BACKGROUND:Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription ...factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.
METHODS:We screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.
RESULTS:We found that a combination of the transforming growth factor-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; we observed beating cells as early as 1 week after reprogramming compared with 6 to 8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared with those exposed to only GMT. Human cardiac reprogramming was similarly enhanced on transforming growth factor-β and WNT inhibition and was achieved most efficiently with GMT plus myocardin.
CONCLUSIONS:Transforming growth factor-β and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.
Solid‐state polymer electrolytes (SPEs) with high ionic conductivity are desirable for next generation lithium‐ and sodium‐ion batteries with enhanced safety and energy density. Nanoscale fillers ...such as alumina, silica, and titania nanoparticles are known to improve the ionic conduction of SPEs and the conductivity enhancement is more favorable for nanofillers with a smaller size. However, aggregation of nanoscale fillers in SPEs limits particle size reduction and, in turn, hinders ionic conductivity improvement. Here, a novel poly(ethylene oxide) (PEO)‐based nanocomposite polymer electrolyte (NPE) is exploited with carbon quantum dots (CQDs) that are enriched with oxygen‐containing functional groups. Well‐dispersed, 2.0–3.0 nm diameter CQDs offer numerous Lewis acid sites that effectively increase the dissociation degree of lithium and sodium salts, adsorption of anions, and the amorphicity of the PEO matrix. Thus, the PEO/CQDs‐Li electrolyte exhibits an exceptionally high ionic conductivity of 1.39 × 10−4 S cm−1 and a high lithium transference number of 0.48. In addition, the PEO/CQDs‐Na electrolyte has ionic conductivity and sodium ion transference number values of 7.17 × 10−5 S cm−1 and 0.42, respectively. It is further showed that all solid‐state lithium/sodium rechargeable batteries assembled with PEO/CQDs NPEs display excellent rate performance and cycling stability.
Well‐dispersed carbon quantum dots with oxygen‐containing functional groups are introduced to form highly ion‐conducting solid‐state composite electrolytes. The composite electrolytes with excellent electrochemical characteristics, including high ionic conductivities and high lithium/sodium ion transference numbers, enable the fabrication of all solid‐state Li and Na batteries with significantly enhanced cycling stability and rate performance.
Abstract
Among 626 participants of the Men’s Lifestyle Validation Study (2011–2013), we evaluated the validity and reproducibility of a self-administered 152-item semiquantitative food frequency ...questionnaire (SFFQ) using two 7-day dietary records (7DDRs), 4 Automated Self-Administered 24-hour dietary recalls (ASA24s), four 24-hour urine samples, 1 doubly labeled water measurement (repeated in 104 participants), and 2 fasting blood samples, collected over 15 months. Compared with 7DDRs, SFFQs underestimated energy intake, macronutrients, and sodium intake but overestimated some micronutrients. The mean of the Spearman correlation coefficients was 0.66 (range, 0.38–0.88) between 46 energy-adjusted nutrients estimated from 7DDRs and the final SFFQ, deattenuated for within-person variation in the 7DDRs. These deattenuated correlations were similar using ASA24s as the comparison. Relative to biomarkers, SFFQs underestimated energy, sodium, and protein intakes, as well as the sodium:potassium ratio. The energy-adjusted correlations between the final SFFQ and the biomarkers were slightly lower than the correlations between the SFFQ and 7DDRs. Using the method of triads to calculate validity coefficients, the median validity coefficient between SFFQ and true intake was 0.65 and 0.69 using 7DDRs and ASA24s, respectively, as the third method. These data indicate that this SFFQ provided reasonably valid estimates for a wide range of nutrients when evaluated by multiple comparison methods.
This study was designed to examine the cellular effects of feeding oxidized fats to broilers in the presence or absence of the antioxidant Santoquin
®. Although bird performance may be affected by ...the addition of rancid feed ingredients in the diet, little is known about the mechanism responsible for performance effects. In this study, gain, feed conversion and hematocrit were negatively affected by the feeding of oxidized fat (4 meq kg
−1 diet). All these effects were ameliorated by the inclusion of ethoxyquin in the diet at 125 ppm. Results indicated that the gastrointestinal epithelium responded to oxidant stress with an increase in cell turnover. Hepatic cell proliferation increased. The gut associated immune system was also affected. Although plasma cell numbers were not affected based on histology, the concentration of immunoglobulin in the intestinal tissue appeared to be lower. These indicators of oxidative stress may be related to the poor performance seen in animals fed unstabilized diets containing oxidized ingredients.
We compared the effectiveness of 2-hydroxy-4-(methylthio) butanoic acid (HMB) and DL-methionine (DLM) as sources of L-methionine activity in methionine-deficient primary cultures of pig liver cells ...and methionine-deficient early-weaned pigs. Viable hepatocytes were obtained from minced pig liver and maintained in a high density, differentiated, nonproliferation cell culture system. Culture medium was supplemented with HMB, DLM, or L-methionine, and cells were pulse-dosed with L14C(U)leucine for 24 h to determine the level of protein synthesis. Leucine incorporation per milligram of protein indicated a six-to eightfold increase in protein synthesis (P .01) with methionine levels between 5 and 10 micromolar, regardless of source of methionine activity. Two 24-pen replicate methionine dose titrations were conducted with 95 early-weaned commercial crossbred pigs. The pelleted corn, dried whey, and porcine plasma basal diet contained 1.5% lysine, .23% methionine, and .48% cystine and was supplemented with 0, .05, or .10% methionine activity as DLM or HMB for 21 d. There was a 134, 104, and 61% increase (P .01) in cumulative ADG for each successive week on study with a 30 and 19% improvement in feed/gain (P .01) after 7 and 14 d. Performance responses due to source of methionine activity did not differ and slope ratio potency determinations (gain vs intake of methionine source) of HMB vs DLM indicated a 119, 111, and 95% relative activity for cumulative weekly performance. These results support the hypothesis that HMB and DLM provide equimolar levels of methionine activity in swine
To determine the prevalence of sarcopenia in stroke survivors using different methodologies, and compare a subset of the stroke group to age-, sex-, and body mass index (BMI)-matched nonstroke ...control counterparts.
Cohort study.
A Veterans Affairs medical center and a university hospital.
Mild to moderately disabled participants >6 months after onset of stroke aged 40 to 84 years (N=190, 61% men, 57% African American; mean BMI ± SEM, 29±1kg/m
).
Not applicable.
Dual-energy x-ray absorptiometry scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using 4 established methods: (1) ALM/height
(ALM/ht
); (2) European Working Group on Sarcopenia in Older Persons; (3) International Working Group on Sarcopenia; and (4) ALM/BMI.
Sarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age ±4 years and BMI ±2.5kg/m
had higher prevalence rates compared with their nonstroke counterparts (13.2% vs 5.3%, P<.0001). ALM/ht
was related to 6-minute walking speed (r=.28, P<.01) and peak oxygen consumption (L/min: r=.58, P<.0001) for the stroke group.
Stroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race compared with nonstroke individuals.
While education and advocacy regarding behavioral health (BH) integration in primary care have been in full force at the state and national level for many years, specialty care BH integration has not ...received the same attention in terms of practice transformation, workforce development, and payment reform. Models of BH care have been tested in primary care and can be easily adapted to improve specialty patient care. There are many opportunities for using the knowledge base gained from integrated primary care to help move integration forward in the specialty medical setting. The timing for this is rife, as the benefits of integrated BH for patient health outcomes are well established.
A child's obesity is generally perceived by the public to be under the control of the child's parents. While the health consequences of childhood obesity are well understood, less is known about ...psychological and social effects of having an obese child on parents. We set out to characterize stigma and courtesy stigma experiences surrounding obesity among children with Bardet-Biedl syndrome (BBS), a multisystem genetic disorder, and their parents.
Twenty-eight parents of children with BBS participated in semi-structured interviews informed by social stigmatization theory, which describes courtesy stigma as parental perception of stigmatization by association with a stigmatized child. Parents were asked to describe such experiences.
Parents of children with BBS reported the child's obesity as the most frequent target of stigmatization. They perceived health care providers as the predominant source of courtesy stigma, describing interactions that resulted in feeling devalued and judged as incompetent parents.
Parents of children with BBS feel blamed by others for their child's obesity and described experiences that suggest health care providers may contribute to courtesy stigma and thus impede effective communication about managing obesity. Health care providers may reinforce parental feelings of guilt and responsibility by repeating information parents may have previously heard and ignoring extremely challenging barriers to weight management, such as a genetic predisposition to obesity. Strategies to understand and incorporate parents' perceptions and causal attributions of their children's weight may improve communication about weight control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND AND PURPOSE—A short-term increase in dietary nitrate (NO3) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates ...into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226).
METHODS—Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System.
RESULTS—Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=−0.015, P=0.002) and lower mean CCA-IMT (B=−0.012, P=0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors (P≤0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models (P=0.02).
CONCLUSIONS—Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event.
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