Hall effect measurements on strained and unstrained thin films of La0.7Ca0.3MnO3 and La0.7Sr0.3MnO3

205103Quantum Matter and Optic

High-Septal Pacing Reduces Ventricular Electrical Remodeling and Proarrhythmia in Chronic Atrioventricular Block Dogs

ObjectivesThis study was designed to analyze the relevance of ventricular activation patterns for ventricular electrical remodeling after atrioventricular (AV) block in dogs.BackgroundBradycardia is thought to be the main contributor to ventricular electrical remodeling after complete AV block. However, an altered ventricular activation pattern or AV dyssynchrony may also contribute.MethodsFor 4 weeks, AV block dogs were either paced from the high-ventricular septum near the His bundle at lowest captured rate (n = 9, high-septal pacing [HSP]) or kept at idioventricular rate without controlled activation (n = 14, chronic AV block [CAVB]). Multiple electrocardiographic and electrophysiological parameters were measured under anesthesia at 0 and 4 weeks. Proarrhythmia was tested at 4 weeks by IKrblock (25 μg/kg dofetilide intravenous).ResultsAt 0 weeks, the 2 groups were comparable, whereas after 4 weeks of similar bradycardia, QT duration at unpaced conditions had increased from 300 ± 5 to 395 ± 18 ms in CAVB (+32 ± 6%) and from 307 ± 8 ms to 357 ± 11 ms in HSP (+17 ± 4%; p < 0.05). Frequency dependency of repolarization was less steep in HSP compared to CAVB dogs after 4 weeks remodeling. Beat-to-beat variability of repolarization, a proarrhythmic parameter, increased only in CAVB from 0 to 4 weeks. Torsades de pointes arrhythmias were induced at 4 weeks in 44% HSP versus 78% CAVB dogs (p = 0.17). Cumulative duration of arrhythmias per inducible dog was 87 ± 36 s in CAVB and 30 ± 21 s in HSP (p < 0.05).ConclusionsHigh-septal pacing reduces the magnitude of ventricular electrical remodeling and proarrhythmia in AV block dogs, suggesting a larger role for altered ventricular activation pattern in the generation of ventricular electrical remodeling than previously assumed

Vitamin D Status and Depressive Symptoms in Older Adults:A Role for Physical Functioning?

Objectives: Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms. Methods: Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995–2002) and a younger-old cohort (55–65 years, n = 737, assessed from 2002–2009). Measurements: Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models. Results: Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations >75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed. Conclusions: Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolininduced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-toexcellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner