Myogenic Regulatory Factor Expression is Downregulated Following Formoterol Stimulation in Thyroid Hormone Depleted Skeletal Muscle

In skeletal muscle (SKM), gene expression of transcription factors regulating myogenesis are dependent on Thyroid Hormone (TH) signal transduction. Expression of myogenic regulatory factors may be altered due to dysregulated TH metabolism, which may result in SKM dysfunction and intolerance to exercise in individuals with hypothyroidism. PURPOSE: Implement an in vitro model of hypothyroidism in SKM and determine the response of myogenic regulatory factor expression during several stages of myogenesis following TH depletion. Formoterol, an exercise mimetic, was also used to examine the effects of exercise signaling on myogenesis in TH depleted cells. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON), TH depleted cells (ThD), and TH depleted cells plus formoterol stimulation (ThD+F; 30nm for 3h). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6). Gene expression for myogenic regulatory factors (Myf5, MyoD, MyoG) was determined by qPCR. RESULTS: ThD decreased Myf5 at both Day 4 and Day 6 compared to control (P\u3c0.001). Myf5 was increased following ThD + F compared to ThD at Day 4 (P\u3c0.05). MyoD decreased following ThD at both Day 4 and Day 6 (P\u3c0.001). Further, MyoD was decreased following ThD + F at both Day 4 and Day 6 compared to ThD (P\u3c0.001). ThD had no effect on MyoG at Day 4 and Day 6; however, MyoG was decreased following ThD + F compared to ThD and control at both time points (P\u3c0.001). Data are expressed as mean ± SEM. CONCLUSION: TH depletion had no effect on MyoG but did reduce the expression of both Myf5 and MyoD at both Day 4 and Day 6. Additionally, ThD+F resulted in the lowest expression of MyoG and MyoD for both time points. These results indicate TH depletion and formoterol stimulation may inhibit myotube maturation

Locally Accessible Information of Multisite Quantum Ensembles Violates Monogamy

Locally accessible information is a useful information-theoretic physical quantity of an ensemble of multiparty quantum states. We find it has properties akin to quantum as well as classical correlations of single multiparty quantum states. It satisfies monotonicity under local quantum operations and classical communication. However we show that it does not follow monogamy, an important property usually satisfied by quantum correlations, and actually violates any such relation to the maximal extent. Violation is obtained even for locally indistinguishable, but globally orthogonal, multisite ensembles. The results assert that while single multiparty quantum states are monogamous with respect to their shared quantum correlations, ensembles of multiparty quantum states may not be so. The results have potential implications for quantum communication systems.Comment: 6 pages, RevTeX

Mitochondrial Biogenesis is Dysregulated in Thyroid Hormone Depleted Muscle Cells Despite Stimulatory Effects of Formoterol

Skeletal muscle (SKM) is an important regulator of metabolism and adaptations from exercise training influences mitochondrial function. Thyroid hormone (TH) is a regulator of SKM processes, including mitochondrial biogenesis. PURPOSE: To use an in vitro model of hypothyroidism to test the hypothesis that SKM cells will have dysregulated mitochondrial homeostasis. Additionally, the exercise mimetic, formoterol, was used to determine the effects of exercise signaling on mitochondrial biogenesis. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON), TH depleted cells (ThD), and TH depleted cells plus formoterol stimulation (ThD+F; 30nM for 3h). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6). Gene expression for Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha (PGC-1α), Mitochondrial Transcription Factor A (TFAM), and Nuclear Respiratory Factor 1 (NRF1) was determined by qPCR. Data was analyzed by repeated measures ANOVA. RESULTS: PGC-1α: D4 ThD was decreased compared to D4 ThD+F (-4.6); D4 ThD+F was increased compared to D4 CON (4.6); D6 CON was decreased compared to D6 ThD+F (-2.9); D6 ThD was decreased compared to D6 ThD+F (-3.7). TFAM: D4 ThD+F was greater than D4 CON (3.6); D4 ThD+F was greater than D6 ThD+F (3.6); D6 ThD was decreased compared to D6 CON (-0.55); D6 ThD+F was decreased compared to D6 CON (-0.63). NRF1: D4 ThD was decreased compared to D4 CON (-0.31); D4 ThD was greater than D4 ThD+F (0.36); D4 ThD was greater than D6 ThD (0.17); ThD+F was decreased compared to D4 CON (-0.67); D6 CON was decreased compared to D4 CON (-0.18); D6 ThD was decreased compared to D6 CON (-0.3); D6 ThD+F was decreased compared to D6 CON (-0.42). All reported differences are significant (p \u3c 0.05). Data are expressed as fold changes. CONCLUSION: ThD media resulted in reduced NRF1 signaling in both D4 and D6 with a subsequent decrease in D6 only for TFAM. Formoterol resulted in the expected stimulation of PGC-1α at both D4 and D6, but subsequent signaling for genes associated with mitochondrial biogenesis common to PGC-1α stimulation were lost as a result of TH depletion at D6 only for TFAM and both D4 and D6 for NRF1

Formoterol Stimulation In Vitro Influences Myogenic Regulatory Factors During Myogenesis in Human Skeletal Muscle Cells

The process of myogenesis within skeletal muscle (SKM) is essential for growth and repair and is coordinated via the expression of myogenic regulatory genes. Previous animal studies have reported that formoterol, a beta-adrenergic receptor agonist, has stimulating effects on genes related to SKM mitochondrial function and biogenesis, similar to effects found for exercise. Lesser known is the potential “exercise mimetic” influence that formoterol stimulation may have during the stages of myogenesis, especially in human SKM cells. PURPOSE: To investigate the effects of formoterol stimulation on expression of myogenic regulatory genes during myogenesis in human SKM cells. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON) and cells stimulated by 30nM formoterol for 3h prior to RNA extraction points (FORM). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6) (a cell culture model of investigating myogenesis). Gene expression for Myogenic factor 5 (Myf5), Myogenic differentiation 1(MyoD), and Myogenin (MyoG) was determined by qPCR. Data was analyzed using repeated measures ANOVA. RESULTS: Myf5: There was no change for either condition for D4. D6 CON was lower than D4 CON (-0.25). D6 FORM was greater than D4 FORM (0.65) and D6 CON (0.75). MyoD: D4 FORM was lower than D4 CON (-0.57). D6 FORM was greater than D4 FORM (0.85) and lower than D6 CON (-0.16). D6 CON was lower than D4 CON (-0.33). MyoG: D4 FORM was lower than D4 CON (-0.72). D6 CON was lower than D4 CON (-0.44). D6 FORM was lower than D6 CON (-0.24). All reported differences are significant (p \u3c 0.05). Data are expressed as fold changes. CONCLUSION: As expected, for the CON group, Myf5, MyoD, and MyoG expression all decreased from D4 mid-myogenesis to D6 terminal myogenesis, indicating finalization of the myogenic gene program. For the FORM group, Myf5 expression was elevated at D6 compared to CON while MyoG and MyoD expression was lower than CON for D4 and D6. The interpretation is that FORM stimulation increased stimulus of D4 myoblast proliferation and, thus, delayed initiation of differentiation. These results, coupled with other preliminary data from our lab showing increased mitochondrial biogenesis with this model of investigation, suggests that this exercise mimetic stimulation may cause shift in the cell towards bioenergetic preference rather than fusion of myotubes

The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident

Background: We report the first identified outbreak of cryptosporidiosis with Cryptosporidium cuniculus following a water quality incident in Northamptonshire, UK. Methods: A standardised, enhanced Cryptosporidium exposure questionnaire was administered to all cases of cryptosporidiosis after the incident. Stool samples, water testing, microscopy slides and rabbit gut contents positive for Cryptosporidium were typed at the Cryptosporidium Reference Unit, Singleton Hospital, Swansea. Results: Twenty-three people were microbiologically linked to the incident although other evidence suggests an excess of 422 cases of cryptosporidiosis above baseline. Most were adult females; unusually for cryptosporidiosis there were no affected children identified under the age of 5 years. Water consumption was possibly higher than in national drinking water consumption patterns. Diarrhoea duration was negatively correlated to distance from the water treatment works where the contamination occurred. Oocyst counts were highest in water storage facilities. Conclusions: This outbreak is the first caused by C. cuniculus infection to have been noted and it has conclusively demonstrated that this species can be a human pathogen. Although symptomatically similar to cryptosporidiosis from C. parvum or C. hominis, this outbreak has revealed some differences, in particular no children under 5 were identified and females were over-represented. These dissimilarities are unexplained although we postulate possible explanations

Exploring Campylobacter seasonality across Europe (2008-2016) using The European Surveillance System TESSy

Background: Campylobacteriosis is the most commonly reported food-borne infection in the European Union, with an annual number of cases estimated at around 9 million. In many countries, campylobacteriosis has a striking seasonal peak during early/ mid-summer. In the early 2000s, several publications reported on campylobacteriosis seasonality across Europe and associations with temperature and precipitation. Subsequently, many European countries have introduced new measures against this foodborne disease. Aim: To examine how the seasonality of campylobacteriosis varied across Europe from 2008–16, to explore associations with temperature and precipitation, and to compare these results with previous studies. We also sought to assess the utility of the European Surveillance System TESSy for cross-European seasonal analysis of campylobacteriosis. Methods: Ward’s Minimum Variance Clustering was used to group countries with similar seasonal patterns of campylobacteriosis. A two-stage multivariate meta-analysis methodology was used to explore associations with temperature and precipitation. Results: Nordic countries had a pronounced seasonal campylobacteriosis peak in mid-to late summer (weeks 29–32), while most other European countries had a less pronounced peak earlier in the year. The United Kingdom, Ireland, Hungary and Slovakia had a slightly earlier peak (week 24). Campylobacteriosis cases were positively associated with temperature and, to a lesser degree, precipitation. Conclusion: Across Europe, the strength and timing of campylobacteriosis peaks have remained similar to those observed previously. In addition, TESSy is a useful resource for cross-Euro-pean seasonal analysis of infectious diseases such as campylobacteriosis, but its utility depends upon each country’s reporting infrastructure

Cyclospora infection linked to travel to Mexico, June to September 2015.

Cyclospora cayetanensis was identified in 176 returned travellers from the Riviera Maya region of Mexico between 1 June and 22 September 2015; 79 in the United Kingdom (UK) and 97 in Canada. UK cases completed a food exposure questionnaire. This increase in reported Cyclospora cases highlights risks of gastrointestinal infections through travelling, limitations in Cyclospora surveillance and the need for improved hygiene in the production of food consumed in holiday resorts

A comparison of weather variables linked to infectious disease patterns using laboratory addresses and patient residence addresses

Background: To understand the impact of weather on infectious diseases, information on weather parameters at patient locations is needed, but this is not always accessible due to confidentiality or data availability. Weather parameters at nearby locations are often used as a proxy, but the accuracy of this practice is not known. Methods: Daily Campylobacter and Cryptosporidium cases across England and Wales were linked to local temperature and rainfall at the residence postcodes of the patients and at the corresponding postcodes of the laboratory where the patient’s specimen was tested. The paired values of daily rainfall and temperature for the laboratory versus residence postcodes were interpolated from weather station data, and the results were analysed for agreement using linear regression. We also assessed potential dependency of the findings on the relative geographic distance between the patient’s residence and the laboratory. Results: There was significant and strong agreement between the daily values of rainfall and temperature at diagnostic laboratories with the values at the patient residence postcodes for samples containing the pathogens Campylobacter or Cryptosporidium. For rainfall, the R-squared was 0.96 for the former and 0.97 for the latter, and for maximum daily temperature, the R-squared was 0.99 for both. The overall mean distance between the patient residence and the laboratory was 11.9 km; however, the distribution of these distances exhibited a heavy tail, with some rare situations where the distance between the patient residence and the laboratory was larger than 500 km. These large distances impact the distributions of the weather variable discrepancies (i.e. the differences between weather parameters estimated at patient residence postcodes and those at laboratory postcodes), with discrepancies up to ±10 °C for the minimum and maximum temperature and 20 mm for rainfall. Nevertheless, the distributions of discrepancies (estimated separately for minimum and maximum temperature and rainfall), based on the cases where the distance between the patient residence and the laboratory was within 20 km, still exhibited tails somewhat longer than the corresponding exponential fits suggesting modest small scale variations in temperature and rainfall. Conclusion: The findings confirm that, for the purposes of studying the relationships between meteorological variables and infectious diseases using data based on laboratory postcodes, the weather results are sufficiently similar to justify the use of laboratory postcode as a surrogate for domestic postcode. Exclusion of the small percentage of cases where there is a large distance between the residence and the laboratory could increase the precision of estimates, but there are generally strong associations between daily weather parameters at residence and laboratory

The Economic Resource Receipt of New Mothers

U.S. federal policies do not provide a universal social safety net of economic support for women during pregnancy or the immediate postpartum period but assume that employment and/or marriage will protect families from poverty. Yet even mothers with considerable human and marital capital may experience disruptions in employment, earnings, and family socioeconomic status postbirth. We use the National Survey of Families and Households to examine the economic resources that mothers with children ages 2 and younger receive postbirth, including employment, spouses, extended family and social network support, and public assistance. Results show that many new mothers receive resources postbirth. Marriage or postbirth employment does not protect new mothers and their families from poverty, but education, race, and the receipt of economic supports from social networks do

Environmental Suitability of Vibrio Infections in a Warming Climate: An Early Warning System

Background: Some Vibrio spp. are pathogenic and ubiquitous in marine waters with low to moderate salinity and thrive with elevated sea surface temperature (SST). Objectives: Our objective was to monitor and project the suitability of marine conditions for Vibrio infections under climate change scenarios. Methods: The European Centre for Disease Prevention and Control (ECDC) developed a platform (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover study of Swedish cases was conducted to ascertain the relationship between SST and Vibrio infection through a conditional logistic regression. Climate change projections for Vibrio infections were developed for Representative Concentration Pathway (RCP) 4.5 and RCP 8.5. Results: The ECDC Vibrio Map Viewer detected environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014 that were accompanied by a spike in cases and one death in Sweden. The estimated exposure–response relationship for Vibrio infections at a threshold of 16°C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2 wk; the estimated risk increased successively beyond this SST threshold. Climate change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a marked upward trend during the summer months and an increase in the relative risk of these infections in the coming decades. Conclusions: This platform can serve as an early warning system as the risk of further Vibrio infections increases in the 21st century due to climate change. https://doi.org/10.1289/EHP219