
e
) link knowledge with action, and (
f
) devise governance arrangements that allow people to work together in exercising the other capacities.
Synonymous rare codons are considered to be sub-optimal for gene expression because they are translated more slowly than common codons. Yet surprisingly, many protein coding sequences include large ...clusters of synonymous rare codons. Rare codons at the 5' terminus of coding sequences have been shown to increase translational efficiency. Although a general functional role for synonymous rare codons farther within coding sequences has not yet been established, several recent reports have identified rare-to-common synonymous codon substitutions that impair folding of the encoded protein. Here we test the hypothesis that although the usage frequencies of synonymous codons change from organism to organism, codon rarity will be conserved at specific positions in a set of homologous coding sequences, for example to tune translation rate without altering a protein sequence. Such conservation of rarity-rather than specific codon identity-could coordinate co-translational folding of the encoded protein. We demonstrate that many rare codon cluster positions are indeed conserved within homologous coding sequences across diverse eukaryotic, bacterial, and archaeal species, suggesting they result from positive selection and have a functional role. Most conserved rare codon clusters occur within rather than between conserved protein domains, challenging the view that their primary function is to facilitate co-translational folding after synthesis of an autonomous structural unit. Instead, many conserved rare codon clusters separate smaller protein structural motifs within structural domains. These smaller motifs typically fold faster than an entire domain, on a time scale more consistent with translation rate modulation by synonymous codon usage. While proteins with conserved rare codon clusters are structurally and functionally diverse, they are enriched in functions associated with organism growth and development, suggesting an important role for synonymous codon usage in organism physiology. The identification of conserved rare codon clusters advances our understanding of distinct, functional roles for otherwise synonymous codons and enables experimental testing of the impact of synonymous codon usage on the production of functional proteins.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts.
A convenience sample of 193 ...employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100-1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); and, across workplace settings.
Working hours were mostly spent sedentary (77.0%, 95%CI: 76.3, 77.6), with approximately half of this time accumulated in prolonged bouts of 20 minutes or more. There were significant (p<0.05) differences in all outcomes between workdays and non-work days, and, on workdays, between work- versus non-work hours. Results consistently showed "work" was more sedentary and had less light-intensity activity, than "non-work". The period immediately after work appeared important for MVPA. There were significant (p<0.05) differences in all sedentary and activity outcomes occurring during work hours across the workplace settings. Call-centre workers were generally the most sedentary and least physically active at work; customer service workers were typically the least sedentary and the most active at work.
The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.
The initial movement of herders and livestock into the eastern steppe is of great interest, as this region has long been home to pastoralist groups. Due to a paucity of faunal remains, however, it ...has been difficult to discern the timing of the adoption of domesticated ruminants and horses into the region, though recent research on ancient dairying has started to shed new light on this history. Here we present proteomic evidence for shifts in dairy consumption in the Altai Mountains, drawing on evidence from sites dating from the Early Bronze to the Late Iron Age. We compare these finds with evidence for the rise of social complexity in western Mongolia, as reflected in material remains signaling population growth, the establishment of structured cemeteries, and the erection of large monuments. Our results suggest that the subsistence basis for the development of complex societies began at the dawn of the Bronze Age, with the adoption of ruminant livestock. Investments in pastoralism intensified over time, enabling a food production system that sustained growing populations. While pronounced social changes and monumental constructions occurred in tandem with the first evidence for horse dairying, ~1350 cal BCE, these shifts were fueled by a long-term economic dependence on ruminant livestock. Therefore, the spread into the Mongolian Altai of herds, and then horses, resulted in immediate dietary changes, with subsequent social and demographic transformations occurring later.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the changes in ICU admissions, ventilatory support, length of stay, and cost for patients with bronchiolitis in the United States.
Retrospective cross-sectional study of the Pediatric ...Health Information Systems database. All patients age <2 years admitted with bronchiolitis and discharged between January 1, 2010 and December 31, 2019, were included. Outcomes included proportions of annual ICU admissions, invasive mechanical ventilation (IMV), noninvasive ventilation (NIV), and cost.
Of 203 859 admissions for bronchiolitis, 39 442 (19.3%) were admitted to an ICU, 6751 (3.3%) received IMV, and 9983 (4.9%) received NIV. ICU admissions for bronchiolitis doubled from 11.7% in 2010 to 24.5% in 2019 (
< .001 for trend), whereas ICU admissions for all children in Pediatric Health Information Systems <2 years of age increased from 16.0% to 21.1% during the same period (
< .001 for trend). Use of NIV increased sevenfold from 1.2% in 2010 to 9.5% in 2019 (
< .001 for trend). Use of IMV did not significantly change (3.3% in 2010 to 2.8% in 2019,
= .414 for trend). In mixed-effects multivariable logistic regression, discharge year was a significant predictor of NIV (odds ratio: 1.24; 95% confidence interval CI: 1.23-1.24) and ICU admission (odds ratio: 1.09; 95% CI: 1.09-1.09) but not IMV (odds ratio: 1.00; 95% CI: 1.00-1.00).
The proportions of children with bronchiolitis admitted to an ICU and receiving NIV have substantially increased, whereas the proportion receiving IMV is unchanged over the past decade. Further study is needed to better understand the factors underlying these temporal patterns.
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