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Delayed Diagnosis of Critical Congenital Heart Defects: Trends and Associated Factors

Delayed diagnosis of critical congenital heart defects (CCHDs) is associated with increased morbidity and mortality.

Despite increasing prenatal diagnosis rates, delayed diagnosis of CCHDs continues to occur, with rates highest among isolated cases and those delivered at nontertiary care hospitals. Better understanding of delayed diagnosis could help to improve screening efforts. (Read the full article)




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Cardiovascular Risk Factors in Adolescents Born Preterm

Adolescents and adults born early preterm have higher blood pressure and altered glucose metabolism compared with their term born peers. Evidence of an atherogenic lipid profile is inconsistent. Whether these risks apply to those born less preterm is not known.

In adolescence, girls have higher blood pressure and boys a more atherogenic lipid profile than their term born peers. Overall, our results are consistent with a dose-response relationship between shorter length of gestation and increasing levels of cardiovascular risk factors. (Read the full article)




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Age-Based Risk Factors for Pediatric ATV-Related Fatalities

Younger age has been identified as an independent risk factor for all-terrain vehicle (ATV)-related injuries. Since the mid-1980s, one-third of ATV-related deaths have involved children younger than 18 years of age.

Using national data, we found both similarities and differences between pediatric age groups in the contribution of known risk factors to ATV-related deaths. The observed differences suggest the importance of targeting injury prevention approaches to specific age ranges. (Read the full article)




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Risk Factors for Exclusive E-Cigarette Use and Dual E-Cigarette Use and Tobacco Use in Adolescents

There is a debate about whether e-cigarettes will benefit public health. However, there is little knowledge about how e-cigarette users and dual users (those using both e-cigarettes and tobacco cigarettes) differ from other adolescents on a range of variables.

Teenagers who only used e-cigarettes were intermediate in levels of risk and protective factors between nonusers and those who used both cigarettes and e-cigarettes. This raises a question about whether e-cigarettes recruit low-risk youth to tobacco product use. (Read the full article)




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Cardiovascular Risk Factors in Children After Repeat Doses of Antenatal Glucocorticoids: An RCT

Administration of repeat doses of antenatal glucocorticoids to women at risk for preterm birth after an initial course reduces neonatal morbidity, without affecting rates of neurologic disability in early childhood. However, data on long-term effects on cardiometabolic health are limited.

Exposure to repeat doses of antenatal betamethasone did not increase cardiovascular risk factors at early school age. Clinicians wishing to use repeat antenatal glucocorticoids can be reassured that the risk of future cardiometabolic disease from this therapy is low. (Read the full article)




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Factors Associated With Meaningful Use Incentives in Children's Hospitals

Meaningful use (MU) incentive payments have been developed to encourage adoption and use of electronic health records (EHRs). Several studies have revealed children’s hospitals have unique barriers to the use of EHRs but were relatively early adopters of information technology.

Although a minority of children’s hospitals have succeeded with MU incentives, freestanding children’s hospitals are significantly more likely to succeed. Improvement of EHRs for pediatric use should focus on information exchange, quality reporting, and MU relevance to pediatrics. (Read the full article)




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Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring

Vesicoureteral reflux is recognized as an important risk factor for recurrent urinary tract infection and renal scarring. Less is known about the contribution of other risk factors to these outcomes.

This study found that information about vesicoureteral reflux and bladder and bowel dysfunction can be used to identify children at low, medium, and high risk of recurrent urinary tract infection, information that clinicians could use to select children for specific preventive therapies. (Read the full article)




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Prevalence of and Risk Factors for Intracranial Abnormalities in Unprovoked Seizures

Weak recommendations exist to guide emergent neuroimaging decisions in children with first, unprovoked seizures. The prevalence of and risk factors associated with clinically relevant abnormalities on neuroimaging have not been well defined in prospective studies.

Clinically relevant intracranial abnormalities on neuroimaging occur in 11% of children with first, unprovoked seizures. Emergent/urgent abnormalities, however, occur in <1%, suggesting that most of these children do not require emergent neuroimaging. Specific clinical findings identify patients at higher risk. (Read the full article)




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Psychosocial Factors Associated With Adolescent Electronic Cigarette and Cigarette Use

Electronic cigarette (e-cigarette) use in adolescence is increasing. E-cigarette use has been associated with cigarette use, but there has been little study of other psychosocial risk factors for e-cigarette use and their relationship with cigarette use.

Approval and use of e-cigarettes and cigarettes among friends and family were strongly associated with cigarette and e-cigarette use in a cohort of adolescents in southern California. (Read the full article)




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Preterm Birth and Poor Fetal Growth as Risk Factors of Attention-Deficit/Hyperactivity Disorder

Infants born very prematurely or with a very low birth weight are known to have an increased risk of attention-deficit/hyperactivity disorder (ADHD). Results concerning late preterm children are controversial and studies examining fetal growth represented by weight for gestational age are scarce.

We demonstrate that each declining week of gestation increases the risk of ADHD. Also, late preterm infants have an increased risk. Furthermore, as weight for gestational age becomes smaller than 1 SD below the mean, the risk of ADHD increases. (Read the full article)




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Risk Factors for Central Nervous System Tuberculosis

Central nervous system (CNS) tuberculosis has high morbidity and mortality, and it frequently affects children aged <5 years.

In California, children who were US-born, Hispanic, and aged <5 years were at increased risk of CNS tuberculosis. Children with CNS tuberculosis were more likely to die. Specific populations of US-born infants might benefit from additional prevention measures. (Read the full article)




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Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy

John Penders
Aug 1, 2006; 118:511-521
ARTICLES




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The Relation of Overweight to Cardiovascular Risk Factors Among Children and Adolescents: The Bogalusa Heart Study

David S. Freedman
Jun 1, 1999; 103:1175-1182
ARTICLES




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Delaware moves to crack down on workplace fraud, improve oversight of contractors

WILMINGTON – Gov. John Carney signed a bill Tuesday that will clarify and enforce workplace fraud rules and create a new registry to oversee contractor activity in the First State. Senate Substitute 1 for Senate Bill 95 passed the Delaware General Assembly earlier this year with nearly unanimous support and incorporates recommendations from a 2018 […]



  • Department of Labor

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DOL Releases Guidance for Independent Contractors and Self-employed Seeking Unemployment Through the CARES Act

The Coronavirus Aid, Relief, and Economic Security (CARES) Act recently passed by the United States Congress and signed into law on March 27th provides unemployment assistance to independent contractors and those self-employed who have been affected by the Coronavirus.



  • Department of Labor
  • benefits
  • Coronavirus
  • Delaware Department of Labor
  • Division of Unemployment Insurance
  • unemployment insurance benefits



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NIST FIPS PUB 201-2: Personal Identity Verification of Federal Employees and Contractors DRAFT

Specifying architecture and technical requirements for a common identification standard for federal employees and contractors.




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Field Day: AI Startup Cultivates Robo Tractors for ‘Swarm Farming’ Disruption

Professional pyrotechnician Zack James is lighting his next fuse under the tractor market. The founder of Rabbit Tractors develops autonomous farm robots intended for multiple tasks and to be scaled up in number as needed, challenging traditional tractors. Based in northwest Indiana, Rabbit Tractors is a so-called swarm farming startup among a field of like-minded Read article >

The post Field Day: AI Startup Cultivates Robo Tractors for ‘Swarm Farming’ Disruption appeared first on The Official NVIDIA Blog.




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Introduction of disclosure obligations on the integration of ESG factors and risks

The European Commission published new Regulations on harmonised requirements in respect of sustainability-related disclosures and benchmarks contributing to sustainable finance (EU/2019/2089) (the “Disclosure Regulation”) in the Official...




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Legal Factors every non-profit must consider before expanding into new countries- The NGO Whisperer Magazine

...




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Quantum computer sets new record for finding prime number factors

A relatively small quantum computer has broken a number-factoring record, which may one day threaten data encryption methods that rely on factoring large numbers




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Health Tip: Risk Factors for Gestational Diabetes

Title: Health Tip: Risk Factors for Gestational Diabetes
Category: Health News
Created: 5/2/2008 2:00:00 AM
Last Editorial Review: 5/2/2008 12:00:00 AM




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Using Colonization Assays and Comparative Genomics To Discover Symbiosis Behaviors and Factors in Vibrio fischeri

ABSTRACT

The luminous marine Gram-negative bacterium Vibrio (Aliivibrio) fischeri is the natural light organ symbiont of several squid species, including the Hawaiian bobtail squid, Euprymna scolopes, and the Japanese bobtail squid, Euprymna morsei. Work with E. scolopes has shown how the bacteria establish their niche in the light organ of the newly hatched host. Two types of V. fischeri strains have been distinguished based upon their behavior in cocolonization competition assays in juvenile E. scolopes, i.e., (i) niche-sharing or (ii) niche-dominant behavior. This study aimed to determine whether these behaviors are observed with other V. fischeri strains or whether they are specific to those isolated from E. scolopes light organs. Cocolonization competition assays between V. fischeri strains isolated from the congeneric squid E. morsei or from other marine animals revealed the same sharing or dominant behaviors. In addition, whole-genome sequencing of these strains showed that the dominant behavior is polyphyletic and not associated with the presence or absence of a single gene or genes. Comparative genomics of 44 squid light organ isolates from around the globe led to the identification of symbiosis-specific candidates in the genomes of these strains. Colonization assays using genetic derivatives with deletions of these candidates established the importance of two such genes in colonization. This study has allowed us to expand the concept of distinct colonization behaviors to strains isolated from a number of squid and fish hosts.

IMPORTANCE There is an increasing recognition of the importance of strain differences in the ecology of a symbiotic bacterial species and, in particular, how these differences underlie crucial interactions with their host. Nevertheless, little is known about the genetic bases for these differences, how they manifest themselves in specific behaviors, and their distribution among symbionts of different host species. In this study, we sequenced the genomes of Vibrio fischeri isolated from the tissues of squids and fishes and applied comparative genomics approaches to look for patterns between symbiont lineages and host colonization behavior. In addition, we identified the only two genes that were exclusively present in all V. fischeri strains isolated from the light organs of sepiolid squid species. Mutational studies of these genes indicated that they both played a role in colonization of the squid light organ, emphasizing the value of applying a comparative genomics approach in the study of symbioses.




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APOBEC3C Tandem Domain Proteins Create Super Restriction Factors against HIV-1

ABSTRACT

Humans encode proteins, called restriction factors, that inhibit replication of viruses such as HIV-1. The members of one family of antiviral proteins, apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; shortened here to A3), act by deaminating cytidines to uridines during the reverse transcription reaction of HIV-1. The A3 locus encodes seven genes, named A3A to A3H. These genes have either one or two cytidine deaminase domains, and several of these A3s potently restrict HIV-1. A3C, which has only a single cytidine deaminase domain, however, inhibits HIV-1 only very weakly. We tested novel double domain protein combinations by genetically linking two A3C genes to make a synthetic tandem domain protein. This protein created a "super restriction factor" that had more potent antiviral activity than the native A3C protein, which correlated with increased packaging into virions. Furthermore, disabling one of the active sites of the synthetic tandem domain protein resulted in an even greater increase in the antiviral activity—recapitulating a similar evolution seen in A3F and A3G (double domain A3s that use only a single catalytically active deaminase domain). These A3C tandem domain proteins do not have an increase in mutational activity but instead inhibit formation of reverse transcription products, which correlates with their ability to form large higher-order complexes in cells. Finally, the A3C-A3C super restriction factor largely escaped antagonism by the HIV-1 viral protein Vif.

IMPORTANCE As a part of the innate immune system, humans encode proteins that inhibit viruses such as HIV-1. These broadly acting antiviral proteins do not protect humans from viral infections because viruses encode proteins that antagonize the host antiviral proteins to evade the innate immune system. One such example of a host antiviral protein is APOBEC3C (A3C), which weakly inhibits HIV-1. Here, we show that we can improve the antiviral activity of A3C by duplicating the DNA sequence to create a synthetic tandem domain and, furthermore, that the proteins thus generated are relatively resistant to the viral antagonist Vif. Together, these data give insights about how nature has evolved a defense against viral pathogens such as HIV.




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Historical Geography and Health Equity: An Exploratory View of North Carolina Slavery and Sociohealth Factors

Current health inequities are rooted in more than simple systems failures and inefficiencies. Historical legacy has corrupted health outcomes, and resolution requires both acknowledgment and intention.




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Transcription Factors BLH2 and BLH4 Regulate Demethylesterification of Homogalacturonan in Seed Mucilage

The polysaccharide pectin is a major component of the plant cell wall. The pectic glycan homogalacturonan (HG) is a proportionally small but important component of a specialized seed cell wall called mucilage. HG is synthesized in a highly methylesterified form, and, following secretion, is de-methylesterified by pectin methylesterases (PMEs). The degree of methylesterification of HG determines the structural and functional properties of pectin, but how methylesterification is regulated remains largely unknown. Here, we identified two BEL1-Like homeodomain (BLH) transcription factors, BLH2 and BLH4, as positive regulators of HG de-methylesterification in Arabidopsis (Arabidopsis thaliana) seed coat mucilage. BLH2 and BLH4 were significantly expressed in mucilage secretory cells during seed mucilage production. BLH2 and BLH4 single mutants exhibited no obvious mucilage phenotype, but the blh2 blh4 double mutant displayed significantly reduced mucilage adherence to the seed. Reduced mucilage adherence in blh2 blh4 was caused by decreased PME activity in the seed coat, which increased the degree of methylesterification of HG in mucilage. The expression of several PME metabolism-related genes, including PME58, PECTIN METHYLESTERASE INHIBITOR6, SEEDSTICK, and MYB52 was significantly altered in blh2 blh4 seeds. BLH2 and BLH4 directly activated PME58 expression by binding to its TGACAGGT cis-element. Moreover, pme58 mutants exhibited reduced mucilage adherence similar to that of blh2 blh4, and the blh2 blh4 pme58 triple mutant exhibited no additional mucilage adherence defects. Furthermore, overexpression of PME58 in blh2 blh4 rescued the mucilage adherence defect. Together, these results demonstrate that BLH2 and BLH4 redundantly regulate de-methylesterification of HG in seed mucilage by directly activating PME58.




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Factors associated with 30-day readmission for patients hospitalized for seizures

Background

We sought to determine the cumulative incidence of readmissions after a seizure-related hospitalization and identify risk factors and readmission diagnoses.

Methods

We performed a retrospective cohort study of adult patients hospitalized with a primary discharge diagnosis of seizure (International Classification of Diseases, Ninth Edition, Clinical Modification codes 345.xx and 780.3x) using the State Inpatient Databases across 11 states from 2009 to 2012. Hospital and community characteristics were obtained from the American Hospital Association and Robert Wood Johnson Foundation. We performed logistic regressions to explore effects of patient, hospital, and community factors on readmissions within 30 days of discharge.

Results

Of 98,712 patients, 13,929 (14%) were readmitted within 30 days. Reasons for readmission included epilepsy/convulsions (30% of readmitted patients), mood disorders (5%), schizophrenia (4%), and septicemia (4%). The strongest predictors of readmission were diagnoses of CNS tumor (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9–2.4) or psychosis (OR 1.8, 95% CI 1.7–1.8), urgent index admission (OR 2.0, 95% CI 1.8–2.2), transfer to nonacute facilities (OR 1.7, 95% CI 1.6–1.8), long length of stay (OR 1.7, 95% CI 1.6–1.8), and for-profit hospitals (OR 1.7, 95% CI 1.6–1.8). Our main model's c-statistic was 0.66. Predictors of readmission for status epilepticus included index admission for status epilepticus (OR 3.5, 95% CI 2.6–4.7), low hospital epilepsy volume (OR 0.4, 95% CI 0.3–0.7), and rural hospitals (OR 4.8, 95% CI 2.1–10.9).

Conclusion

Readmission is common after hospitalization for seizures. Prevention strategies should focus on recurrent seizures, the most common readmission diagnosis. Many factors were associated with readmission, although readmissions remain challenging to predict.




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Exploring Early Childhood Factors as an Avenue to Address Chronic Peer Victimization




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Early Childhood Factors Associated With Peer Victimization Trajectories From 6 to 17 Years of Age

OBJECTIVES:

To describe (1) the developmental trajectories of peer victimization from 6 to 17 years of age and (2) the early childhood behaviors and family characteristics associated with the trajectories.

METHODS:

We used data from 1760 children enrolled in the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Participants self-reported peer victimization at ages 6, 7, 8, 10, 12, 13, 15, and 17 years. Participants’ behavior and family characteristics were measured repeatedly between ages 5 months and 5 years.

RESULTS:

We identified 4 trajectories of peer victimization from 6 to 17 years of age: low (32.9%), moderate-emerging (29.8%), childhood-limited (26.2%), and high-chronic (11.1%). Compared with children in the low peer victimization trajectory, children in the other 3 trajectories were more likely to exhibit externalizing behaviors in early childhood, and those in the high-chronic and moderate-emerging trajectories were more likely to be male. Paternal history of antisocial behavior was associated with moderate-emerging (odds ratio [OR] = 1.54; 95% confidence interval [CI] = 1.09–2.19) and high-chronic (OR = 1.93; 95% CI = 1.25–2.99) relative to low peer victimization. Living in a nonintact family in early childhood was associated with childhood-limited (OR = 1.48; 95% CI = 1.11–1.97) and high-chronic (OR = 1.59; 95% CI = 1.09–2.31) relative to low peer victimization.

CONCLUSIONS:

Early childhood externalizing behaviors and family vulnerabilities were associated with the development of peer victimization. Some children entered the cascade of persistent peer victimization at the beginning of primary school. Support to these children and their families early in life should be an important component of peer victimization preventive interventions.




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The Paralogous Transcription Factors Stp1 and Stp2 of Candida albicans Have Distinct Functions in Nutrient Acquisition and Host Interaction [Molecular Pathogenesis]

Nutrient acquisition is a central challenge for all organisms. For the fungal pathogen Candida albicans, utilization of amino acids has been shown to be critical for survival, immune evasion, and escape, while the importance of catabolism of host-derived proteins and peptides in vivo is less well understood. Stp1 and Stp2 are paralogous transcription factors (TFs) regulated by the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing system and have been proposed to have distinct, if uncertain, roles in protein and amino acid utilization. We show here that Stp1 is required for proper utilization of peptides but has no effect on amino acid catabolism. In contrast, Stp2 is critical for utilization of both carbon sources. Commensurate with this observation, we found that Stp1 controls a very limited set of genes, while Stp2 has a much more extensive regulon that is partly dependent on the Ssy1 amino acid sensor (amino acid uptake and catabolism) and partly Ssy1 independent (genes associated with filamentous growth, including the regulators UME6 and SFL2). The ssy1/ and stp2/ mutants showed reduced fitness in a gastrointestinal (GI) colonization model, yet induced greater damage to epithelial cells and macrophages in a manner that was highly dependent on the growth status of the fungal cells. Surprisingly, the stp1/ mutant was better able to colonize the gut but the mutation had no effect on host cell damage. Thus, proper protein and amino acid utilization are both required for normal host interaction and are controlled by an interrelated network that includes Stp1 and Stp2.




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Factors Influencing Uptake of Changes to Clinical Preventive Guidelines

Background:

Despite widespread recognition that adherence to clinical preventive guidelines improves patient outcomes, clinicians struggle to implement guideline changes in a timely manner. Multiple factors influence guideline adoption and effective implementation. However, few studies evaluate their collective and inter-related effects. This qualitative study provides a comprehensive picture of the interplay between multiple factors on uptake of new or changed preventive guidelines.

Methods:

Semistructured interviews conducted in 2018 with a diverse sample of clinicians and practice leaders sought to understand patient, clinician, practice, health system, environment, and guideline factors of influence. An immersion-crystallization approach was used to identify emergent themes.

Results:

Interviewees expressed motivation to adhere to guidelines but also valued sharing decisions with patients. Personal biases and fears affected both clinician and patient guideline adoption. Practices facilitated implementation through workflow optimization and encouraging a culture of evidence-based practice while a key health system function was to maintain electronic health record alerts. More traditional environmental factors, such as insurance coverage or transportation, were less of a barrier to guideline adoption and implementation than the influence of media and specialists. Various specific guideline characteristics also affected ease of adoption and implementation. Different settings expressed greater health system, practice, or clinician-centric approaches to guideline implementation.

Conclusions:

Guideline uptake is influenced by a complex interplay of multiple levels of factors including the patient, clinician, practice, health system, environment, and guideline levels. Comprehensively understanding all levels of influence for each specific clinical setting may help to determine the optimal intervention(s) for improving uptake of evidence-based guidelines.




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The effect of ecological factors on eye morphology in the western rainbowfish, Melanotaenia australis [RESEARCH ARTICLE]

Thomas J. Lisney, Shaun P. Collin, and Jennifer L. Kelley

Ecological factors such as spatial habitat complexity and diet can explain variation in visual morphology, but few studies have sought to determine whether visual specialisation can occur among populations of the same species. We used a small Australian freshwater fish (the western rainbowfish, Melanotaenia australis) to determine whether populations showed variation in eye size and eye position, and whether this variation could be explained by environmental (light availability, turbidity) and ecological (predation risk, habitat complexity, invertebrate abundance) variables. We investigated three aspects of eye morphology, (1) eye size relative to body size, (2) pupil size relative to eye size, and (3) eye position in the head, for fish collected from 14 sites in a major river catchment in northwest Western Australia. We found significant variation among populations in all three measures of eye morphology, but no effect of sex on eye size or eye position. Variation in eye diameter and eye position was best explained by the level of habitat complexity. Specifically, fish occurring in habitats with low complexity (i.e. open water) tended to have smaller, more dorsally-located eyes, than those occurring in more complex habitats (i.e. vegetation present). The size of the pupil relative to the size of the eye was most influenced by the presence of surrounding rock formations; fish living in gorge habitats had significantly smaller pupils (relative to eye size) than those occupying semi-gorge sites or open habitats. Our findings reveal that different ecological and environmental factors contribute to habitat-specific visual specialisations within a species.




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Fixed Ratio Versus Lower Limit of Normal: Health Status and Risk Factors for COPD Overdiagnosis

BACKGROUND:The threshold of the lower limit of the normal range of lung function has been suggested to be more accurate than the 0.7 fixed ratio (FEV1/FVC < 0.7) for a diagnosis of COPD. We aimed to explore the health status and risk factors of patients overdiagnosed with COPD when using the lower limit of the normal range as a diagnostic reference.METHODS:Subjects with COPD diagnosed by a pulmonologist according to guidelines of the Global Initiative for Chronic Obstructive Lung Disease were recruited from October 2016 to April 2018. Overdiagnosed COPD was defined as FEV1/FVC that meets the criterion of the 0.7 fixed ratio but not the the lower limit of the normal range criterion. Spirometry and questionnaires were performed by eligible subjects.RESULTS:Of the 513 subjects included in the final analysis, 20 (3.9%) were overdiagnosed when using the lower limit of the normal range as the diagnostic reference. The subjects who were overdiagnosed were older, weighed more, had better lung function, lower modified Medical British Research Council scores, and higher St. George's Respiratory Questionnaire and 36-item Short Form Survey scores than the subjects who were correctly diagnosed. Older age, heavier weight, exposure to cooking oil fumes, or a new-built or newly renovated home were associated with an increased risk of overdiagnosis of COPD (age adjusted odds ratio (OR) 1.17, 95% CI 1.09–1.26; weight adjusted OR 1.08, 95% CI 1.03–1.13; exposure to cooking oil fumes adjusted OR 3.00, 95% CI, 1.04–8.68; exposure to new-built or newly renovated home adjusted OR 10.88, 95% CI 1.46–80.87.CONCLUSIONS:The subjects with overdiagnosed COPD had a better health status and lung function than the subjects who were correctly diagnosed. Older age, heavier weight, and exposure to cooking oil fumes or a new-built or newly renovated home were factors associated with the overdiagnosis of COPD. These findings may help reduce overdiagnosis of COPD.




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The ubiquitin hydrolase Doa4 directly binds Snf7 to inhibit recruitment of ESCRT-III remodeling factors in S. cerevisiae [RESEARCH ARTICLE]

Dalton Buysse, Anna-Katharina Pfitzner, Matt West, Aurelien Roux, and Greg Odorizzi

The ESCRT-III protein complex executes reverse-topology membrane scission. The scission mechanism is unclear but is linked to remodeling of ESCRT-III complexes at the membrane surface. At endosomes, ESCRT-III mediates the budding of intralumenal vesicles (ILVs). In Saccharomyces cerevisiae, ESCRT-III activity at endosomes is regulated through an unknown mechanism by Doa4, an ubiquitin hydrolase that deubiquitylates transmembrane proteins sorted into ILVs. We report that the non-catalytic N-terminus of Doa4 binds Snf7, the predominant ESCRT-III subunit. Through this interaction, Doa4 overexpression alters Snf7 assembly status and inhibits ILV membrane scission. In vitro, the Doa4 N-terminus inhibits association of Snf7 with Vps2, which functions with Vps24 to arrest Snf7 polymerization and remodel Snf7 polymer structure. In vivo, Doa4 overexpression inhibits Snf7 interaction with Vps2 and also with the ATPase Vps4, which is recruited by Vps2 and Vps24 to remodel ESCRT-III complexes by catalyzing subunit turnover. Our data suggest a mechanism by which the deubiquitylation machinery regulates ILV biogenesis by interfering with ESCRT-III remodeling.




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Prevalence and incidence of, and risk factors for chronic cough in the adult population: the Rotterdam Study

Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects.

In a prospective population-based cohort study among subjects aged ≥45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations.

Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6–12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough.

Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease.




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Evaluation of Factors Related to Glycemic Management in Professional Cyclists With Type 1 Diabetes Over a 7-Day Stage Race

OBJECTIVE

To investigate factors related to glycemic management among members of a professional cycling team with type 1 diabetes over a 7-day Union Cycliste Internationale World Tour stage race.

RESEARCH DESIGN AND METHODS

An observational evaluation of possible factors related to glycemic management and performance in six male professional cyclists with type 1 diabetes (HbA1c 6.4 ± 0.6%) during the 2019 Tour of California.

RESULTS

In-ride time spent in euglycemia (3.9–10.0 mmol/L glucose) was 63 ± 11%, with a low percentage of time spent in level 1 (3.0–3.9 mmol/L; 0 ± 1% of time) and level 2 (<3.0 mmol/L; 0 ± 0% of time) hypoglycemia over the 7-day race. Riders spent 25 ± 9% of time in level 1 (10.1–13.9 mmol/L) and 11 ± 9% in level 2 (>13.9 mmol/L) hyperglycemia during races. Bolus insulin use was uncommon during races, despite high carbohydrate intake (76 ± 23 g ⋅ h–1). Overnight, the riders spent progressively more time in hypoglycemia from day 1 (6 ± 12% in level 1 and 0 ± 0% in level 2) to day 7 (12 ± 12% in level 1 and 2 ± 4% in level 2) (2[1] > 4.78, P < 0.05).

CONCLUSIONS

Professional cyclists with type 1 diabetes have excellent in-race glycemia, but significant hypoglycemia during recovery overnight, throughout a 7-day stage race.




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Immunosuppression and growth factors for severe aplastic anemia: new data for old questions




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Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA1c was the most significant risk factor for DPN, followed by older age, longer duration, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by higher mean HbA1c, sustained albuminuria, longer duration of type 1 diabetes, higher mean pulse rate, higher mean systolic blood pressure, β-blocker use, estimated glomerular filtration rate <60 mL/min/1.73 m2, higher most recent pulse rate, and cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.




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Association between media attention and presentation of vaccination information on Canadian chiropractors websites: a prospective mixed-methods cohort study

Background:

Historically, some chiropractors have been critical of vaccination, and this has been the subject of recent media attention in Canada. We explored the association between media attention and public dissemination of vaccination information on Canadian chiropractors’ websites.

Methods:

In 2016, we identified all Canadian chiropractors’ websites that provided information on vaccination by extracting details from the regulatory college website for each province using the search engine on their "find a chiropractor" page. We assessed the quality of information using the Web Resource Rating Tool (scores range from 0% [worst] to 100% [best]), determined whether vaccination was portrayed in a positive, neutral or negative manner, and conducted thematic analysis of vaccination content. We revisited all identified websites in 2019 to explore for changes to posted vaccination material.

Results:

In July 2016, of 3733 chiropractic websites identified, 94 unique websites provided information on vaccination: 59 (63%) gave negative messaging, 19 (20%) were neutral and 16 (17%) were positive. The quality of vaccination content on the websites was generally poor, with a median Web Resource Rating Tool score of 19%. We identified 4 main themes: there are alternatives to vaccination, vaccines are harmful, evidence regarding vaccination and health policy regarding vaccination. From 2012 to 2016, there was 1 Canadian newspaper story concerning antivaccination statements by chiropractors, whereas 51 news articles were published on this topic between 2017 and 2019. In April 2019, 45 (48%) of the 94 websites we had identified in 2016 had removed all vaccination content or had been discontinued.

Interpretation:

In 2016, a minority of Canadian chiropractors provided vaccination information on their websites, the majority of which portrayed vaccination negatively. After substantial national media attention, about half of all vaccination material on chiropractors’ websites was removed within several years.




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CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

MATERIALS AND METHODS:

Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation.

RESULTS:

The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions.

CONCLUSIONS:

Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome.




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