Cardiac remodeling following myocardial infarction (MI) involves structural and functional alterations in the infarcted and remote viable myocardium that can ultimately lead to heart failure. The underlying mechanisms are not fully understood and, following our previous study of the autofluorescence lifetime and diffuse reflectance signatures of the myocardium in vivo at 16 weeks post MI in rats [Biomed. Opt. Express6(2), 324 (2015)], we here present data obtained at 1, 2 and 4 weeks post myocardial infarction that help follow the temporal progression of these changes. Our results demonstrate that both structural and metabolic changes in the heart can be monitored from the earliest time points following MI using label-free optical readouts, not only in the region of infarction but also in the remote non-infarcted myocardium. Changes in the autofluorescence intensity and lifetime parameters associated with collagen type I autofluorescence were indicative of progressive collagen deposition in tissue that was most pronounced at earlier time points and in the region of infarction. In addition to significant collagen deposition in infarcted and non-infarcted myocardium, we also report changes in the autofluorescence parameters associated with reduced nicotinamide adenine (phosphate) dinucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD), which we associate with metabolic alterations throughout the heart. Parallel measurements of the diffuse reflectance spectra indicated an increased contribution of reduced cytochrome c. Our findings suggest that combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy could provide a useful means to monitor cardiac function in vivo at the time of surgery.

To determine the influence of compression factor upon changes in axial length and choroidal thickness during and following orthokeratology treatment.

We report for the first time the evaluation of oils from the tropical forest tree, Allanblackia, shea butter and palm kernel oil as a potential phase change material for thermal energy storage based upon its thermo-physical and chemical properties. Differential Scanning Calorimetry showed that all the oils were polymorphic and hence exhibited multiple melting/freezing profile over a wide range. For both melting and freezing cycles, Allanblackia oil showed high latent heat of energy (80.53 J/g) with the highest melting point profile (34.74 °C) of all the oils. Thermo-gravimetric analysis showed that all the oil samples were thermally stable and did not degrade within the temperature of interest even though Allanblackia oil showed an increase in weight around 37 °C indicating oxidative instability. Chemical stability was confirmed by FTIR spectra. Of all the oils studied, Allanblackia exhibited a potential for use as a PCM for thermal energy storage if purified to improve oxidative stability.

As populations age and the prevalence of cognitive impairment increases, healthcare professionals and researchers require short, validated cognitive screening instruments (CSIs). As part the EIP-on-AHA Twinning Support Scheme (2016), four reference sites developed the RAPid COmmunity COGnitive screening Programme (RAPCOG) twinning project to validate translated versions of the Quick Mild Cognitive Impairment (Qmci) screen that could be adapted quickly for use with future eHealth screening and assessment programmes. Here we present the cultural adaption and translation of the Qmci-Portuguese (Qmci-P) screen as part of RAPCOG and explore its subsequent validation against two commonly-used CSIs (MMSE-P and MoCA-P) with 93 participants aged ≥65, attending ten day care centres or resident in two long-term care institutions; median age 74 (+/-15), 66% female. The Qmci-P's internal consistency was high (Cronbach's Alpha 0.82), compared with the MoCA (0.79) and SMMSE (0.54). Qmci-P screen scores moderately correlated with the SMMSE (r=0.61, 95% CI:0.45-0.72, p<0.001) and MoCA (r=0.63, 95% CI:0.36-0.80, p<0.001). The Qmci-P screen demonstrates high internal consistency and concurrent validity against more established CSIs and given its brevity (3-5mins), may be preferable for use in community settings. This project shows the potential of the EIP-on-AHA Twinning initiative to promote the scaling-up of innovative good practices.

The exact shape of the dose-response relationship between maternal body mass index (BMI) and the risk of congenital heart defects (CHDs) in infants has not been clearly defined yet. This study aims to further clarify the relationship between maternal obesity and the risk of CHDs in infants by an overall and dose-response meta-analysis.

Recent studies conducted in the mouse and cellular models suggest a stage-specific, differential effect of Akt activity modulation on tumor growth and metastasis in various cancers. In prostate cancer (PCa), although the deletion of Akt1 gene in a neuroendocrine model of TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) blunted oncogenic transformation and tumor growth, Akt1 suppression in the advanced PCa resulted in the activation of transforming growth factor-β pathway and enhanced metastasis to the lungs. Such a dual role for the Akt isoforms and its signaling partners has not been investigated in human PCa. In the current study, we performed genomic database analysis of Akt isoforms and associated pathway molecules in human prostate adenocarcinoma, castration-resistant PCa, neuroendocrine PCa and metastatic PCa for mutations, genetic alterations, mRNA and protein expressions and activating phosphorylations from cBioportal. Results from the protein data analysis from the cBioportal were compared to the results of our data on human PCa tissue analysis and the cellular effects of Akt1 suppression using MK-2206 on PCa cell aggressiveness. Our study indicates the existence of a dual role for Akt1 in PCa and warrants a large-scale analysis of the early and advanced stage PCa clinical samples for further clarity.

Stretchable conductors are essential components in next-generation deformable and wearable electronic devices. The ability of stretchable conductors to achieve sufficient electrical conductivity, however, remains limited under high strain, which is particularly detrimental for charge storage devices. In this study, we present stretchable conductors made from multiple layers of gradient assembled polyurethane (GAP) comprising gold nanoparticles capable of self-assembly under strain. Stratified layering affords control over the composite internal architecture at multiple scales, leading to metallic conductivity in both the lateral and transversal directions under strains of as high as 300%. The unique combination of the electrical and mechanical properties of GAP electrodes enables the development of a stretchable lithium-ion battery with a charge-discharge rate capability of 100 mAh g-1 at a current density of 0.5 A g-1 and remarkable cycle retention of 96% after 1000 cycles. The hierarchical GAP nanocomposites afford rapid fabrication of advanced charge storage devices.

The handful of studies (<30) on cancer and residential segregation have focused on racial segregation, primarily at the city/town level. We tested a priori hypotheses about choice of measure and level by extending use of the Index of Concentration at the Extremes (ICE) to quantify both economic and racial residential segregation, singly and combined, and conducted analyses for the total population and stratified by race/ethnicity.

Lifestyle factors are associated with overall breast cancer risk, but less is known about their associations, alone or jointly, with risk of specific breast cancer subtypes.

Despite randomized data demonstrating better overall survival favoring radical nephrectomy, partial nephrectomy continues to be the treatment of choice for low-stage renal cell carcinoma.

Genetic testing of cancer samples primarily focuses on protein-coding regions, despite most mutations arising in noncoding DNA. Noncoding mutations can be pathogenic if they disrupt gene regulation, but the benefits of assessing promoter mutations in driver genes by panel testing has not yet been established. This is especially the case in colorectal cancer, for which few putative driver variants at regulatory elements have been reported.

Diet is an important risk factor for cancer that is amenable to intervention. Estimating the cancer burden associated with diet informs evidence-based priorities for nutrition policies to reduce cancer burden in the United States.

Fucosylated chondroitin sulfates (FCSs) from sea cucumbers have repetitive structures that exhibit minor structural differences based on the organism from which they are recovered. A detailed characterization of FCSs and their derivatives is important to establish their structure-activity relationship in the development of new anticoagulant drugs. In the current study, online hydrophilic interaction chromatography-Fourier transform mass spectrometry (FTMS) was applied to analyze the FCS oligosaccharides generated by selective degradation from four species of sea cucumbers, Isostichopus badionotus, Pearsonothuria graeffei, Holothuria mexicana and Acaudina molpadioides. These depolymerized FCS fragments were quantified and compared using the glycomics software package, GlycReSoft. The quantified fragments mainly had trisaccharide-repeating compositions and showed significant differences in fucosylation (including its sulfation) among different species of sea cucumbers. Detailed analysis of FTMS ion peaks and top-down nuclear magnetic resonance spectroscopy of native FCS polysaccharides verified the accuracy of this method. Thus, a new structural model for FCS chains from these different sea cucumbers was defined. This bottom-up approach provides rich detailed structural analysis and provides quantitative information with high accuracy and reproducibility and should be suitable for the quality control in FCSs as well as their oligosaccharides.

The growing emergence of azole-resistant Aspergillus fumigatus strains worldwide is a major concern for current systemic antifungal treatment. Here we report antifungal activities of a novel inhaled triazole, PC1244, against a collection of multi-azole-resistant A. fumigatus strains.

Glycogen synthase kinase-3β (GSK3β) is a critical regulator of the balance between long-term depression and long-term potentiation which is essential for learning and memory. Our previous study demonstrated that GSK3β activity is highly induced during cocaine memory reactivation, and that reconsolidation of cocaine reward memory is attenuated by inhibition of GSK3β. NMDA receptors and protein phosphatase 1 (PP1) are activators of GSK3β. Thus, this study investigated the roles of NMDA receptor subtypes and PP1in the reconsolidation of cocaine contextual reward memory. Cocaine contextual memories were established and evaluated using cocaine conditioned place preference methods. The regulation of GSK3β activity in specific brain areas was assessed by measuring its phosphorylation state using immunoblot assays. Mice underwent cocaine place conditioning for 8 days and were tested for place preference on day 9. Twenty-four hours later, mice were briefly confined to the compartment previous paired with cocaine to reactivate cocaine-associated memories. Administration of the GluN2A- and GluN2B-NMDA receptor antagonists, NVP-AAM077 and ifenprodil, respectively, immediately following recall abrogated an established cocaine place preference, while preventing the activation of GSK3β in the amygdala, nucleus accumbens, and hippocampus during cocaine memory reactivation. PP1 inhibition with okadaic acid also blocked the activation of GSK3β and attenuated a previously established cocaine place preference. These findings suggest that the dephosphorylation of GSK3β that occurred upon activation of cocaine-associated reward memories may be initiated by the activation of PP1 during the induction of NMDA receptor-dependent reconsolidation of cocaine mnemonic traces. Moreover, the importance of NMDA receptors and PP1 in reconsolidation of cocaine memory makes them potential therapeutic targets in treatment of cocaine use disorder and prevention of relapse.

The K+ voltage-gated channel subfamily H member 2 (KCNH2) transports the rapid component of the cardiac delayed rectifying K+ current. The aim of this study was to characterize the biophysical properties of a C-terminus-truncated KCNH2 channel, G1006fs/49 causing long QT syndrome type II in heterozygous members of an Italian family. Mutant carriers underwent clinical workup, including 12-lead electrocardiogram, transthoracic echocardiography and 24-hour ECG recording. Electrophysiological experiments compared the biophysical properties of G1006fs/49 with those of KCNH2 both expressed either as homotetramers or as heterotetramers in HEK293 cells. Major findings of this work are as follows: (a) G1006fs/49 is functional at the plasma membrane even when co-expressed with KCNH2, (b) G1006fs/49 exerts a dominant-negative effect on KCNH2 conferring specific biophysical properties to the heterotetrameric channel such as a significant delay in the voltage-sensitive transition to the open state, faster kinetics of both inactivation and recovery from the inactivation and (c) the activation kinetics of the G1006fs/49 heterotetrameric channels is partially restored by a specific KCNH2 activator. The functional characterization of G1006fs/49 homo/heterotetramers provided crucial findings about the pathogenesis of LQTS type II in the mutant carriers, thus providing a new and potential pharmacological strategy.

Fungal plant pathogens secrete effector proteins and metabolites to cause disease. Additionally, some species transfer small RNAs (sRNAs) into plant cells to silence host mRNAs through complementary base pairing and suppress plant immunity. The fungus Sclerotinia sclerotiorum infects over 600 plant species, but little is known about the molecular processes that govern interactions with its many hosts. In particular, evidence for the production of sRNAs by S. sclerotiorum during infection is lacking. We sequenced sRNAs produced by S. sclerotiorum in vitro and during infection of two host species, Arabidopsis thaliana and Phaseolus vulgaris. We found that S. sclerotiorum produces at least 374 distinct highly abundant sRNAs during infection, mostly originating from repeat-rich plastic genomic regions. We predicted the targets of these sRNAs in A. thaliana and found that these genes were significantly more down-regulated during infection than the rest of the genome. Predicted targets of S. sclerotiorum sRNAs in A. thaliana were enriched for functional domains associated with plant immunity and were more strongly associated with quantitative disease resistance in a genome-wide association study (GWAS) than the rest of the genome. Mutants in A. thaliana predicted sRNA target genes SERK2 and SNAK2 were more susceptible to S. sclerotiorum than wild-type, suggesting that S. sclerotiorum sRNAs may contribute to the silencing of immune components in plants. The prediction of fungal sRNA targets in plant genomes can be combined with other global approaches, such as GWAS, to assist in the identification of plant genes involved in quantitative disease resistance.

The calcium-binding protein calbindin-D28K, or calb1, is expressed at higher levels by dopamine (DA) neurons originating in the ventral tegmental area (VTA) than in the adjacent substantia nigra pars compacta (SNc). Calb1 has received attention for a potential role in neuroprotection in Parkinson's disease. The underlying physiological roles for calb1 are incompletely understood. We used cre-loxP technology to knock down calb1 in mouse DA neurons to test whether calb1 governs axonal release of DA in the striatum, detected using fast-scan cyclic voltammetry ex vivo. In the ventral but not dorsal striatum, calb1 knockdown elevated DA release and modified the spatiotemporal coupling of Ca2+ entry to DA release. Furthermore, calb1 knockdown enhanced DA uptake but attenuated the impact of DA transporter (DAT) inhibition by cocaine on underlying DA release. These data reveal that calb1 acts through a range of mechanisms underpinning both DA release and uptake to limit DA transmission in the ventral but not dorsal striatum.

While sequencing ancient DNA (aDNA) from archaeological material is now commonplace, very few attempts to sequence ancient transcriptomes have been made, even from typically stable deposition environments such as permafrost. This is presumably due to assumptions that RNA completely degrades relatively quickly, particularly when dealing with autolytic, nuclease-rich mammalian tissues. However, given the recent successes in sequencing ancient RNA (aRNA) from various sources including plants and animals, we suspect that these assumptions may be incorrect or exaggerated. To challenge the underlying dogma, we generated shotgun RNA data from sources that might normally be dismissed for such study. Here, we present aRNA data generated from two historical wolf skins, and permafrost-preserved liver tissue of a 14,300-year-old Pleistocene canid. Not only is the latter the oldest RNA ever to be sequenced, but it also shows evidence of biologically relevant tissue specificity and close similarity to equivalent data derived from modern-day control tissue. Other hallmarks of RNA sequencing (RNA-seq) data such as exon-exon junction presence and high endogenous ribosomal RNA (rRNA) content confirms our data's authenticity. By performing independent technical library replicates using two high-throughput sequencing platforms, we show not only that aRNA can survive for extended periods in mammalian tissues but also that it has potential for tissue identification. aRNA also has possible further potential, such as identifying in vivo genome activity and adaptation, when sequenced using this technology.

Some experts have proposed combating rising drug prices by promoting brand-brand competition, a situation that is supposed to arise when multiple US Food and Drug Administration (FDA)-approved brand-name products in the same class are indicated for the same condition. However, numerous reports exist of price increases following the introduction of brand-name competition, suggesting that it may not be effective. We performed a systematic literature review of the peer-reviewed health policy and economics literature to better understand the interplay between new drug entry and intraclass drug prices.