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Background: RBPs (RNA-binding proteins) perform indispensable functions in the post-transcriptional regulation of gene expression. Numerous RBPs have been implicated in cardiac development or physiology based on gene knockout studies and the identification of pathogenic RBP gene mutations in monogenic heart disorders. The discovery and characterization of additional RBPs performing indispensable functions in the heart will advance basic and translational cardiovascular research. Methods: We performed a differential expression screen in zebrafish embryos to identify genes enriched in nkx2.5 -positive cardiomyocytes or cardiopharyngeal progenitors compared to nkx2.5 -negative cells from the same embryos. We investigated the myocardial-enriched gene RNA-binding protein with multiple splicing (variants) 2 [ RBPMS2 )] by generating and characterizing rbpms2 knockout zebrafish and human cardiomyocytes derived from RBPMS2 -deficient induced pluripotent stem cells. Results: We identified 1848 genes enriched in the nkx2.5 -positive population. Among the most highly enriched genes, most with well-established functions in the heart, we discovered the ohnologs rbpms2a and rbpms2b , which encode an evolutionarily conserved RBP. Rbpms2 localizes selectively to cardiomyocytes during zebrafish heart development and strong cardiomyocyte expression persists into adulthood. Rbpms2-deficient embryos suffer from early cardiac dysfunction characterized by reduced ejection fraction. The functional deficit is accompanied by myofibril disarray, altered calcium handling, and differential alternative splicing events in mutant cardiomyocytes. These phenotypes are also observed in RBPMS2-deficient human cardiomyocytes, indicative of conserved molecular and cellular function. RNA-sequencing and comparative analysis of genes mis-spliced in RBPMS2-deficient zebrafish and human cardiomyocytes uncovered a conserved network of 29 ortholog pairs that require RBPMS2 for alternative splicing regulation, including RBFOX2, SLC8A1 , and MYBPC3 . Conclusions: Our study identifies RBPMS2 as a conserved regulator of alternative splicing, myofibrillar organization, and calcium handling in zebrafish and human cardiomyocytes.

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium‐based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast‐enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. Methods and Results Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed to assess myocardial lesion burden using both contrast agents. Late gadolinium enhancement cardiac magnetic resonance imaging was examined 10 and 15 minutes after contrast injection. Contrast agents were administered in alternating manner with a 2‐ to 3‐hour washout period between contrast agent injections. Lesion evaluation and image processing were performed using Segment Medviso software. Mean infarct size and transmurality, measured using RVP‐001, were not different compared with those measured using late gadolinium enhancement images. Bland‐Altman analysis demonstrated a nominal bias of 0.13 mL ( Conclusions The experimental manganese‐based contrast agent RVP‐001 appears to be an effective agent for assessment of myocardial infarction location, size, and transmurality, and it may be useful as an alternative to gadolinium‐based agents.

Objectives Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. Design The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. Methods Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed). Results Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred. Conclusion These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [ClinicalTrials.gov, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results), http://links.lww.com/QAD/C189].

Objective: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp +/− mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident HFpEF. Aortic PWV was increased in older, but not young, female Mgp +/− mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. Conclusions: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future HFpEF in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in HFpEF.

Background: Previous data from NHANES 1999-2004 showed that women aged 45-54 years were more than twice as likely as men to report a prior stroke. Little is known about recent sex-specific trends in midlife stroke prevalence and risk factors for stroke. Methods: We assessed age- and sex- specific trends in stroke prevalence among individuals aged 35-64 years (n= 23,936; weighted n= 349,074,769) participating in NHANES across epochs in 6-year intervals (1999-2004, 2005-2010, 2011-2016) using survey weighted counts and proportions to reflect US national estimates. Stroke was self-reported. Survey adjusted logistic regression models compared odds of prior stroke by sex across time for each midlife decade adjusting for sociodemographic and clinical variables. Trends in prevalence of vascular risk factors were assessed over time. Results: In 1999-2004, women aged 45-54 years were over twice as likely as men to report prior stroke (OR 2.4, 95% CI 1.4-4.2, p=0.002). In 2005-2010 and 2011-2016, the differences were no longer significant (OR 1.5, 0.9-2.5, p=0.15 and OR 0.9, 0.5-1.6, p=0.71). There were no sex differences in stroke prevalence for those aged 35-44 and 55-64 years (Table). Among those aged 45-54 years, mean systolic blood pressure (SBP) were comparable between women and men in 1999-2004 (124, SE 0.7 mmHg vs 125, SE 0.6 mmHg, p= 0.27), but women’s mean SBP decreased to 121, SE 0.6 mmHg in 2011-2016, while men’s remained stable at 124, SE 0.6 mmHg. Diabetes prevalence increased in both men (9% to 13%) and women (8% to 10%). Obesity prevalence increased from 31% to 38% in men and 37% to 42% in women. Conclusion: A decade later the midlife stroke prevalence surge among women (vs. men) in the US has abated. However, it is unclear whether this change is due to shifts in incidence or case fatality and opportunities remain to address cardiometabolic risk factors for both sexes.

INTRODUCTION AND OBJECTIVE:Partial-gland high intensity focused ultrasound (HIFU) requires accurate localization of cancer within the prostate. We conducted a pilot trial to determine if a novel hi...

INTRODUCTION: The COVID-19 pandemic has led to widespread disruptions of outpatient endoscopic procedures The Division of Gastroenterology and Hepatology at UTMB developed a tiered strategy for risk stratifying pandemic-related cancellations, in an effort to systematically reschedule patients The Centers for Medicare and Medicaid Services, in concordance with multi- society guidelines, provided a framework for gradual reopening of outpatient procedures Here we describe the process and outcomes of the tier-based reinstitution of our outpatient endoscopy after flattening of the COVID-19 curve to provide urgent endoscopy services within a reasonable period applying appropriate risk mitigation precautions METHODS: Patients with pandemic-related cancellations from 3/16/2020 to 4/20/2020 were stratified into tier groups (1-4) in order of urgency (Table 1) During phase 1 of Texas's reopening, tiers 1 (urgent/emergent) and 2 (semi-urgent) were rescheduled within 1 and 4 weeks, respectively During phase 2, tiers 3 and 4 were subsequently rescheduled within 3 months Additional measures taken between phase 1 and 2 included pre-procedural testing of all inpatient and outpatients, employee testing, symptom screenings, surgical mask use, and internal social distancing Patients who chose not to reschedule were asked to provide their rationale (Table 2) RESULTS: Of the 540 patients awaiting delayed procedures, 14/16 (87 50%) patients in tier 1 and 147/170 (86 47%) patients in tier 2 could be contacted by phone to discuss the possibility for scheduling Of these, only 57 14% of tier 1 and 48 97% of tier 2 could be scheduled at their goal procedure interval Despite counseling on the safety measures instituted, the most commonly identified barrier for rescheduling urgent or semi-urgent endoscopy was COVID-19 related concerns in 40% Reassuringly, our pre-procedure COVID testing of the patients willing to return for their procedures revealed an incidence of 1 3%, as compared to 4 4% in Galveston county CONCLUSION: Our model describes a tier-based system that can be used to safely reintroduce elective procedures prioritized based on urgency The majority of patients across all tiers were rescheduled within 4 weeks We plan to contact patients 2 weeks after endoscopy to inquire about COVID-19 testing and results, which will allow us to evaluate the efficacy of our peri-procedural transmission prevention measures

Background and Purpose— Early diagnosis of cerebral venous thrombosis (CVT) is currently a major clinical challenge. We proposed a novel magnetic resonance black-blood thrombus imaging technique (MRBTI) for detection and quantification of CVT. Methods— MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into 2 groups based on the duration of clinical onset: ≤7 days (group 1) and between 7 and 30 days (group 2). Signal/noise ratio was calculated for the detected thrombus, and contrast/noise ratio was measured between thrombus and lumen and also between thrombus and brain tissue. The feasibility of using MRBTI for thrombus volume measurement was explored, and total thrombus volume was calculated for each patient. Results— In 23 patients with proven CVT, MRBTI correctly identified 113 of 116 segments with a sensitivity of 97.4%. Thrombus signal/noise ratio was 153±57 and 261±95 for group 1 (n=10) and group 2 (n=13), respectively ( P P Conclusions— The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first-line diagnostic imaging tool.

Acute lower gastrointestinal (GI) bleeding is self-limiting and managed conservatively. Ongoing bleeding from a lower GI source and hemodynamic instability can create difficult diagnostic and therapeutic dilemmas. The severity of bleeding can necessitate emergent diagnostic and therapeutic interventions. Diverticulosis and angiodysplasias are the most common causes of massive lower GI hemorrhage. Other etiologies that can lead to life-threatening hemorrhage are important to recognize. We present a rare case of massive lower GI hemorrhage attributable to a superior rectal artery pseudoaneurysm. The absence of a preceding traumatic or iatrogenic cause distinguishes this case from other reports in the literature.

Supplemental Digital Content is available in the text., Background— The objective of this study is to assess the dynamic alterations of myocardial microstructure and strain between diastole and systole in patients with dilated cardiomyopathy relative to healthy controls using the magnetic resonance diffusion tensor imaging, myocardial tagging, and biomechanical modeling. Methods and Results— Dual heart-phase diffusion tensor imaging was successfully performed in 9 patients and 9 controls. Tagging data were acquired for the diffusion tensor strain correction and cardiac motion analysis. Mean diffusivity, fractional anisotropy, and myocyte aggregate orientations were compared between both cohorts. Cardiac function was assessed by left ventricular ejection fraction, torsion, and strain. Computational modeling was used to study the impact of cardiac shape on fiber reorientation and how fiber orientations affect strain. In patients with dilated cardiomyopathy, a more longitudinal orientation of diastolic myofiber aggregates was measured compared with controls. Although a significant steepening of helix angles (HAs) during contraction was found in the controls, consistent change in HAs during contraction was absent in patients. Left ventricular ejection fraction, cardiac torsion, and strain were significantly lower in the patients compared with controls. Computational modeling revealed that the dilated heart results in reduced HA changes compared with a normal heart. Reduced torsion was found to be exacerbated by steeper HAs. Conclusions— Diffusion tensor imaging revealed reduced reorientation of myofiber aggregates during cardiac contraction in patients with dilated cardiomyopathy relative to controls. Left ventricular remodeling seems to be an important factor in the changes to myocyte orientation. Steeper HAs are coupled with a worsening in strain and torsion. Overall, the findings provide new insights into the structural alterations in patients with dilated cardiomyopathy.

Body core cooling via the palm of a hand increases work volume during resistive exercise. We asked: (a) "Is there a correlation between elevated core temperatures and fatigue onset during resistive exercise?" and (b) "Does palm cooling between sets of resistive exercise affect strength and work volume training responses?" Core temperature was manipulated by 30-45 minutes of fixed load and duration treadmill exercise in the heat with or without palm cooling. Work volume was then assessed by 4 sets of fixed load bench press exercises. Core temperatures were reduced and work volumes increased after palm cooling (Control: Tes = 39.0 ± 0.1° C, 36 ± 7 reps vs. Cooling: Tes = 38.4 ± 0.2° C, 42 ± 7 reps, mean ± SD, n = 8, p < 0.001). In separate experiments, the impact of palm cooling on work volume and strength training responses were assessed. The participants completed biweekly bench press or pull-up exercises for multiple successive weeks. Palm cooling was applied for 3 minutes between sets of exercise. Over 3 weeks of bench press training, palm cooling increased work volume by 40% (vs. 13% with no treatment; n = 8, p < 0.05). Over 6 weeks of pull-up training, palm cooling increased work volume by 144% in pull-up experienced subjects (vs. 5% over 2 weeks with no treatment; n = 7, p < 0.001) and by 80% in pull-up naive subjects (vs. 20% with no treatment; n = 11, p < 0.01). Strength (1 repetition maximum) increased 22% over 10 weeks of pyramid bench press training (4 weeks with no treatment followed by 6 weeks with palm cooling; n = 10, p < 0.001). These results verify previous observations about the effects of palm cooling on work volume, demonstrate a link between core temperature and fatigue onset during resistive exercise, and suggest a novel means for improving strength and work volume training responses.

Introduction: Field transmission of pre-hospital ECG images to facilitate advance activation of the STEMI system of care has been shown to be effective in improving patient care and prognosis. Current commercial wireless ECG transmission systems available are effective, but are expensive to implement and maintain. Head to head testing was performed using an iPhone application to mediate ECG image transmission on three national cellular carriers in comparison to one commercial ECG transmission system. This resulted in comparable performance particularly in signal rich coverage environments contained three or greater bars. Hypothesis: An iPhone application that mediates pre-hospital ECG image transmission could be a cost effective alternative to current commercial systems incorporated in the pre-hospital STEMI system of care. Using a mobile phone signal booster could enhance application performance to consistently transmit in all signal coverage environments. Testing: The application was tested on three national cellular carriers with two commercial systems. Data was collected with and without the addition of the mobile phone signal booster at 75 waypoints covering the entire signal coverage environment. Application performance was determined by the average percentage of successful transmission and duration of transmission within the total signal coverage environment. Results: As shown in Figure 1, using the mobile phone signal booster resulted in marked improvements to successful transmission. Performance of the carriers under boosted conditions was merged, as the differences were not statistically significant enough to warrant differentiation. Within the signal-limited environment, the application displayed superior reliability to the two commercial systems, while in the signal rich environment it was comparable. Minimal improvement was also seen in the duration of transmission of the application, although it was more apparent within the signal limited environment than in the signal rich environment. Conclusion: The addition of the mobile phone signal booster enhances the performance of the iPhone application, allowing it to successfully transmit ECGs more consistently than commercial systems in all signal coverage environments.

that might identify these lesions for targeting. However, although identifiable on MRI, anterior lesions show an overlap in appearance between adenomas and tumors making the diagnosis challenging. It is necessary to identify morphological and quantitative characteristics on multi-parametric MRI to help distinguish adenomas from cancer. METHODS: 56 consecutive patients (2007-2011) who underwent multi-parametric MRI for assessment of prostate cancer and which showed a suspicious lesion in the transition zone (TZ) were evaluated. MRIs were 1.5T using a pelvic phased array coil and T2, dynamic contrast-enhancement and diffusionâV“weighting (ADC and dedicated b1⁄41400). All cases had targeted sampling of the lesion. Significant tumor was defined as a cancer core length of >/1⁄44mm and/or any Gleason grade 4 component within the MRI area of suspicion. PZ and TZ were separately scored from 1 (tumor very unlikely) to 5 (tumor very likely). The volume, relationship to the anterior fibromuscular stroma (AFMS), contrast and diffusion signal intensity and signal homogeneity were assessed. RESULTS: First, the presence on a pseudo-capsule and the lack of AFMS abutment were strongly associated with benign lesions. If this were taken into account, 48% and 52% of false positives in the TZ could have been avoided. Second, a high signal on the B1⁄41400 diffusion images, homogeneous T2 signal and homogeneous contrastenhancment were associated with cancer. CONCLUSIONS: We have identified a number of mp-MRI features that can aid the differentiation between cancer and benign tissue in the difficult-to-interpret anterior prostate that will be useful for interpreting MR-images to further improve diagnostic accuracy.