Weather and climate change are constant and ever-changing processes that affect allergy and asthma. The purpose of this report is to provide information since the last climate change review with a ...focus on asthmatic disease. PubMed and Internet searches for topics included climate and weather change, air pollution, particulates, greenhouse gasses, traffic, insect habitat, and mitigation in addition to references contributed by the individual authors. Changes in patterns of outdoor aeroallergens caused by increasing temperatures and amounts of carbon dioxide in the atmosphere are major factors linked to increased duration of pollen seasons, increased pollen production, and possibly increased allergenicity of pollen. Indoor air pollution threats anticipated from climate changes include microbial and mold growth secondary to flooding, resulting in displacement of persons and need for respiratory protection of exposed workers. Air pollution from indoor burning of mosquito repellants is a potential anticipatory result of an increase in habitat regions. Air pollution from fossil fuel burning and traffic-related emissions can alter respiratory defense mechanisms and work synergistically with specific allergens to enhance immunogenicity to worsen asthma in susceptible subjects. Community efforts can significantly reduce air pollution, thereby reducing greenhouse gas emission and improving air quality. The allergist's approach to weather pattern changes should be integrated and anticipatory to protect at-risk patients.
Kabuki syndrome is a Mendelian disorder of the epigenetic machinery characterized by typical dysmorphic features, intellectual disability, and postnatal growth deficiency. Pathogenic variants in the ...genes encoding the chromatin modifiers KMT2D and KDM6A are responsible for Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), respectively. In addition, 11 cases of KS1 caused by mosaic variants in KMT2D have been reported in the literature. Some of these individuals display milder craniofacial and growth phenotypes, and most do not have congenital heart defects. We report the case of an infant with severe hypoplastic left heart syndrome with mitral atresia and aortic atresia (HLHS MA‐AA), pulmonary vein stenosis, and atypical facies with a somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*) identified on trio exome sequencing of peripheral blood and present in 11.2% of sequencing reads. KS was confirmed with EpiSign, a diagnostic genome‐wide DNA methylation platform used to identify epigenetic signatures. This case suggests that use of this newly available clinical test can guide the interpretation of low‐level mosaic variants identified through sequencing and suggests a new lower limit of mosaicism in whole blood required for a diagnosis of KS.
Peak inspiratory flow (PIF) has been proposed as a measure to assess a patient's ability to use dry powder inhalers (DPIs). However, robust quality criteria to determine a repeatability limit for ...measuring PIF are lacking.
What are the repeatability limits for measuring PIF? What is the relationship between PIF measured using the In-Check DIAL device at Diskus (GlaxoSmithKline; PIF
) and HandiHaler (Boehringer Ingelheim; PIF
) resistances?
Data from a randomized, controlled, phase 3 trial (study 0149; see Clinical Trial Registration data) were used to define repeatability limits for PIF. In addition, a model to characterize the relationship between PIF measured with the In-Check DIAL device at PIF
and PIF
was defined using data from two randomized, controlled, phase 3 trials (studies 0128 and 0149).
In study 0128, the mean values (SD) for PIF at zero resistance and PIF
were 84.6 (33.4) and 57.3 (26.1) L/min, respectively. In study 0149, the mean values (SD) for PIF
and PIF
were 42.4 (11.2) and 29.0 (8.3) L/min, respectively. At the mean level, the mean difference between measurement attempts for PIF
and PIF
was small, < 5 and < 3 L/min, respectively. The repeatability limit was determined as 10 and 5 L/min for PIF
and PIF
, respectively. Modeling the relationship between PIF
and PIF
, after controlling for significant covariates, demonstrated that a PIF
value of 60 L/min was approximately equivalent to PIF
of 40 L/min.
This analysis demonstrated that the two highest values of PIF using the In-Check DIAL device among three inspiratory efforts, met the repeatability limit. Altogether, these data provide guidance for measuring PIF against the simulated resistance of a specific DPI in clinical practice and research studies.
ClinicalTrials.gov; Nos.: NCT02518139 (study 0128) and NCT03095456 (study 0149); URL: www.clinicaltrials.gov.
Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory ...flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®).
This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV
) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI.
We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV
, 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV
from baseline; however, the difference versus tiotropium was not significant (least squares LS mean difference standard error, 17.0 22.4 mL, P=0.4461). In a prespecified analysis of patients with FEV
< 50% predicted, revefenacin produced an LS mean difference (95% confidence interval CI), 49.1 (6.3-91.9) mL in trough FEV
and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV
in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV
< 50% predicted populations.
Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV
in patients with FEV
< 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).
The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes—CAMK2A, CAMK2B, CAMK2G, and CAMK2D—of which the first three ...have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in humans. We identified eight individuals harboring heterozygous variants in CAMK2D who display symptoms of intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms. Together, we describe a cohort of individuals with neurodevelopmental disorders and cardiac anomalies, harboring pathogenic variants in CAMK2D, confirming an important role for the CAMK2D isozyme in both heart and brain function.
CAMK2 disorder is a relatively new disorder where three of the four CAMK2s (CAMK2A, B, and G) are shown to cause neurodevelopmental disorders. In this paper we describe a cohort of eight individuals with neurodevelopmental disorders and cardiac abnormalities, having CAMK2D variants, proving all CAMK2s are important for normal development.
Gravid mammals are more prone to listeriosis than their nongravid counterparts. However, many features of the disease in gravid animals are not well defined. We determined, in mice, that increased ...susceptibility to lethal infection following oral inoculation begins surprisingly early in pregnancy and extends through embryonic development. Pregnancy did not demonstrably increase the spread of listeriae from the intestine to the liver and spleen in the initial 96 h period post inoculation. Consequently, it appeared that gravid animals were competent to contain an enteric infection, but in those instances where escape did occur, a lethal outcome was more likely. Interestingly, colonic colonization level and prevalence, measured 96 h post inoculation, was significantly higher in gravid individuals. In terms of human risk factors for listeriosis, our results suggest that the window of listeriosis susceptibility afforded by pregnancy may be open longer than previously appreciated. Our results also suggest that while gravid animals are competent to contain an enteric infection, enteric carriage rate may be more of a factor in defining disease incidence than previously considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Peak Inspiratory Flows Barnes, Chris N.; Mahler, Donald A.; Ohar, Jill A. ...
Chest,
October 2020, 2020-10-00, Letnik:
158, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Peak inspiratory flow (PIF) has been proposed as a measure to assess a patient’s ability to use dry powder inhalers (DPIs). However, robust quality criteria to determine a repeatability limit for ...measuring PIF are lacking.
What are the repeatability limits for measuring PIF? What is the relationship between PIF measured using the In-Check DIAL device at Diskus (GlaxoSmithKline; PIFD) and HandiHaler (Boehringer Ingelheim; PIFHH) resistances?
Data from a randomized, controlled, phase 3 trial (study 0149; see Clinical Trial Registration data) were used to define repeatability limits for PIF. In addition, a model to characterize the relationship between PIF measured with the In-Check DIAL device at PIFD and PIFHH was defined using data from two randomized, controlled, phase 3 trials (studies 0128 and 0149).
In study 0128, the mean values (SD) for PIF at zero resistance and PIFHH were 84.6 (33.4) and 57.3 (26.1) L/min, respectively. In study 0149, the mean values (SD) for PIFD and PIFHH were 42.4 (11.2) and 29.0 (8.3) L/min, respectively. At the mean level, the mean difference between measurement attempts for PIFD and PIFHH was small, < 5 and < 3 L/min, respectively. The repeatability limit was determined as 10 and 5 L/min for PIFD and PIFHH, respectively. Modeling the relationship between PIFD and PIFHH, after controlling for significant covariates, demonstrated that a PIFD value of 60 L/min was approximately equivalent to PIFHH of 40 L/min.
This analysis demonstrated that the two highest values of PIF using the In-Check DIAL device among three inspiratory efforts, met the repeatability limit. Altogether, these data provide guidance for measuring PIF against the simulated resistance of a specific DPI in clinical practice and research studies.
ClinicalTrials.gov; Nos.: NCT02518139 (study 0128) and NCT03095456 (study 0149); URL: www.clinicaltrials.gov.
The goal of this study is to understand if there are any variations regarding student engagement and course outcomes based on the course format. A new course format was introduced in fall of 2006 ...that involves a hybrid approach (large lecture with small recitations) with a higher level of student enrollment than traditional research methods courses. During the same time frame, the discipline maintained its traditional research methods courses as well. A survey was administered to all students enrolled in research methods regardless of course format in fall 2006 and spring 2007. Student responses are discussed, including information concerning the preparation, design, cost and benefits of offering a hybrid research methods course format.
This study investigates the distribution and heart levels of glucose regulated protein (GRP) 78 during normal development and in response to hypoglycemia in the mouse. Results demonstrate that GRP78 ...is strongly expressed with in the heart, neural tube, gut endoderm, somites, and surface ectoderm of mouse embryos during early organogenesis, and GRP78 staining remains prominent in the heart from gestational days 9.5 through 13.5. Cardiac myocytes are the primary site of GRP78 expression within the heart. GRP78 levels are highest in the heart during early organogenesis and levels decrease significantly by the fetal period. GRP78 expression is increased after 24 h of hypoglycemia in the early organogenesis-stage heart. Considering the tissue specific pattern of GRP expression and changes during development of the heart, GRPs may play significant roles in the normal differentiation and development of cardiac tissue. GRP induction may also be involved in hypoglycemia-induced cardiac dysmorphogenesis.
Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this ...population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise.
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