Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A(4)/1A(5)haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted

Design as a provocation to support discussion about euthanasia: The Plug

Design as a provocation to support discussion about euthanasia: The Plu

Evaluation of 15 Functional Candidate Genes for Association with Chronic Otitis Media with Effusion and/or Recurrent Otitis Media (COME/ROM)

DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology

Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: a-10 year prospective population-based study

Background:&nbsp;Age-related losses in bone mineral density (BMD), muscle strength, balance, and gait have been linked to&nbsp;an increased risk of falls, fractures and disability, but few prospective studies have compared the timing, rate and pattern&nbsp;of changes in each of these measures in middle-aged and older men and women. This is important so that targeted&nbsp;strategies can be developed to optimise specific musculoskeletal and functional performance measures in older adults.&nbsp;Thus, the aim of this 10-year prospective study was to: 1) characterize and compare age- and gender-specific changes in&nbsp;BMD, grip strength, balance and gait in adults aged 50 years and over, and 2) compare the relative rates of changes&nbsp;between each of these musculoskeletal and functional parameters with ageing.Methods: Men (n = 152) and women (n = 206) aged 50, 60, 70 and 80 years recruited for a population-based study had&nbsp;forearm BMD, grip strength, balance and gait velocity re-assessed after 10-years.Results: The annual loss in BMD was 0.5-0.7% greater in women compared to men aged 60 years and older&nbsp;(p &lt; 0.05- &lt; 0.001), but there were no gender differences in the rate of loss in grip strength, balance or gait. From the age&nbsp;of 50 years there was a consistent pattern of loss in grip strength, while the greatest deterioration in balance and gait&nbsp;occurred from 60 and 70 years onwards, respectively. Comparison of the changes between the different measures&nbsp;revealed that the annual loss in grip strength in men and women aged &lt;70 years was 1-3% greater than the decline in&nbsp;BMD, balance and gait velocity.Conclusion: There were no gender differences in the timing (age) and rate (magnitude) of decline in grip strength,&nbsp;balance or gait in Swedish adults aged 50 years and older, but forearm BMD decreased at a greater rate in women than&nbsp;in men. Furthermore, there was heterogeneity in the rate of loss between the different musculoskeletal and function&nbsp;parameters, especially prior to the age of 70 years, with grip strength deteriorating at a greater rate than BMD,&nbsp;balance and gait.</div

Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography

A continuous infusion of a single high dose of dobutamine has been, recently, suggested as a simple and effective protocol of stress echocardiography. The present study assesses the feasibility, safety, and tolerability of an accelerated dobutamine stress protocol performed in patients with suspected or known coronary artery disease. Two hundred sixty five consecutive patients underwent accelerated dobutamine stress echocardiography: the dobutamine was administered at a constant dose of 50 μg/kg/min for up to 10 minutes. The mean weight-adjusted cumulative dose of dobutamine used was 330 ± 105.24 μg/kg. Total duration of dobutamine infusion was 6.6 ± 2.1 min. Heart rate rose from 69.9 ± 12.1 to 123.1 ± 22.1 beats/min at peak with a concomitant change in systolic blood pressure (127.6 ± 18.1 vs. 167.6 ± 45.0 mmHg). Dobutamine administration produced a rapid increase in heart rate (9.4 ± 5.9 beats/min2). The side effects were similar to those described with the standard protocol; the most common were frequent premature ventricular complexes (21.5%), frequent premature atrial complexes (1.5%) and non sustained ventricular tachycardia (1.5%); among non cardiac symptoms the most frequent were nausea (3.4%), headache (1.1%) and symptomatic hypotension (1.1%). No major side effects were observed during the test. Our data demonstrate that a continous infusion of a single high dose of dobutamine is a safe and well tolerated method of performing stress echocardiography in patients with suspected or known coronary artery disease. This new protocol requires the administration of lower cumulative dobutamine dose than standard protocol and results in a significant reduction in test time

Linking evapotranspiration seasonal cycles to the water balance of headwater catchments with contrasting land uses

Land use affects evapotranspiration rates and is a primary driver of the catchment water balance. The water balance of two catchments in southeastern Australia dominated by either grazed pasture or blue gum (Eucalyptus globulus) plantation was studied, focusing on the patterns of evapotranspiration (ET) throughout the year. Rainfall, streamflow, and groundwater levels measured between 2015 and 2019 were combined to estimate annual ET using a water balance equation. In the pasture, eddy covariance was used to measure ET from the catchment. Sap flow measurements were used to estimate tree transpiration in May 2017–May 2018 and Feb 2019–Feb 2021 in two different plots within the plantation. The tree transpiration rates were added to interception, estimated as a percentage of annual rainfall, to calculate ET from the plantation catchment. ET in the pasture showed strong seasonal cycles with very low ET rates in summer and ET rates in spring that were larger than the transpiration rates in the plantation, where trees transpired consistently throughout the year. The estimated annual ET from the water balance equation was comparable to ET estimated from other measurements. In the pasture, ET on average accounted for 88% of annual rainfall, while ET in the plantation was on average 93% of rainfall, exceeding it in the years with annual rainfall lower than about 500 mm. The difference between the ET rates in the plantation and the pasture was approximately 30–50 mm y−1. The larger ET rates in the plantation were reflected in a gradual decrease in the groundwater storage. The larger ET rates were enough to cause a decrease in groundwater storage in the plantation but not in the pasture, where groundwater levels remained stable

A qualitative study of carers' experiences of dementia cafes : a place to feel supported and be yourself

Abstract Background Unpaid, informal carers or caregivers play an important role in supporting people living with dementia but the role can be challenging and carers themselves may benefit from support. Alzheimer’s, dementia or memory cafés are one such form of support . These cafés are usually provided in the voluntary sector and are a place where people with dementia and those supporting them, usually family carers, can meet with others in similar situations. Methods Using semi-structured interviews, this qualitative study explored the experiences of 11 carers from five dementia cafés in and around London, England. Results Thematic analysis resulted in the identification of four key themes. Cafés provide a relaxed, welcoming atmosphere where carers can go where they feel supported and accepted. Café attendance often brought a sense of normality to these carers’ lives. Carers and those they care for look forward to going and often enjoy both the activities provided and socialising with others. Other highlighted benefits included peer support from other carers, information provision and support from the volunteer café coordinators. Despite diversity in how the cafés were run and in the activities offered, there were many reported similarities amongst carers in the value ascribed to attending the cafés. Conclusions Dementia cafés appear to be a valuable, perhaps unique form of support for carers giving them brief respite from their caring role. Future research incorporating mixed methods is needed to understand the perspectives of those living with dementia

Barriers to implementation of a computerized decision support system for depression: an observational report on lessons learned in "real world" clinical settings

<p>Abstract</p> <p>Background</p> <p>Despite wide promotion, clinical practice guidelines have had limited effect in changing physician behavior. Effective implementation strategies to date have included: multifaceted interventions involving audit and feedback, local consensus processes, marketing; reminder systems, either manual or computerized; and interactive educational meetings. In addition, there is now growing evidence that contextual factors affecting implementation must be addressed such as organizational support (leadership procedures and resources) for the change and strategies to implement and maintain new systems.</p> <p>Methods</p> <p>To examine the feasibility and effectiveness of implementation of a computerized decision support system for depression (CDSS-D) in routine public mental health care in Texas, fifteen study clinicians (thirteen physicians and two advanced nurse practitioners) participated across five sites, accruing over 300 outpatient visits on 168 patients.</p> <p>Results</p> <p>Issues regarding computer literacy and hardware/software requirements were identified as initial barriers. Clinicians also reported concerns about negative impact on workflow and the potential need for duplication during the transition from paper to electronic systems of medical record keeping.</p> <p>Conclusion</p> <p>The following narrative report based on observations obtained during the initial testing and use of a CDSS-D in clinical settings further emphasizes the importance of taking into account organizational factors when planning implementation of evidence-based guidelines or decision support within a system.</p

Non-Raft AC2 Defines a cAMP Signaling Compartment That Selectively Regulates IL-6 Expression in Airway Smooth Muscle Cells

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was induced by Fsk and select G protein-coupled receptor (GPCR) agonists, though IL-6 levels did not directly correlate with global cAMP levels. Treatment with PKA selective 6-Bnz-cAMP or Epac selective 8-CPT-2Me-cAMP cAMP analogs revealed a predominant role for PKA in cAMP-mediated induction of IL-6. IL-6 promoter mutations demonstrated that AP-1 and CRE transcription sites were required for Fsk to stimulate IL-6 expression. Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in BSMC via Epac and PKA and demonstrates that other AC isoforms are excluded from this pool