Interpersonal touch is emerging as an important topic in the study of adult relationships, with recent research showing that such behaviors can promote better relationship functioning and individual ...well-being. This investigation considers whether being hugged is associated with reduced conflict-related decreases in positive affect and increases in negative affect as well as whether these associations differ between women and men. A sample of 404 adults were interviewed every night for 14 consecutive days about their conflicts, hug receipt, and positive and negative affect. Results indicated that there was an interaction between hug receipt and conflict exposure such that receiving a hug was associated with a smaller conflict-related decrease in positive affect and a smaller conflict-related increase in negative affect when assessed concurrently. Hug receipt was also prospectively associated with a smaller conflict-related increase in next day negative affect but was not associated with next day positive affect. Associations between hug receipt and conflict-related changes in affect did not differ between women and men, between individuals who were married or in a marital-like relationship and those who were not, or as a function of individual differences in baseline perceived social support. While correlational, these results are consistent with the hypothesis that hugs buffer against deleterious changes in affect associated with experiencing interpersonal conflict. Possible mechanisms through which hugs facilitate positive adaptation to conflict are discussed.
Iron copper zeolite (Fe‐Cu‐ZSM‐5) with aqueous hydrogen peroxide is active for the selective oxidation of methane to methanol. Iron is involved in the activation of the carbon–hydrogen bond, while ...copper allows methanol to form as the major product. The catalyst is stable, re‐usable and activates methane giving >90 % methanol selectivity and 10 % conversion in a closed catalytic cycle (see scheme).
Summary Background Indices of cortisol activity, including the cortisol awakening response (CAR), diurnal slope, and cortisol output across the day (total daily output), are often studied as ...mechanistic indicators that could link stress with health. Yet there is a paucity of data speaking to their temporal features, particularly whether they behave in a more state- or trait-like manner across time. Methods To address this issue, data from 3 studies were used to assess CAR, diurnal slope and total daily output stability over different age groups and time spans: 130 healthy children and adolescents collected salivary cortisol samples 5 times/day (1, 4, 9 and 11 h after wake) over 2 days at 5 visits spaced 6 months apart (Study 1); 147 adolescent girls collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 2 days at 3 visits, each a year apart (Study 2); and 47 healthy, primarily middle age adults collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 3 days at 4 visits spaced 2–3 months apart (Study 3). Stability was estimated by multilevel model-derived intraclass correlation coefficients ( ICC s). Results Across studies, approximately 50% of the variance in cortisol indices was attributable to day-to-day fluctuations, suggesting state-like properties. Of the indices, total daily output emerged as the most stable over time, followed by diurnal slope and CAR, but stability estimates were generally quite modest regardless of index and sample. Over time spans of >1 year, ICC s were ≤ .13. Conclusions Most of the variance in CAR, diurnal slope and total daily output reflects day-to-day fluctuation; there was little evidence for more stable trait-like influences. These findings suggest that future research should focus on short-term fluctuations in stress, cortisol and health, as opposed to lengthy disease processes.
Abstract Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress ...influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol’s anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16− cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers’ decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups’ monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects’ monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases.
Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact ...of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment.
Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed.
Significant improvements in FEV
, BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03).
Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.
Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these ...patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown.
DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m
, and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP.
Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036-1238) vs 1191 pg/dL (95% CI 1089-1304),
=0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal
=0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98-3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1-3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all
values for interaction=NS).
In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02653482.
Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be ...involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed. This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease—most notably in the field of immunotherapies—the options for nail psoriasis are far more limited. While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen. Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease.
The use of liquid biopsies for cancer detection and management is rapidly gaining prominence
. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using ...cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations
. By contrast, large-scale epigenetic alterations-which are tissue- and cancer-type specific-are not similarly constrained
and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns.
Although responses to different stressors are sometimes assumed to be similar, recent research has demonstrated that certain types of stress, such as targeted rejection, are particularly potent. To ...test such associations in a chronic-disease model, we examined how noninterpersonal, interpersonal, and targeted-rejection major life events predicted changes in gene expression and symptom severity in 121 youths with asthma who were assessed every 6 months for 2 years. Youths who had recently experienced targeted rejection had lower messenger RNA expression for signaling molecules that control airway inflammation and obstruction (specifically, the glucocorticoid receptor and β2-adrenergic receptor) than youths who had not experienced targeted rejection. These associations were specific to targeted rejection and stronger for youths higher in subjective social status. Higher-status youths exposed to targeted rejection (but not other types of stress) also reported more asthma symptoms. These data demonstrate stressor-specific associations with molecular-signaling pathways and the severity of asthma, and they suggest that threats to the social self may be particularly deleterious.
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