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Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. However, underlying molecular mechanisms are insufficiently understood. Previous studies suggested that microRNA (miRNA) dependent gene regulation plays an important role in the initiation and maintenance of AF. The 2‐pore‐domain potassium channel TASK‐1 (tandem of P domains in a weak inward rectifying K+ channel–related acid sensitive K+ channel 1) is an atrial‐specific ion channel that is upregulated in AF. Inhibition of TASK‐1 current prolongs the atrial action potential duration to similar levels as in patients with sinus rhythm. Here, we hypothesize that miRNAs might be responsible for the regulation of KCNK3 that encodes for TASK‐1. Methods and Results We selected miRNAs potentially regulating KCNK3 and studied their expression in atrial tissue samples obtained from patients with sinus rhythm, paroxysmal AF, or permanent/chronic AF. MiRNAs differentially expressed in AF were further investigated for their ability to regulate KCNK3 mRNA and TASK‐1 protein expression in human induced pluripotent stem cells, transfected with miRNA mimics or inhibitors. Thereby, we observed that miR‐34a increases TASK‐1 expression and current and further decreases the resting membrane potential of Xenopus laevis oocytes, heterologously expressing hTASK‐1. Finally, we investigated associations between miRNA expression in atrial tissues and clinical parameters of our patient cohort. A cluster containing AF stage, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, left atrial diameter, atrial COL1A2 (collagen alpha‐2(I) chain), and TASK‐1 protein level was associated with increased expression of miR‐25, miR‐21, miR‐34a, miR‐23a, miR‐124, miR‐1, and miR‐29b as well as decreased expression of miR‐9 and miR‐485. Conclusions These results suggest an important pathophysiological involvement of miRNAs in the regulation of atrial expression of the TASK‐1 potassium channel in patients with atrial cardiomyopathy.

Introduction Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes.Methods and analysis The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites.Ethics and dissemination Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results.Trial registration number NCT04347629.

The Late Nordic Iron Age (AD 550-1050) was characterised by significant change in political, military, judicial and religious structures across Scandinavia, most clearly manifested in the appearance of high-status 'central places' in the landscape. Recent ground-penetrating radar surveys at Gjellestad in Norway have revealed a site comprising several large burial mounds--one of which contains a ship burial--in addition to a possible cult house and a feasting hall. This combination of features suggests that Gjellestad was part of a hitherto unknown central place on the eastern shores of the Oslofjord. If correct, the authors' interpretations demonstrate that the layouts of these sites were formulaic, and that central places may be more common than previously thought. Keywords: Scandinavia, Iron Age, Viking Age, central places, ship burial, hall buildings, Introduction The Jell Mound at Gjellestad in Ostfold, Norway, ranks as one of the largest Iron Age funerary monuments in Scandinavia. Standing in isolation on the surrounding low-lying plain, a [...]

Cochlear implants are well established to treat severe hearing impairments. Despite many different approaches to reduce the formation of connective tissue after electrode insertion and to keep electrical impedances low, results are not yet satisfying. Therefore, the aim of the current study was to combine the incorporation of 5% dexamethasone in the silicone body of the electrode array with an additional polymeric coating releasing diclofenac or the immunophilin inhibitor MM284, some anti-inflammatory substances not yet tested in the inner ear. Guinea pigs were implanted for four weeks and hearing thresholds were determined before implantation and after the observation time. Impedances were monitored over time and, finally, connective tissue and the survival of spiral ganglion neurons (SGNs) were quantified. Impedances increased in all groups to a similar extent but this increase was delayed in the groups with an additional release of diclofenac or MM284. Using Poly-L-lactide (PLLA)-coated electrodes, the damage caused during insertion was much higher than without the coating. Only in these groups, connective tissue could extend to the apex of the cochlea. Despite this, numbers of SGNs were only reduced in PLLA and PLLA plus diclofenac groups. Even though the polymeric coating was not flexible enough, MM284 seems to especially have potential for further evaluation in connection with cochlear implantation.

Gang Fang,1 Stacy Cooper Bailey,2 Izabela E Annis,1 Michael K Paasche-Orlow,3 Michael S Wolf,2 Laurie T Martin,4 Michael Emch,5 M Alan Brookhart,6 Karen B Farris7 1Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Division of General Internal Medicine & Geriatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 3Section of General Internal Medicine, Boston University School of Medicine, Boston, MA, USA; 4RAND Corporation, Arlington, VA, USA; 5Department of Geography and Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; 6Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; 7College of Pharmacy, The University of Michigan, Ann Arbor, MI, USACorrespondence: Gang FangDivision of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 2202, Kerr Hall, Chapel Hill, NC 27599-7573, USATel +1 919-966-7517Fax +1 919-966-8486Email gang_fang@unc.eduPurpose: Individual measures of health literacy are not feasible for administration on a large scale, yet estimates of community-level health literacy in the US recently became available. We sought to investigate whether community-level health literacy estimates are associated with the initiation of oral antihyperglycemic agents (OHA) and the use of standard preventive care services among older adults with newly diagnosed diabetes.Patients and methods: We conducted a retrospective cohort study of 169,758 patients, ≥65 years old with hypertension and newly diagnosed type 2 diabetes using 2007–2011 data from the Center for Medicare and Medicaid Services Chronic Conditions Warehouse. We examined the relationship between community-level health literacy estimates and initiation of OHA, receipt of flu shots, eye exams, Hemoglobin A1c tests, and lipid tests within 12 months post diabetes diagnosis.Results: Patients living in communities with above basic health literacy (vs. basic/below basic) were 15% more likely to initiate OHA (Hazard Ratio=1.15; 95% CI 1.12 to 1.18). After classifying the health literacy distribution as quintiles, the analysis revealed a dose–response relationship with OHA initiation that plateaued at the third and fourth quintiles and declined at the fifth quintile. Individuals residing in communities with higher health literacy were more likely to participate in preventive care services (relative risk ranged from 1.09 for lipid test [95% CI 1.07–1.11] to 1.43 for flu shot [95% CI 1.41–1.46]).Conclusion: Community-level health literacy estimates were associated with the initiation of OHA and uptake of standard preventive care services in older adults. Community-level health literacy may help to inform targeted diabetes education and support efforts.Keywords: health literacy, diabetes mellitus, adherence, preventive care

The Eustachian tube (ET) is a bottleneck when it comes to middle ear (ME) health. If its function is impaired, this can lead to serious consequences for the patient, such as hearing problems or deafness. Therefore, this study investigated a tapered nitinol stent (3–5 mm × 14 mm) for the human ET as a potential new permanent treatment for chronic Eustachian tube dysfunction (ETD) and thus ME ventilation disorders. The self-expanding stent was inserted unilaterally into the ET of 24 sheep with observation periods of 3, 6, and 12 months. Local tissue effects and the safety of the stent insertion were analyzed based on regular endoscopic checks, weekly tympanometry measurements, final imaging, and histological examinations. The animals showed no stent-related health restrictions. However, the individual anatomy and stenting procedure had an influence on the results. The tissue reaction in the endoscopic examinations was mild even though no concomitant antibiotics were administered. After all three monitoring periods, stented ETs had a significantly larger ET lumen than the non-stented contralateral ETs. However, tissue growth was detected in the stent. Overall, the first long-term study on an ET stent showed that the tapered ET stent could be a promising treatment option for ETD. [ABSTRACT FROM AUTHOR]

Positional plagiocephaly is a deformational cranial flattening frequently treated in pediatric neurosurgical practice. Positional maneuvers and orthotic helmet therapy are preferred therapeutic options for moderate-to-severe forms. Treatment response seems to be age-dependent. Nevertheless, predictive data are vague, and cost-efficiency might be a limiting factor for treatment. The purpose of this study was to investigate the early predictive value of sonographic parameters on the efficacy of orthotic helmet therapy through the assessment of changes in skull shape and correlation of the parameters with caliper cephalometry values and with age. A consecutive cohort of 49 patients < 10 months of age, undergoing orthotic helmet therapy for positional plagiocephaly, was recruited prospectively. The authors routinely assessed the patency of the lambdoid sutures by ultrasound and the following additional skull parameters were measured: suture width, adjacent full bone thickness, adjacent cortical bone thickness and occipital angle. Caliper cephalometric values, as well as demographic and clinical data were collected. Retrospective data analysis showed an inverse relation between both cortical and full skull bone thickness and early treatment efficacy, defined by a reduction in the occipital angle. The improvement of sonographic parameters correlated with the development of cranial caliper cephalometry values. In conclusion, the sonographic assessment of skull bone thickness is a safe and cost-effective tool to predict the early efficacy of orthotic helmet therapy in positional plagiocephaly and might, therefore, help the clinician to foresee the potential evolution of the deformity. [ABSTRACT FROM AUTHOR]

Abstract Background The Hospital Value Based Purchasing Program (HVBP) in the United States, announced in 2010 and implemented since 2013 by the Centers for Medicare and Medicaid Services (CMS), introduced payment penalties and bonuses based on hospital performance on patient 30-day mortality and other indicators. Evidence on the impact of this program is limited and reliant on the choice of program-exempt hospitals as controls. As program-exempt hospitals may have systematic differences with program-participating hospitals, in this study we used an alternative approach wherein program-participating hospitals are stratified by their financial exposure to penalty, and examined changes in hospital performance on 30-day mortality between hospitals with high vs. low financial exposure to penalty. Methods Our study examined all hospitals reimbursed through the Medicare Inpatient Prospective Payment System (IPPS) – which include most community and tertiary acute care hospitals – from 2009 to 2016. A hospital’s financial exposure to HVBP penalties was measured by the share of its annual aggregate inpatient days provided to Medicare patients (“Medicare bed share”). The main outcome measures were annual hospital-level 30-day risk-adjusted mortality rates for acute myocardial infarction (AMI), heart failure (HF) and pneumonia patients. Using difference-in-differences models we estimated the change in the outcomes in high vs. low Medicare bed share hospitals following HVBP. Results In the study cohort of 1902 US hospitals, average Medicare bed share was 61 and 41% in high (n = 540) and low (n = 1362) Medicare bed share hospitals, respectively. High Medicare bed share hospitals were more likely to have smaller bed size and less likely to be teaching hospitals, but ownership type was similar among both Medicare bed share groups.. Among low Medicare bed share (control) hospitals, baseline (pre-HVBP) 30-day mortality was 16.0% (AMI), 10.9% (HF) and 11.4% (pneumonia). In both high and low Medicare bed share hospitals 30-day mortality experienced a secular decrease for AMI, increase for HF and pneumonia; differences in the pre-post change between the two hospital groups were small (

The Eustachian tube (ET) has a key role in the pathogenesis of otitis media. Until now, there has been a lack of meaningful imaging methods to investigate the ET and its surrounding tissue. The aim of the current study was to investigate the possibilities of imaging the ET using Intravascular Ultrasonography (IVUS). ETs from sheep were scanned ex vivo and in vivo with different IVUS probes. In addition to native ETs, water was also used to improve coupling. Scans were subsequently compared with histological sections and a 3D model of the ET. In addition, ETs with a stenosis induced by a hyaluronic acid depot, after stent insertion, and during lower jaw movement were examined. The IVUS catheter was inserted into the ET lumen without any problems or injuries in all cases. The surrounding structures of the ET were identified in the ultrasound image. In addition, a change in size of the ET lumen due to movement was observed, and the position of the stent and the depot of hyaluronic acid could be examined. With the use of IVUS, a non-invasive possibility to examine the ET over its course with the adjacent structures as well as after different treatments is presented.

Background. When stakeholders offer divergent input, it can be unclear how to prioritize information for decision aids (DAs) on mammography screening. Objectives. This analysis triangulates perspectives (breast cancer screening experts, primary care providers [PCPs], and patients with limited health literacy [LHL]) to understand areas of divergent and convergent input across stakeholder groups in developing a breast cancer screening DA for younger women with LHL. Design. A modified online Delphi panel of 8 experts rated 57 statements for inclusion in a breast cancer screening DA over three rounds. Individual interviews with 25 patients with LHL and 20 PCPs from a large safety net hospital explored informational needs about mammography decision making. Codes from the qualitative interviews and open-ended responses from the Delphi process were mapped across stakeholders to ascertain areas where stakeholder preferences converged or diverged. Results. Four themes regarding informational needs were identified regarding 1) the benefits and harms of screening, 2) different screening modalities, 3) the experience of mammography, and 4) communication about breast cancer risk. Patients viewed pain as the primary harm, while PCPs and experts emphasized the harm of false positives. Patients, but not PCPs or experts, felt that information about the process of getting a mammogram was important. PCPs believed that mammography was the only evidence-based screening modality, while patients believed breast self-exam was also important for screening. All stakeholders described incorporating personal risk information as important. Limitations. As participants came from one hospital, perceptions may reflect local practices. The Delphi sample size was small. Conclusions. Patients, experts, and PCPs had divergent views on the most important information needed for screening decisions. More evidence is needed to guide integration of multiple stakeholder perspectives into the content of DAs. Article Highlights This study combines data from patients with limited health literacy, primary care providers (PCPs), and experts to examine priorities for information inclusion in a breast cancer screening decision aid. All stakeholders described including personal risk information as important. While experts and PCPs prioritized providing evidence-based screening options only, emphasized false positives as the primary mammography harm, and downplayed the relevance of delivering mammography process information, patients had a broader scope of harms (e.g., pain), wanted more information on breast self- exam, and viewed process information as fundamental to their decision making. This study demonstrates that there are differences in what doctors and experts prioritize communicating about breast cancer screening and what patients want to learn about.

Borre in Norway is famous for its Late Nordic Iron and Viking Age (AD 400-1050) monumental burial mounds. Recently, ground-penetrating radar (GPR) surveys have revealed three large structures close to the mound cemetery. Their unusual layout and size, and location within such a prominent burial site, suggest that they were halls--high-status buildings mentioned in the Nordic sagas. The authors present the GPR results, discuss the buildings' typological classification and provide a preliminary chronological framework. The latter suggests that the buildings coexisted with some of the burial mounds, and raises important questions about the significance of such buildings in Nordic moundbuilding societies. Keywords: Norway, Borre, Nordic Iron Age, Viking Age, hall buildings, geophysical survey, Introduction The site of Borre in Norway has captivated historians and archaeologists since the eighteenth century (Figure 1; Nicolaysen 1854; Bragger 1916; Blindheim 1954; Myhre 1992, 2015; 0stigard & Gansum [...]

Background: Users of American Sign Language (ASL) who are deaf often face barriers receiving health information, contributing to significant gaps in health knowledge and health literacy. To reduce the spread of coronavirus disease 2019 (COVID-19) and its risk to the public, the government and health care providers have encouraged social distancing, use of face masks, hand hygiene, and quarantines. Unfortunately, COVID-19 information has rarely been available in ASL, which puts the deaf community at a disadvantage for accessing reliable COVID-19 information. Objective: This study's primary objective was to compare COVID-19–related information access between participants who are deaf and participants who are hearing. Methods: The study included 104 adults who are deaf and 74 adults who are hearing who had participated in a prior health literacy study. Surveys were conducted between April and July 2020 via video conference, smartphone apps, or phone calls. COVID-19 data were linked with preexisting data on demographic and health literacy data as measured by the Newest Vital Sign (NVS) and the ASL-NVS. Key Results: Neither group of participants differed in their ability to identify COVID-19 symptoms. Adults who are deaf were 4.7 times more likely to report difficulty accessing COVID-19 information (p = .011), yet reported using more preventive strategies overall. Simultaneously, adults who are deaf had 60% lower odds of staying home and calling their doctor versus seeking health care immediately or doing something else compared with participants who are hearing if they suspected that they had COVID-19 (p = .020). Conclusions: Additional education on recommended COVID-19 management and guidance on accessible health care navigation strategies are needed for the deaf community and health care providers. Public health officials should ensure that public service announcements are accessible to all audiences and should connect with trusted agents within the deaf community to help disseminate health information online in ASL through their social media channels. [HLRP: Health Literacy Research and Practice. 2021;5(2):e162–e170.] Plain Language Summary: Compared to participants who are hearing, a higher portion of participants who are deaf reported challenges with accessing, understanding, and trusting COVID-19 information. Although respondents who are deaf had similar knowledge of symptoms compared to participants who are hearing, they used more prevention strategies and were more likely to plan immediate care for suspected symptoms. Improved guidance on COVID-19 management and health care navigation accessible to the deaf community is needed.

The Borre Monitoring Project investigated how environmental factors, in particular, precipitation and soil moisture variation as well as different soil and sediment types, affect the quality of GPR data collected for archaeological purposes. To study these questions, regular GPR surveys were conducted over a period of 14 months across a test area covering a hall building at the Iron and Viking Age site of Borre in Norway. In order to obtain in situ measurements of environmental factors relevant for electromagnetic wave propagation including volumetric water content, bulk electrical conductivity, ground temperature, and precipitation, three monitoring stations were erected at the test site. Soil and sediment samples taken from the profiles at the respective monitoring stations were analysed to gain a basic description of their physical and chemical properties. Twelve GPR surveys were conducted roughly once a month between August 2016 and September 2017 and the results clearly indicated differences in the quality of the data collected. To better understand the underlying causes for this variation, GPR data were compared against and integrated with the in situ measurements gathered using the monitoring stations. The results of this analysis emphasised the benefit of dry conditions, which, if prevailing over a longer period of time, proved to generate GPR data of the highest quality. Seasonality could not be attested; instead, data quality was governed by small-scale weather patterns, where the time and intensity of rainfall events prior to the surveys as well as sudden changes in air temperature played a decisive role. While the results of this study are only valid for sites with similar settings such as Borre, they emphasise the importance of considering the environmental factors during all stages of a GPR survey and highlight the need for further studies investigating other settings.

Otitis media is often connected to Eustachian tube dysfunction (ETD). Until now, there was no large animal model available for the examination of new treatment methods such as stents for the Eustachian tube (ET). Thus, the aim of the study was to develop a method to reproducibly induce ETD by injection of fillers and without permanent closure of the ET. Tools for safe injection of hyaluronic acid (HA) in the surrounding of the ET were developed. In ex vivo experiments, HA mixed with Imeron® was injected close to the nasopharyngeal orifice of the ET of blackface sheep. The established depot was visualized using cone beam computer tomography and magnetic resonance imaging, and stents could be placed into the ET. A reliable position of the HA depot was achieved. This method was transferred to in vivo, and middle ear ventilation was investigated by tympanometry. ETD was achieved with amounts of 2.5 mL HA or higher. None of the animals showed any sign of discomfort or complications. The induced ETD lasted for 3 to 13 (maximum observation period) weeks and was also combined with middle ear effusion. A model of ETD based on injection of HA next to the ET was successfully established and is now available to test novel treatment options for ET functionality.

ObjectivesTo examine the effect of the relationship between literacy and other individual-level factors on having an advance directive (AD).DesignFace-to-face structured interview.SettingParticipants were recruited from an academic general internal medicine clinic and one of four federally qualified health centers in Chicago.ParticipantsSeven hundred eighty-four adults aged 55 to 74.MeasurementsAssessment of participant literacy, sociodemographic factors, and having an AD for medical care.ResultsOne-eighth (12.4%) of participants with low literacy, 26.6% of those with marginal literacy, and 49.5% of those with adequate literacy reported having an AD (P

Introduction Predialysis education for patients with advanced chronic kidney disease (CKD) typically focuses narrowly on haemodialysis and peritoneal dialysis as future treatment options. However, patients who are older or seriously ill may not want to pursue dialysis and/or may not benefit from this treatment. Conservative kidney management, a reasonable alternative treatment, and advance care planning (ACP) are often left out of patient education and shared decision-making. In this study, we will pilot an educational intervention (Conservative Kidney Management Options and Advance Care Planning Education—COPE) to improve knowledge of conservative kidney management and ACP among patients with advanced CKD who are older and/or have poor functional status.Methods and analysis This is a single-centre pilot randomised controlled trial at an academic centre in Philadelphia, PA. Eligible patients will have: age ≥70 years and/or poor functional status (as defined by Karnofsky Performance Index Score

Chronic infections are often connected to biofilm formation. In presence of implants, this can lead to loss of the implant. Systemic or local application of drugs is relatively ineffective in case of biofilm formation. One technique to provide antibacterial properties on demand is the antibacterial photodynamic therapy (aPDT). Using this technique, these properties can be "switched on" by light illumination. In the middle ear with the semitransparent tympanic membrane, it might be possible in future to activate the antibacterial effect without opening the membrane. Therefore, we investigated the optical absorbance spectra of the tympanic membrane. Optical absorbance spectra were measured in ex vivo preparations from neonatal and adult rats with the membrane still being attached to the surrounding bony ring and four human samples. After performing area scans, the spot with the lowest absorbance being surrounded by a ring like structure with higher absorbance was chosen as region of interest for scanning wavelengths between 300 and 900 nm. Absorbance is generally higher at lower wavelengths with a local absorbance maximum at 420 nm and a weak second maximum with two neighbouring peaks at 540 / 580 nm and is significantly higher in adult rats compared to neonatal rats where about 10% of light was transmitted. The human samples show similar characteristics with a little higher absorbance. For activation of aPDT through the tympanic membrane, larger wavelengths are more promising. Whether the amount of light transmitted through the membrane would be sufficient to induce aPDT remains to be tested in further experiments.

The extent of dysfunction of the Eustachian tube (ET) is relevant in understanding the pathogenesis of secondary otological diseases such as acute or chronic otitis media. The underlying mechanism of ET dysfunction remains poorly understood except for an apparent genesis such as a nasopharyngeal tumor or cleft palate. To better describe the ET, its functional anatomy, and the biomechanical valve mechanism and subsequent development of diagnostic and interventional tools, a three-dimensional model based on thin-layer histology was created from an ET in this study. Blackface sheep was chosen as a donor. The 3-D model was generated by the coherent alignment of the sections. It was then compared with the cone-beam computed tomography dataset of the complete embedded specimen taken before slicing. The model shows the topographic relation of the individual components, such as the bone and cartilage, the muscles and connective tissue, as well as the lining epithelium with the lumen. It indicates a limited spiraling rotation of the cartilaginous tube over its length and relevant positional relationships of the tensor and levator veli palatine muscles.