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Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young people. Although rare genetic variants are well-established contributors to HCM risk, common genetic variants have recently been implicated in disease pathogenesis.

To assess the contributions of rare and common genetic variation to risk of HCM in the general population.

This cohort study of the UK Biobank (data from 2006-2010) and the Mass General Brigham Biobank (2010-2019) assessed the relative and joint contributions of rare genetic variants and a common variant (polygenic) score to risk of HCM. Both rare and common variant predictors were then evaluated in the context of relevant clinical risk factors. Data analysis was conducted from May 2021 to February 2022.

Pathogenic rare variants, common-variant (polygenic) score, and clinical risk factors.

Risk of HCM.

The primary study population comprised 184 511 individuals from the UK Biobank. Mean (SD) age was 56 (8) years, 83 690 (45%) of participants were men, ase) improved the area under the receiver operator characteristic curve from 0.71 (95% CI, 0.65-0.77) to 0.82 (95% CI, 0.77-0.87).

Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.

Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.

To compare cone mosaic metrics derived from adaptive optics scanning light ophthalmoscopy (AOSLO) images with those derived from Heidelberg Engineering SPECTRALIS High Magnification Module (HMM) images.

Participants with contiguous cone mosaics had HMM imaging performed at locations superior and temporal to the fovea. These images were registered and averaged offline and then aligned to split-detection AOSLO images; 200 × 200-µm regions of interest were extracted from both modalities. Cones were semi-automatically identified by two graders to provide estimates of cone density and spacing.

Thirty participants with contiguous cone mosaics were imaged (10 males, 20 females; age range, 11-67 years). Image quality varied, and 80% of our participants had analyzable HMM images. The intergrader intraclass correlation coefficients for cone metrics were good for both modalities (0.688-0.757 for HMM; 0.805-0.836 for AOSLO). Cone density estimates from HMM images were lower by 2661 cones/mm2 (24.1%) on average compared to AOSLO-derived estimates. Accordingly, HMM estimates of cone spacing were increased on average compared to AOSLO.

The cone mosaic can be visualized in vivo using the SPECTRALIS HMM, although image quality is variable and imaging is not successful in every individual. Metrics extracted from HMM images can differ from those from AOSLO, although excellent agreement is possible in individuals with excellent optical quality and precise co-registration between modalities.

Emerging non-adaptive optics-based photoreceptor imaging is more clinically accessible than adaptive optics techniques and has potential to expand high-resolution imaging in a clinical environment.

Emerging non-adaptive optics-based photoreceptor imaging is more clinically accessible than adaptive optics techniques and has potential to expand high-resolution imaging in a clinical environment.

To determine the sensitivity of optical coherence tomography (OCT) and standard automated perimetry (SAP) for detecting glaucomatous progression in the superior and inferior hemiretina.

We calculated contrast-to-noise ratios (CNRs) for OCT retinal nerve fiber layer (RNFL) thickness of hemiretinas and for SAP mean total deviation (MTD) of the corresponding hemifields from longitudinal data (205 eyes, 125 participants). The glaucoma stage for each hemiretina was based on the corresponding hemifield's MTD. Contrast was defined as the difference of the parameter between two consecutive glaucoma stages, whereas noise was the measurement variability of the parameter in those stages. The higher the CNR of a parameter, the more sensitive it is to detecting progression in the transition between successive stages.

There were no statistically significant differences for the RNFL CNR and MTD CNR between superior and inferior hemiretinas. As the glaucoma stage of the opposite hemiretina worsened, the MTD CNR in the transition from moderate to advanced glaucoma significantly increased. The RNFL CNR in the transition from mild to moderate glaucoma significantly decreased in case of advanced glaucoma in the opposite hemiretina.

Similar to full retinas, detecting conversion to glaucoma in hemiretinas is more sensitive with OCT than SAP, whereas with more advanced disease, SAP is more sensitive for detecting progression. More importantly, the sensitivity for detecting progression in one hemiretina with either technique depends on the glaucoma severity in the opposite hemiretina.

Monitoring glaucomatous progression with either OCT or SAP partly depends on the glaucoma severity in the opposite hemiretina.

Monitoring glaucomatous progression with either OCT or SAP partly depends on the glaucoma severity in the opposite hemiretina.

To accurately evaluate pressure changes during vitrectomy in a rigid model of the vitreous chamber and to test the efficiency of the EVA phacovitrectomy system (Dutch Ophthalmic Research Center) in terms of compensation of intraocular pressure variations.

We tested 23-, 25-, and 27-gauge double-blade vitreous cutters in both vented global pressure control and automatic infusion compensation (AIC) modes in a vitreous chamber model, mimicking the real surgical procedure. Balanced salt solution and artificial vitreous, similar to the real vitreous body, were used. We tested both standard-flow (SF) and high-flow (HF) infusion systems, varying the infusion pressure between 20 and 40 mm Hg. In each experiment, flow rate was also measured.

Pressure drop was rapidly and efficiently compensated when 23- and 25-gauge cutters were used in AIC mode, with infusion pressures ranging between 30 and 55 mm Hg. The 27-gauge cutter was less efficient in compensating pressure variations. check details Pressure fluctuations related to the high-frequency motion of the cutter blade were small compared to the overall pressure variations. The use of the HF infusion system resulted in larger flow rates and lower pressure changes compared to the SF infusion system.

Despite the rigid material of the model, the present pressure measurements are in line with previous studies performed on porcine eye. The use of AIC mode compensates intraoperative pressure drops efficiently, with both 23- and 25-gauge cutters. The HF infusion system is more efficient than the SF infusion system.

The AIC infusion mode efficiently compensates intraoperative pressure drops, in both 23- and 25-gauge experimental vitrectomy. The HF infusion system resulted in larger flow rate and lower pressure changes.

The AIC infusion mode efficiently compensates intraoperative pressure drops, in both 23- and 25-gauge experimental vitrectomy. The HF infusion system resulted in larger flow rate and lower pressure changes.

Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.

To use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment.

A retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant wrsisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD] male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD] male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death.

These results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

These results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.This cohort study investigates associations between implementation of the acuity circles liver allocation policy and the timing of donor liver procurements in the US.Proteinase K (PK) is a proteolytic enzyme that has been widely used in nucleic acid purification, leather production, environmental protection, and other industrial applications. However, this biocatalyst cannot tolerate high temperatures which has severely restricted its wider application. As reported in previous studies, cholinium-based ionic liquids (ILs) have gained tremendous attention serving as a promising media to stabilize and preserve proteins, DNA, and other biomolecules due to their environmentally benign nature and biocompatibility. In this work, we chose 13 different kinds of cholinium-based ILs to examine their effects on the thermal stability and enzymatic activity of PK. We found that biocompatible cholinium-based ions with appropriately chosen anions can greatly improve the thermal stability of PK, whose melting temperature (Tm) is increased from ∼74.4 °C to 87.7 °C. However, the enzymatic activity is slightly reduced in the presence of ILs. Further comparison of our results with other literature findings suggests that kosmotropic anions of cholinium-based ILs are crucial to maintain the thermal stability of proteins. However, to achieve the best performance, the choice of IL anions is protein specific.This comparative effectiveness study compares the cure rates of battery-powered electrocautery and curettage vs electrodesiccation and curettage in treating nonmelanoma skin cancer.

Differences in time to diagnostic and therapeutic measures can contribute to disparities in outcomes. However, whether there is an association of timeliness by sex for trauma patients is unknown.

To investigate whether sex-based differences in time to definitive interventions exist for trauma patients in the US and whether these differences are associated with outcomes.

This was a retrospective cohort study conducted from July 2020 to July 2021, using the 2013 to 2016 Trauma Quality Improvement Program (TQIP) databases from level I to III trauma centers in the US. Patients 18 years or older with an Injury Severity Score (ISS) greater than 15 and who carried diagnoses of traumatic brain injury, intra-abdominal injury, pelvic fracture, femur fracture, and spinal injury as a result of their trauma were included in the study. Data were analyzed from July 2020 to July 2021.

Primary outcomes assessed timeliness to interventions, using Wilcoxon signed rank and χ2 tests. Secondary outcomes included location of discharge after injury, using propensity score-matched generalized estimating equations modeling.