Cardiac PPARα Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition

Gene expression data obtained in mouse heart indicate that increased expression for the nuclear receptor, peroxisomal proliferator activated receptor α (PPARα), prompts the postnatal transition from predominantly carbohydrate to fatty acid oxidation preference. However, no phenotypic or proteomic data are available to confirm downstream signaling and metabolic transition in mice. We studied the hypothesis that shifts in nuclear receptor expression trigger the newborn metabolic switch in a newborn sheep. This species is well characterized with regards to developmental changes in substrate oxidative metabolism. Heart tissues from fetal (130 days gestation), newborn ≤24 hours, and 30-day old lambs were evaluated for protein expression from multiple enzymes controlling oxidative metabolism as well as principal nuclear receptors and coactivators. Although muscle and liver type carnitine palmitoyl transferases I showed no significant changes to correspond to the metabolic transition, hexokinase II protein content showed a profound transient drop, and pyruvate dehydrogenase kinase steadily increased. PPARα showed no increases preceding or during the transition, while peroxisomal proliferator activated receptor gamma coactivator-1 (PGC-1) increased approximately 20-fold transiently in newborn heart in conjunction with significant increases in thyroid hormone receptor α1 and retinoid-activated receptor α. These data challenge the paradigm that increases in PPARα prompt the postnatal metabolic switch, and suggest that other nuclear receptors play a major role. As thyroid hormone (TH) modulates PGC-1 expression in sheep during development, these data further suggest that well-characterized perinatal TH surge in sheep contributes to this metabolic switch

Megachile (Megachile) montivaga (Hymenoptera: Megachilidae) nesting in live thistle (Asteraceae: Cirsium)

Although Megachile Latreille (leafcutter bees) are well known for their diverse nesting habits, records of the genus nesting in live plants are rare.  Here, we report the widespread Megachile (Megachile) montivaga Cresson nesting in live thistle (Cirsium neomexicanum Gray), the first explicit record of this behavior in the Nearctic

Long-lasting Effects of Perinatal Exposure to Brominated Flame Retardant on Male Reproductive Outcomes in Rat Model

Meta-analysis of 101 studies published between 1934 and 1996 indicates that mean sperm concentration decreased around 50% during this period. More recent studies have found alarmingly poor semen quality in the general population of Northern Europe. Additional adverse trends include increased incidence of testicular cancer, and congenital malformations such as cryptorchidism and hypospadias. Testicular germ cell cancers increased by about 400% over the period of 50 years in industrialized countries. Decreased quality of male reproductive health has been linked to environmental endocrine disruptors exposure. However, the ability of xenobiotics to produce long-lasting effects and mechanisms of perturbation of the male reproductive system following developmental exposures are not well understood. Both animal experiments and human studies show male reproductive toxicity to polybrominated diphenyl ethers (PBDE), a group of ubiquitous, persistent, and bioaccumulative environmental xenobiotics. Here we report the result of experiment in which pregnant Wistar rats were fed 0.2 mg/kg body weight BDE-47 (the most ubiquitous PBDE congener) daily starting from the eighth day of pregnancy until weaning. Multiple endpoints of male reproductive health were assessed in offspring on postnatal week 20: testis size, sperm production, morphology, motility, circulating testosterone, select gene expression in prostate (qRT-PCR) and all-genome gene expression in testis (RNA-seq). Seventeen weeks after exposure was abolished testis size was significantly smaller in adult rats and genes of inflammatory response were significantly upregulated in testis tissue among other results. Our findings confirm male-reproductive toxicity of PBDE and identify inflammatory response as a long lasting mechanism of repro-toxicity triggered by perinatal exposure

Major coronary artery anomalies in a pediatric population: incidence and clinical importance

AbstractOBJECTIVESWe sought to prospectively determine the incidence and clinical significance of major coronary artery anomalies in asymptomatic children using transthoracic two-dimensional echocardiography.BACKGROUNDAnomalous origins of the left main coronary artery (ALMCA) from the right sinus of Valsalva or anomalous origins the right coronary artery (ARCA) from the left sinus are rarely diagnosed in children and can cause sudden death, especially in young athletes. Because most patients are asymptomatic, the diagnosis is often made post mortem. No study to date has prospectively identified anomalous coronary arteries in asymptomatic children in the general population.METHODSAfter serendipitously identifying an index case with ALMCA, we examined proximal coronary artery anatomy in children with otherwise anatomically normal hearts who were referred for echocardiography. In those diagnosed with ALMCA or ARCA, we performed further tests.RESULTSWithin a three-year period, echocardiograms were obtained in 2,388 children and adolescents. Four children (0.17%) were identified with anomalous origin of their coronary arteries, and angiograms, exercise perfusion studies and/or stress tests were then performed. One ARCA patient had decreased perfusion in the right coronary artery (RCA) perfusion area and showed ventricular ectopy on electrocardiogram (ECG) at rest that diminished but did not resolve with exercise. A second patient with ALMCA had atrial tachycardia immediately after exercise, with inferior and lateral ischemic changes on ECG and frequent junctional and/or ventricular premature complexes both at rest and recovery.CONCLUSIONSThis study demonstrates that although anomalous origins of coronary arteries are rare in asymptomatic children, the prevalence is greater than that found in other prospective studies. Ischemia can occur with both ALMCA and ARCA even though patients remain asymptomatic. Because of the high risk of sudden cardiac death, aggressive surgical management and close follow-up are necessary

Development and Utility of Quality Metrics for Ambulatory Pediatric Cardiology in Kawasaki Disease.

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an "open comments" process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network

Does malnutrition influence outcome in children undergoing congenital heart surgery in a developing country?

Background Most children undergoing cardiac surgery for congenital heart disease (CHD) in developing countries are malnourished. Malnutrition is known as a co-morbidity factor that might predict and influence outcomes after surgery. Objectives To evaluate the effect of malnutrition and other associated risk factors on post-operative outcomes in children with CHDs underwent cardiac surgery. Methods We conducted a retrospective cohort study in a single center tertiary pediatric cardiac intensive care unit (PCICU) in Indonesia. Our cohort included all children between 5 and 36 months of age undergoing congenital heart surgery with cardiopulmonary bypass from November 2011 until February 2014. Outcomes measured were the length of intubation and the length of ICU stay. Variables for potential influence investigated were the nutritional status, age, gender, type of cardiac anomaly (acyanotic vs. cyanotic), Aristotle score, cardiopulmonary bypass time, aortic cross-clamp time, and Pediatric Risk of Mortality (PRISM) III score. Results Out of 249 patients included, 147 (59%) showed malnourishment on admission. Malnourished patients were significantly younger in age, presented with an acyanotic heart defects, and had higher PRISM III score. Additionally, they also had a longer mechanical ventilation time and ICU stay than those with a normal nutritional status. After adjusting for various variables using a multiple logistic regression model it could be demonstrated that a higher Z-score for weight to age was a significant protective factor for the intubation time of more than 29 hours with an odds ratio of 0.66 (95% CI 0.48 to 0.92, P = 0.012). Non-malnourished patients had a 49% significantly higher chance for extubation with a hazard ratio of 1.49 (95% CI 1.12 to 1.99, P= 0.007). Conclusion Malnourishment is clearly associated in a linear fashion with longer mechanical ventilation and ICU stay. As one of significant and potentially treatable co-morbidity factors, prevention of malnourishment by early diagnosis and optimal timing for surgery is important

Privacy-Aware Recommender Systems Challenge on Twitter's Home Timeline

Recommender systems constitute the core engine of most social network platforms nowadays, aiming to maximize user satisfaction along with other key business objectives. Twitter is no exception. Despite the fact that Twitter data has been extensively used to understand socioeconomic and political phenomena and user behaviour, the implicit feedback provided by users on Tweets through their engagements on the Home Timeline has only been explored to a limited extent. At the same time, there is a lack of large-scale public social network datasets that would enable the scientific community to both benchmark and build more powerful and comprehensive models that tailor content to user interests. By releasing an original dataset of 160 million Tweets along with engagement information, Twitter aims to address exactly that. During this release, special attention is drawn on maintaining compliance with existing privacy laws. Apart from user privacy, this paper touches on the key challenges faced by researchers and professionals striving to predict user engagements. It further describes the key aspects of the RecSys 2020 Challenge that was organized by ACM RecSys in partnership with Twitter using this dataset.Comment: 16 pages, 2 table

MuRF1 mono-ubiquitinates TRα to inhibit T3-induced cardiac hypertrophy in vivo

Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth and participates in homeostasis of the heart. T3 activates pro-survival pathways including Akt and mTOR. Treatment with T3 after myocardial infarction is cardioprotective and promotes elements of physiological hypertrophic response after cardiac injury. Although T3 is known to benefit the heart, very little about its regulation at the molecular level has been described to date. The ubiquitin proteasome system (UPS) regulates nuclear hormone receptors such as estrogen, progesterone, androgen, and glucocorticoid receptors by both degradatory and non-degradatory mechanisms. However, how the UPS regulates T3-mediated activity is not well understood. In this study, we aim to determine the role of the muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) in regulating T3-induced cardiomyocyte growth. An increase in MuRF1 expression inhibits T3-induced physiological cardiac hypertrophy, whereas a decrease in MuRF1 expression enhances T3’s activity both in vitro and in cardiomyocytes in vivo. MuRF1 interacts directly with TRα to inhibit its activity by posttranslational ubiquitination in a non-canonical manner. We then demonstrated that a nuclear localization apparatus that regulates/inhibits nuclear receptors by sequestering them within a subcompartment of the nucleus was necessary for MuRF1 to inhibit T3 activity. This work implicates a novel mechanism that enhances the beneficial T3 activity specifically within the heart, thereby offering a potential target to enhance cardiac T3 activity in an organ-specific manner

Kawasaki Disease Shock Syndrome vs Classical Kawasaki Disease: A Meta-analysis and Comparison With SARS-CoV-2 Multisystem Inflammatory Syndrome.

BACKGROUND: The emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD) and more specifically Kawasaki disease shock syndrome (KDSS), prompted us to explore KDSS in a preamble of a systematic comparison between the two conditions. METHODS: We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls. RESULTS: A total of ten case-control series were included in the meta-analysis. KDSS patients were older (38.4 ± 30.6 vs. 21.9±19.5 months; P<0.001) compared to standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher CRP (59.4±29.2 mg/dL vs. 20.8±14.8 mg/dL; p<0.001), lower albumin (2.7±0.5 g/dL vs. 3.3±0.5 g/dL; p<0.01), and lower platelets (255±149 109/L vs. 394±132 109/L; p<0.001) but only borderline higher WBC's (p=0.06). Differences in ALT, AST and ESR were non-significant. The odds of IVIG resistance (44.4% vs. 9.6%; (p<0.001) and the hospital length of stay (10.9±5.8 vs. 5.0±3.0 days; p<0.001) were higher in KDSS as were the odds of coronary artery abnormalities (33.9% vs. 8.6%; p<0.001). CONCLUSION: This first meta-analysis on KDSS versus KD represents a basis for future works on KDSS and opens the opportunity for future multicenter studies in the search of causal relationships between presenting elements and the eventual complications of KDSS. The similarities between SARS-CoV-2 multisystem inflammatory syndrome in children (MIS-C) and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS