Global longitudinal strain and biomarkers of cardiac damage and stress as predictors of outcomes after transcatheter aortic valve implantation

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction \u3c50% was observed in 19% and impaired GLS (aGLS \u3c15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively

Metabolic signatures of cardiac dysfunction, multimorbidity, and post-transcatheter aortic valve implantation death

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]

Bioresponsive polymers for nanomedicine: expectations and reality!

Bioresponsive polymers in nanomedicine have been widely perceived to selectively activate the therapeutic function of nanomedicine at diseased or pathological sites, while sparing their healthy counterparts. This idea can be described as an advanced version of Paul Ehrlich's magic bullet concept. From that perspective, the inherent anomalies or malfunction of the pathological sites are generally targeted to allow the selective activation or sensory function of nanomedicine. Nonetheless, while the primary goals and expectations in developing bioresponsive polymers are to elicit exclusive selectivity of therapeutic action at diseased sites, this remains difficult to achieve in practice. Numerous research efforts have been undertaken, and are ongoing, to tackle this fine-tuning. This review provides a brief introduction to key stimuli with biological relevance commonly featured in the design of bioresponsive polymers, which serves as a platform for critical discussion, and identifies the gap between expectations and current reality.Drug Delivery Technolog

Evidence for the interaction of Endophilin A3 with endogenous K(Ca)2.3 channels in PC12 cells

Background/Aims: Small-conductance calcium-activated (SK) channels play an important role by controlling the after-hyperpolarization of excitable cells. The level of expression and density of these channels is an essential factor for controlling different cellular functions. Several studies showed a co-localization of KCa2.3 channels and Endophilin A3 in different tissues. Endophilin A3 belongs to a family of BAR- and SH3 domain containing proteins that bind to dynamin and are involved in the process of vesicle scission in clathrin-mediated endocytosis. Methods: Using the yeast two-hybrid system and the GST pull down assay we demonstrated that Endophilin A3 interacts with the N-terminal part of KCa2.3 channels. In addition, we studied the impact of this interaction on channel activity by patch clamp measurements in PC12 cells expressing endogenous KCa2.3 channels. KCa2.3 currents were activated by using pipette solutions containing 1 µM free Ca(2+). Results: Whole-cell measurements of PC12 cells transfected with Endophilin A3 showed a reduction of KCa2.3 specifc Cs(+) currents indicating that the interaction of Endophilin A3 with KCa2.3 channels also occurs in mammalian cells and that this interaction has functional consequences for current flowing through KCa2.3 channels. Since KCa2.3 specific currents could be increased in PC12 cells transfected with Endophilin A3 with DC-EBIO (30 µM), a known SK-channel activator, these data also implicate that Endophilin A3 did not significantly remove KCa2.3 channels from the membrane but changed the sensitivity of the channels to Ca(2+) which could be overcome by DC-EBIO. Conclusion: This interaction seems to be important for the function of KCa2.3 channels and might therefore play a significant role in situations where channel activation is pivotal for cellular function

Cyclotron Resonance in the Layered Perovskite Superconductor Sr2RuO4

We have measured the cyclotron masses in Sr2RuO4 through the observation of periodic-orbit-resonances - a magnetic resonance technique closely related to cyclotron resonance. We obtain values for the alpha, beta and gamma Fermi surfaces of (4.33+/-0.05)me, (5.81+/-0.03)me and (9.71+/-0.11)me respectively. The appreciable differences between these results and those obtained from de Haas- van Alphen measurements are attributable to strong electron-electron interactions in this system. Our findings appear to be consistent with predictions for a strongly interacting Fermi liquid; indeed, semi-quantitative agreement is obtained for the electron pockets beta and gamma.Comment: 4 pages + 3 figure

The treatment of achalasia patients with esophageal varices: an international study

Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller’s myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non- cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation. Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices

Frustrated kinetic energy, the optical sum rule, and the mechanism of superconductivity

The theory that the change of the electronic kinetic energy in a direction perpendicular to the CuO-planes in high-temperature superconductors is a substantial fraction of the condensation energy is examined. It is argued that the consequences of this theory based on a rigorous $c$-axis conductivity sum rule are consistent with recent optical and penetration depth measurements.Comment: 4 pages (RevTeX) and 2 eps figure

Reproductive health related complications of spinal cord injury among patients at a specialized center in Bangladesh

Background: Our objective was to find out the reproductive health related complications among spinal cord injury patients. Methods: A cross sectional study was conducted at the Center for the Rehabilitation of the Paralyzed (CRP) in Savar, Dhaka, Bangladesh from August 2017 to July 2018. A total of 289 patients, both indoor and outdoor, with spinal cord injury were randomly selected. The study aimed to examine reproductive health complications associated with spinal cord injury. Data was collected using a questionnaire and analyzed using SPSS version 20. Results: Among 220 (76.1%) were male and 69 (23.9%) were female. In 15-35 (68.1% and 91.2%), 47 (68.1%) participants had menstruation problem. 42.1% had autonomic dysreflexia and 57.9% had UTI as pregnancy related complications. In sexual activity 52% had difficulties having intercourse, 20% had difficulties to reach orgasm and 28% had dry sex. In male participants after SCI 70.5% had erection problem and 78.6% had ejaculation problem. Participants who had erection problem, most of their neurological level was thoracic level 84.51% and in case of ejaculation also their neurological level was thoracic level 81.50%. Conclusions: Awareness of sexuality and reproductive health after SCI has grown among healthcare professionals and individuals with spinal cord injuries. This recognition emphasizes the importance of open discussions, active listening, and education to enhance the quality of life for those affected by spinal cord injury

Respondent-Driven Sampling in a Study of Drug Users in New York City: Notes from the Field

Beth Israel Medical Center (BIMC), in collaboration with the Centers for Disease Control (CDC) and the New York State Department of Health (NYSDOH), used respondent-driven sampling (RDS) in a study of HIV seroprevalence among drug users in New York City in 2004. We report here on operational issues with RDS including recruitment, coupon distribution, storefront operations, police and community relations, and the overall lessons we learned. Project staff recruited eight seeds from a syringe exchange in Lower Manhattan to serve as the initial study participants. Upon completion of the interview that lasted approximately 1 h and a blood draw, each seed was given three coupons to recruit three drug users into the study. Each of the subsequent eligible participants was also given three coupons to recruit three of their drug-using acquaintances. Eligible participants had to have: injected, smoked or snorted an illicit drug in the last 6 months (other than marijuana), aged 18 or older, adequate English language knowledge to permit informed consent and complete questionnaire. From April to July 2004, 618 drug users were interviewed, including 263 (43%) current injectors, 119 (19%) former injectors, and 236 (38%) never injectors. Four hundred sixty nine (76%) participants were men, 147 (24%) were women, and two (<1%) were transgender. By race/ethnicity, 285 (46%) were black, 218 (35%) Hispanic, 88 (14%) white, 23 (4%) mixed/not specified, and four (<1%) native American. Interviews were initially done on a drop-in basis but this system changed to appointments 1 month into the study due to the large volume of subjects coming in for interviews. Data collection was originally proposed to last for 1 year with a target recruitment of 500 drug users. Utilizing RDS, we were able to recruit and interview 118 more drug users than originally proposed in one quarter of the time. RDS was efficient with respect to time and economics (we did not have to hire an outreach worker) and effective in recruiting a diverse sample of drug users

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

Abstract Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world&apos;s land surface, with the world&apos;s governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species&apos; extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as &apos;important sites&apos;). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with.50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45-1.14% annually since 1950 for IBAs and 0.79-1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends