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The use of bioactive scaffolds in conjunction with stem cell therapies for cardiac repair after a myocardial infarction shows significant promise for clinical translation. We performed a systematic review and meta-analysis of preclinical trials that investigated the use of bioactive scaffolds to support stem cell-aided cardiac regeneration, in comparison to stem cell treatment alone. Cochrane Library, Medline, Embase, PubMed, Scopus, Web of Science, and grey literature were searched through April 23, 2020 and 60 articles were included in the final analysis. The overall effect size observed in scaffold and stem cell-treated small animals compared to stem cell-treated controls for ejection fraction (EF) was 7.98 [95% confidence interval (CI) 6.36, 9.59] and for fractional shortening (FS) was 5.50 [95% CI 4.35, 6.65] in small animal models. The largest improvements in EF and FS were observed when hydrogels were used (MD = 8.45 [95% CI 6.46, 10.45] and MD = 5.76 [95% CI 4.46, 7.05], respectively). Subgroup analysis revealed that cardiac progenitor cells had the largest effect size for FS, and was significant from pluripotent, mesenchymal and endothelial stem cell types. In large animal studies, the overall improvement of EF favoured the use of stem cell-embedded scaffolds compared to direct injection of cells (MD = 10.49 [95% CI 6.30, 14.67]). Significant publication bias was present in the small animal trials for EF and FS. selleck chemicals llc This study supports the use of bioactive scaffolds to aid in stem cell-based cardiac regeneration. Hydrogels should be further investigated in larger animal models for clinical translation.Biological treatments are one of the medical breakthroughs in the twenty-first century. The initial enthusiasm pushed the field towards indiscriminatory use of cell therapy regardless of the pathophysiological particularities of underlying conditions. In the reparative and regenerative cardiovascular field, the results of the over two decades of research in cell-based therapies, although promising still could not be translated into clinical scenario. Now, when we identified possible deficiencies and try to rebuild its foundations rigorously on scientific evidence, development of potency assays for the potential therapeutic product is one of the steps which will bring our goal of clinical translation closer. Although, highly challenging, the potency tests for cell products are considered as a priority by the regulatory agencies. In this paper we describe the main characteristics and challenges for a cell therapy potency test focusing on the cardiovascular field. Moreover, we discuss different steps and types of assays that should be taken into consideration for an eventual potency test development by tying together two fundamental concepts target disease and expected mechanism of action. Development of potency assays for cell-based products consists in understanding the pathophysiology of the disease, identifying potential mechanisms of action (MoA) to counteract it and finding the most suitable cell-based product that exhibits these MoA. When applied, the potency assay needs to correlate bioactivity of the product, via a measurement related to the MoA, with treatment efficacy. However, in the cardiovascular field, the process faces several challenges and high requirements.The overarching mission of the Einstein-Nathan Shock Center (E-NSC) is to make scientific discoveries in geroscience, leveraging on the expertise in our center in 6 out of the 7 pillars of aging, and to translate their effects towards drug discovery. The relevance of this basic biology of aging discoveries to humans will be confirmed through the unique gero-human resource at E-NSC. This is achieved through services provided by E-NSC, connectivity among its members, attracting worldwide investigators, and providing them with the opportunities to become future leaders. The two central components of the E-NSC are (a) cutting-edge research programs and (b) unique E-NSC research support cores. E-NSC scientists lead NIH-supported cutting-edge research programs that integrate key hallmarks of aging including proteostasis/autophagy, metabolism/inflammaging, genetic/epigenetics, stem cells/regeneration, and translational aging/longevity. Since the inception of the E-NSC, the well-integrated, collaborative, and innovative nature of the multiple supporting state-of-the-art E-NSC research cores form the bedrock of research success at the E-NSC. The three state-of-the-art E-NSC research cores, (i) Proteostasis of Aging Core (PAC), (ii) the Health Span Core (HSC), and (iii) the Human Multi-Omics Core (HMOC), have allowed impressive expansion of translational biological research programs. Expansion was facilitated through the wealth of data coming from genomics/proteomics and metabolomic analysis on human longevity studies, due to access to a variety of biological samples from elderly subjects in clinical trials with aging-targeting drugs, and new drug design services via the PAC to target the hallmarks of aging.Human DNA methylation profiles have been used successfully to develop highly accurate biomarkers of aging ("epigenetic clocks"). Although these human epigenetic clocks are not immediately applicable to all species of the animal kingdom, the principles underpinning them appear to be conserved even in animals that are evolutionarily far removed from humans. This is exemplified by recent development of epigenetic clocks for mice and other mammalian species. Here, we describe epigenetic clocks for the domestic cat (Felis catus), based on methylation profiles of CpGs with flanking DNA sequences that are highly conserved between multiple mammalian species. Methylation levels of these CpGs are measured using a custom-designed Infinium array (HorvathMammalMethylChip40). From these, we present 3 epigenetic clocks for cats; of which, one applies only to blood samples from cats, while the remaining two dual-species human-cat clocks apply both to cats and humans. We demonstrate that these domestic cat clocks also lead to high age correlations in cheetahs, tigers, and lions. It is expected that these epigenetic clocks for cats possess the potential to be further developed for monitoring feline health as well as being used for identifying and validating anti-aging interventions.Between 50-80% of children with autism spectrum disorder (ASD) have insomnia, which adversely affects their mental and physical health. However, there is no consensus to-date on suitable tools for insomnia screening and monitoring in daily clinical practice. An expert panel of child neuropsychiatry and sleep specialists, with expertise in children with neurodevelopmental disabilities, recommends (1) performing insomnia screening of all children with ASD; (2) considering discussion or referral to a sleep specialist when comorbid sleep disorders are suspected. The panel further developed structured, brief screening and monitoring tools to facilitate insomnia screening and management in daily practice, monitor treatment effectiveness and standardize and compare outcomes across clinical settings to improve care and well-being of children with ASD and their families.Estrogens have pleiotropic effects on many reproductive and non-reproductive tissues and organs including the mammary gland, uterus, ovaries, vagina, and endothelium. Estrogen receptor α functions as the principal mediator of estrogenic action in most of these tissues. Estetrol (E4) is a native fetal estrogen with selective tissue actions that is currently approved for use as the estrogen component in a combined oral contraceptive and is being developed as a menopause hormone therapy (MHT, also known as hormone replacement therapy). However, exogenous hormonal treatments, in particular MHTs, have been shown to promote the growth of preexisting breast cancers and are associated with a variable risk of breast cancer depending on the treatment modality. Therefore, evaluating the safety of E4-based formulations on the breast forms a crucial part of the clinical development process. This review highlights preclinical and clinical studies that have assessed the effects of E4 and E4-progestogen combinations on the mammary gland and breast cancer, focusing in particular on the estrogenic and anti-estrogenic properties of E4. We discuss the potential advantages of E4 over current available estrogen-formulations as a contraceptive and for the treatment of symptoms due to menopause. We also consider the potential of E4 for the treatment of endocrine-resistant breast cancer.Iodine excess typically affects thyroid function in the human body and may damage carotid artery. Four investigation plots with different water iodine levels were selected in Shandong Province, China. These included a low, medium, and high iodine group and an iodine excess group whose water iodine content was  300 μg/L, respectively. Residents aged 20-65 years answered a questionnaire and underwent carotid artery ultrasonography, and their height, weight, and urinary iodine concentrations were measured. A total of 2026 individuals participated in the study. Urinary iodine concentration increased with increased water iodine levels. The medial thickening rate and intimal roughness rate in the iodine excess group were significantly higher than in the other three groups. After controlling for factors such as gender, age, and BMI, iodine excess remained as a risk factor for carotid intima-media thickening. Excess water iodine in the external environment is a risk factor for intima-media thickening of the carotid artery, suggesting that iodine excess may cause vascular injury and promote atherosclerosis.The purpose of this study was to evaluate behavioral strategies to minimize procedural distress associated with in-office tympanostomy tube placement for children without general anesthesia, sedation, or papoose-board restraints. 120 6-month- to 4-year-olds and 102 5- to 12-year-olds were treated at 16 otolaryngology practices. Mean age of children was 4.7 years old (SD = 3.18 years), with more boys (58.1%) than girls (41.9%). The cohort included 14% Hispanic or Latinx, 84.2% White, 12.6% Black, 1.8% Asian and 4.1% 'Other' race and ethnicity classifications. The in-office tube placement procedure included local anesthesia via lidocaine/epinephrine iontophoresis and tube placement using an integrated and automated myringotomy and tube delivery system. Behavioral strategies were used to minimize procedural distress. Anxiolytics, sedation, or papoose board were not used. Pain was measured via the faces pain scale-revised (FPS-R) self-reported by the children ages 5 through 12 years. Independent coders supervised by a psychologist completed the face, legs, activity, cry, consolability (FLACC) behavior observational rating scale to quantify children's distress. Mean FPS-R score for tube placement was 3.30, in the "mild' pain range, and decreased to 1.69 at 5-min post-procedure. Mean tube placement FLACC score was 4.0 (out of a maximum score of 10) for children ages 6 months to 4 years and was 0.4 for children age 5-12 years. Mean FLACC score 3-min post-tube placement was 1.3 for children ages 6 months to 4 years and was 0.2 for children age 5-12 years. FLACC scores were inversely correlated with age, with older children displaying lower distress. The iontophoresis, tube delivery system and behavioral program were associated with generally low behavioral distress. These data suggest that pediatric tympanostomy and tube placement can be achieved in the outpatient setting without anxiolytics, sedatives, or mechanical restraints.