Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study.

BACKGROUND: The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown. METHODS: Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study. CONCLUSION: The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276441.

The impact of short-term predominate breastfeeding on cognitive outcome at 5 years.

AIM: Breastfeeding is associated with IQ, school attendance and income. Despite the known benefits of breastfeeding, the rate of exclusive breastfeeding up to 6 months is low globally. We examined the effect of short-term breastfeeding on long-term IQ. METHODS: In this secondary analysis of the prospective Cork BASELINE Birth Cohort Study, children were categorised as predominantly breastfed (n = 288) versus exclusively formula-fed (n = 254) at 2-months of age. Infants (n = 404) receiving mixed feeding were excluded. Outcome was assessed using the KBIT-II at 5 years. Multivariable linear regression was used to adjust for confounding variables. RESULTS: Following adjustment for confounding variables, children, predominately breastfed at 2 months of age, demonstrated increased overall IQ (2.00 points (95% CI: 0.35 to 3.65); P = .018) and non-verbal IQ at 5 years of age (1.88 points (95% CI: 0.22 to 3.54); P = .027) compared with those never breastfed. No significant relationship was found with verbal IQ (P = .154). CONCLUSION: A significant increase in composite and non-verbal IQ at 5 years of age was associated with short-term breastfeeding. This study adds to a growing body of evidence that short-term breastfeeding promotes healthy cognitive development.

Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. adults.

BACKGROUND: The success of vaccination efforts to curb the COVID-19 pandemic will require broad public uptake of immunization and highlights the importance of understanding factors associated with willingness to receive a vaccine. METHODS: U.S. adults aged 65 and older enrolled in the HeartlineTM clinical study were invited to complete a COVID-19 vaccine assessment through the HeartlineTM mobile application between November 6-20, 2020. Factors associated with willingness to receive a COVID-19 vaccine were evaluated using an ordered logistic regression as well as a Random Forest classification algorithm. RESULTS: Among 9,106 study participants, 81.3% (n = 7402) responded and had available demographic data. The majority (91.3%) reported a willingness to be vaccinated. Factors most strongly associated with vaccine willingness were beliefs about the safety and efficacy of COVID-19 vaccines and vaccines in general. Women and Black or African American respondents reported lower willingness to vaccinate. Among those less willing to get vaccinated, 66.2% said that they would talk with their health provider before making a decision. During the study, positive results from the first COVID-19 vaccine outcome study were released; vaccine willingness increased after this report. CONCLUSIONS: Even among older adults at high-risk for COVID-19 complications who are participating in a longitudinal clinical study, 1 in 11 reported lack of willingness to receive COVID-19 vaccine in November 2020. Variability in vaccine willingness by gender, race, education, and income suggests the potential for uneven vaccine uptake. Education by health providers directed toward assuaging concerns about vaccine safety and efficacy can help improve vaccine acceptance among those less willing. TRIAL REGISTRATION: Clinicaltrials.gov NCT04276441.

Infant skin microstructure assessed in vivo differs from adult skin in organization and at the cellular level.

Functional differences between infant and adult skin may be attributed to putative differences in skin microstructure. The purpose of this study was to examine infant skin microstructure in vivo and to compare it with that of adult skin. The lower thigh area of 20 healthy mothers (ages 25-43) and their biological children (ages 3-24 months) was examined using in vivo noninvasive methods including fluorescence spectroscopy, video microscopy, and confocal laser scanning microscopy. Stratum corneum and supra-papillary epidermal thickness as well as cell size in the granular layer were assessed from the confocal images. Adhesive tapes were used to remove corneocytes from the outer-most layer of stratum corneum and their size was computed using image analysis. Surface features showed differences in glyph density and surface area. Infant stratum corneum was found to be 30% and infant epidermis 20% thinner than in adults. Infant corneocytes were found to be 20% and granular cells 10% smaller than adult corneocytes indicating a more rapid cell turnover in infants. This observation was confirmed by fluorescence spectroscopy. Dermal papillae density and size distribution also differed. Surprisingly, a distinct direct structural relationship between the stratum corneum morphology and the dermal papillae was observed exclusively in infant skin. A change in reflected signal intensity at approximately 100 mum indicating the transition between papillary and reticular dermis was evident only in adult skin. We demonstrate in vivo qualitative and quantitative differences in morphology between infant and adult skin. These differences in skin microstructure may help explain some of the reported functional differences.

Implicit Maternal Intuition Confidence Is Associated With Maternal Well-Being Across Cultures.

The transition to motherhood involves the experience of each individual mother and child, as well as the burden of cultural expectations. Social desirability demands may impede self reports of difficulties during the transition to motherhood when using traditional explicit measures. One core component of maternal role attainment is a mother's confidence in her own intuitive knowledge of her child. This brief report presents two studies that examine a "low technology" implicit measure of maternal intuition confidence that is based within a more general decision confidence paradigm. Study 1 examined the association of both implicit and explicit maternal intuition confidence with depressive symptoms, life satisfaction, and maternal identity satisfaction in a United States sample of mothers. The implicit measure contributed to variance in each of the outcome measures, above and beyond an explicit measure. Study 2 explored the association of implicit maternal intuition confidence with life satisfaction and maternal identity satisfaction in Brazil, China, India, the United States and the United Kingdom. Across all samples, implicit maternal intuition confidence was significantly associated with satisfaction with life. However, it was significantly associated with maternal identity satisfaction only in the two individualistic countries (the United States and the United Kingdom), but not in the three collectivist countries.

Cyclic strain inhibits switching of smooth muscle cells to an osteoblast-like phenotype.

Ectopic calcification is commonly associated with cardiovascular disease, injury, aging, and biomaterial implantation. We hypothesized that the normal mechanical environment of smooth muscle cells (SMCs) inhibits a phenotypic switch to a pattern of gene expression more typical for bone and inducive for calcification. This hypothesis was tested using a 3-D engineered smooth muscle tissue model subjected to cyclic mechanical strain. This simplified model maintained a 3-D tissue architecture while eliminating systemic effects as can be seen with in vivo models. All engineered tissues were found to express bone-associated genes (osteopontin, matrix gla protein, alkaline phosphatase, and the transcription factor CBFA-1). Strikingly, however, expression of these genes was down-regulated in tissues exposed to cyclic strain at all time points ranging from 5 to 150 days. Furthermore, long-term strain played a protective role in regard to calcification, as unstrained tissues exhibited increased calcium deposition with respect to strained tissues. The results of this study suggest that without an appropriate mechanical environment, SMCs in 3-D culture undergo a phenotypic conversion to an osteoblast-like pattern of gene expression. This finding has significant implications for the mechanisms underlying a variety of cardiovascular diseases and indicates the broad utility of engineered tissue models in basic biology studies.

Sleep patterns and sleep disturbances across pregnancy.

OBJECTIVE: This study sought to characterize sleep patterns and sleep problems in a large sample of women across all months of pregnancy. METHODS: A total of 2427 women completed an Internet-based survey that included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, vitality scale of the Short Form 36 Health Survey (SF-36), Insomnia Severity Index (ISI), Berlin questionnaire, International Restless Legs Syndrome (IRLS) question set, and a short version of the Pregnancy Symptoms Inventory (PSI). RESULTS: Across all months of pregnancy, women experienced poor sleep quality (76%), insufficient nighttime sleep (38%), and significant daytime sleepiness (49%). All women reported frequent nighttime awakenings (100%), and most women took daytime naps (78%). Symptoms of insomnia (57%), sleep-disordered breathing (19%), and restless legs syndrome (24%) were commonly endorsed, with no difference across the month of pregnancy for insomnia, sleep-disorder breathing, daytime sleepiness, or fatigue. In addition, high rates of pregnancy-related symptoms were found to disturb sleep, especially frequent urination (83%) and difficulty finding a comfortable sleep position (79%). CONCLUSIONS: Women experience significant sleep disruption, inadequate sleep, and high rates of symptoms of sleep disorder throughout pregnancy. These results suggest that all women should be screened and treated for sleep disturbances throughout pregnancy, especially given the impact of inadequate sleep and sleep disorders on fetal, pregnancy, and postpartum outcomes.

Quantification of fibronectin adsorption to silicone-rubber cell culture substrates.

As the role of mechanical force in cellular signaling gained recognition, investigators designed a number of devices to deliver controlled regimens of mechanical force to cultured cells. One type of device uses thin silicone-rubber membranes to support monolayer cell adhesion and to transmit mechanical force in the form of biaxial strain. We have observed that cell attachment and spreading are impaired on these membranes compared to polystyrene, even when both are passively coated with identical amounts of extracellular matrix. The purpose of these studies was to quantify the efficiency and stability of passive matrix adsorption onto commercially available elastic culture substrates. A theoretically saturating density (1 microg/cm2) of fibronectin was added to each well, and the initial efficiency of adsorption to the walls and elastic membranes was found to be 31 +/- 2% of the protein added. Strikingly, when the protein adsorbed specifically to the membranes was quantified after seven days, only 10-26 ng/cm2 fibronectin were present, revealing that most of the adsorption is to the sides of the wells. These results indicate that the adsorption of matrix proteins to silicone-rubber substrates is relatively inefficient and that investigators who use these systems must be aware of this fact and design their experiments accordingly.

Elastic biodegradable poly(glycolide-co-caprolactone) scaffold for tissue engineering.

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, and it would be necessary for the development of the elastic scaffolds if one wishes to engineer SM tissues under cyclic mechanical loading. This study reports on the development of an elastic scaffold fabricated from a biodegradable polymer. Biodegradable poly(glycolide-co-caprolactone) (PGCL) copolymer was synthesized from glycolide and epsilon-caprolactone in the presence of stannous octoate as catalyst. The copolymer was characterized by (1)H-NMR, gel permeation chromatography and differential scanning calorimetry. Scaffolds for tissue engineering applications were fabricated from PGCL copolymer using the solvent-casting and particle-leaching technique. The PGCL scaffolds produced in this fashion had open pore structures (average pore size = 250 microm) without the usual nonporous skin layer on external surfaces. Mechanical testing revealed that PGCL scaffolds were far more elastic than poly(lactic-co-glycolic acid) (PLGA) scaffolds fabricated using the same method. Tensile mechanical tests indicated that PGCL scaffolds could withstand an extension of 250% without cracking, which was much higher than withstood by PLGA scaffolds (10-15%). In addition, PGCL scaffolds achieved recoveries exceeding 96% at applied extensions of up to 230%, whereas PLGA scaffolds failed (cracked) at an applied strain of 20%. Dynamic mechanical tests showed that the permanent deformation of the PGCL scaffolds in a dry condition produced was less than 4% of the applied strain, when an elongation of 20% at a frequency of 1 Hz (1 cycle per second) was applied for 6 days. Moreover, PGCL scaffolds in a buffer solution also had permanent deformations less than 5% of the applied strain when an elongation of 10% at a frequency of 1 Hz was applied for 2 days. The usefulness of the PGCL scaffolds was demonstrated by engineering SM tissues in vivo. This study shows that the elastic PGCL scaffolds produced in this study could be used to engineer SM-containing tissues (e.g. blood vessels and bladders) in mechanically dynamic environments.

Mechanical stimulation and mitogen-activated protein kinase signaling independently regulate osteogenic differentiation and mineralization by calcifying vascular cells.

Ectopic calcification of vascular tissue is associated with several cardiovascular pathologies and likely involves active regulation by vascular smooth muscle cells and osteoblast-like vascular cells. This process often occurs in sites with altered mechanical environments, suggesting a role for mechanical stimuli in calcification. In this study, we investigated the effect of mechanical stimulation on the proliferation, osteogenic differentiation, calcification, and mitogen-activated protein kinase (MAPK) signaling in calcifying vascular cells (CVCs), a subpopulation of aortic smooth muscle cells putatively involved in vascular calcification. Application of equibiaxial cyclic strain (7%, 0.25 Hz) to CVCs had no effect on cell proliferation, but accelerated alkaline phosphatase expression and significantly increased mineralization by 3.1-fold over unstrained cells. Fluid motion in the absence of strain also enhanced mineralization, but to a lesser degree. Because MAPK pathways mediate mechanically regulated osteoblast differentiation, we tested whether similar signaling was involved in mineralization by CVCs. In static cultures, pharmacological inhibition of the extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase pathways significantly attenuated mineral production by as much as -94%, compared with uninhibited CVCs. Strikingly, although mechanical stimulation activated each of the MAPK pathways, inhibition of these pathways had no effect on the mechanically induced enhancement of alkaline phosphatase activity or mineralization. These novel data indicate that mechanical signals regulate calcification by CVCs, and although MAPK signaling is critical to CVC osteogenic differentiation and mineralization, it is not involved directly in transduction of mechanical signals to regulate these processes under the conditions utilized in this study.

Diversity of the human skin microbiome early in life.

Within days after birth, rapid surface colonization of infant skin coincides with significant functional changes. Gradual maturation of skin function, structure, and composition continues throughout the first years of life. Recent reports have revealed topographical and temporal variations in the adult skin microbiome. Here we address the question of how the human skin microbiome develops early in life. We show that the composition of cutaneous microbial communities evolves over the first year of life, showing increasing diversity with age. Although early colonization is dominated by Staphylococci, their significant decline contributes to increased population evenness by the end of the first year. Similar to what has been shown in adults, the composition of infant skin microflora appears to be site specific. In contrast to adults, we find that Firmicutes predominate on infant skin. Timely and proper establishment of healthy skin microbiome during this early period might have a pivotal role in denying access to potentially infectious microbes and could affect microbiome composition and stability extending into adulthood. Bacterial communities contribute to the establishment of cutaneous homeostasis and modulate inflammatory responses. Early microbial colonization is therefore expected to critically affect the development of the skin immune function.

Impact of a group mind/body intervention on pregnancy rates in IVF patients.

OBJECTIVE: To determine if women who were randomized to a mind/body program before starting their first IVF cycle would have higher pregnancy rates than control subjects. DESIGN: Randomized, controlled, prospective study. SETTING: Private academically affiliated infertility center. PATIENT(S): A total of 143 women aged≤40 years who were about to begin their first IVF cycle. INTERVENTION(S): Subjects were randomized to a ten-session mind/body program (MB) or a control group and followed for two IVF cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Only 9% of the MB participants had attended at least one-half of their sessions at cycle 1 start. Pregnancy rates for cycle 1 were 43% for all subjects; 76% of the MB subjects had attended at least one-half of their sessions at cycle 2 start. Pregnancy rates for cycle 2 were 52% for MB and 20% for control. CONCLUSION(S): MB participation was associated with increased pregnancy rates for cycle 2, prior to which most subjects had attended at least half of their sessions.

Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life.

Skin water barrier development begins in utero and is believed to be complete by week 34 of gestational age. The goal of this investigation was to assess the dynamic transport and distribution of water of the stratum corneum of infants and compare it to those of adults. The interaction of water with the stratum corneum was assessed by measuring capacitance, transepidermal water loss (TEWL), rates of absorption-desorption as well as Raman spectra as a function of depth (a total of 124 infants (3-12 months) and 104 adults (14-73 years)). The results show that capacitance, TEWL, and absorption-desorption rates had larger values consistently for infant stratum corneum throughout the first year of life and showed greater variation than those of adults. The Raman spectra analyzed for water and for the components of natural moisturizing factor (NMF) showed the distribution of water to be higher and have a steeper gradient in infants than in adults; the concentration of NMF was significantly lower in infants. The results suggest that although the stratum corneum of infants may appear intact shortly after birth (<1 month), the way it stores and transports water becomes adult-like only after the first year of life.