Mancha3D Code: Multipurpose Advanced Nonideal MHD Code for High-Resolution Simulations in Astrophysics.

The Mancha3D code is a versatile tool for numerical simulations of magnetohydrodynamic (MHD) processes in solar/stellar atmospheres. The code includes nonideal physics derived from plasma partial ionization, a realistic equation of state and radiative transfer, which allows performing high-quality realistic simulations of magnetoconvection, as well as idealized simulations of particular processes, such as wave propagation, instabilities or energetic events. The paper summarizes the equations and methods used in the Mancha3D (Multifluid (-purpose -physics -dimensional) Advanced Non-ideal MHD Code for High resolution simulations in Astrophysics 3D) code. It also describes its numerical stability and parallel performance and efficiency. The code is based on a finite difference discretization and a memory-saving Runge-Kutta (RK) scheme. It handles nonideal effects through super-time-stepping and Hall diffusion schemes, and takes into account thermal conduction by solving an additional hyperbolic equation for the heat flux. The code is easily configurable to perform different kinds of simulations. Several examples of the code usage are given. It is demonstrated that splitting variables into equilibrium and perturbation parts is essential for simulations of wave propagation in a static background. A perfectly matched layer (PML) boundary condition built into the code greatly facilitates a nonreflective open boundary implementation. Spatial filtering is an important numerical remedy to eliminate grid-size perturbations enhancing the code stability. Parallel performance analysis reveals that the code is strongly memory bound, which is a natural consequence of the numerical techniques used, such as split variables and PML boundary conditions. Both strong and weak scalings show adequate performance up to several thousands of processors (CPUs).

Future prospects for partially ionized solar plasmas: the prominence case.

Partially ionized plasmas (PIP) constitute an essential ingredient of our plasma universe. Historically, the physical effects associated with partial ionization were considered in astrophysical topics such as the interstellar medium, molecular clouds, accretion disks and, later on, in solar physics. PIP can be found in layers of the Sun's atmosphere as well as in solar structures embedded within it. As a consequence, the dynamical behaviour of these layers and structures is influenced by the different physical effects introduced by partial ionization. Here, rather than considering an exhaustive discussion of partially ionized effects in the different layers and structures of the solar atmosphere, we focus on solar prominences. The reason is that they represent a paradigmatic case of a partially ionized solar plasma, confined and insulated by the magnetic field, constituting an ideal environment to study the effects induced by partial ionization. We present the current knowledge about the effects of partial ionization in the global stability, mass cycle and dynamics of solar prominences. We revise the identified observational signatures of partial ionization in prominences. We conclude with prospects for PIP research in prominences, proposing the path for advancing in the prominence modelling and theory and using new and upcoming instrumentation. This article is part of the theme issue 'Partially ionized plasma of the solar atmosphere: recent advances and future pathways'.

Vitamin D and Skin Cancer: A Controversial Society. Literature Update and Review. / Vitamina D y cáncer cutáneo: una asociación controvertida. Actualización y revisión de la literatura.

Vitamin D (VD) deficiency has been associated with various tumors. However, the association between VD and skin cancer is controversial. Although in non-melanoma skin cancer, adequate or even high levels of VD can be associated with a higher risk of developing tumors, this could be biased by the direct association between sun exposure and VD levels. Regarding melanoma, results are contradictory. Most studies analyzed state that higher levels of VD could reduce the risk of melanoma, be associated with melanomas with better prognosis and with an enhanced antitumor response, and also with fewer adverse events associated with melanoma immunotherapy. However, prospective studies of adequate methodological quality are still needed to assess the association between VD levels and its supplementation and development/prognosis in skin cancer.

Salinity and host drive Ulva-associated bacterial communities across the Atlantic-Baltic Sea gradient.

The green seaweed Ulva is a model system to study seaweed-bacteria interactions, but the impact of environmental drivers on the dynamics of these interactions is little understood. In this study, we investigated the stability and variability of the seaweed-associated bacteria across the Atlantic-Baltic Sea salinity gradient. We characterized the bacterial communities of 15 Ulva sensu lato species along 2,000 km of coastline in a total of 481 samples. Our results demonstrate that the Ulva-associated bacterial composition was strongly structured by both salinity and host species (together explaining between 34% and 91% of the variation in the abundance of the different bacterial genera). The largest shift in the bacterial consortia coincided with the horohalinicum (5-8 PSU, known as the transition zone from freshwater to marine conditions). Low-salinity communities especially contained high relative abundances of Luteolibacter, Cyanobium, Pirellula, Lacihabitans and an uncultured Spirosomaceae, whereas high-salinity communities were predominantly enriched in Litorimonas, Leucothrix, Sulfurovum, Algibacter and Dokdonia. We identified a small taxonomic core community (consisting of Paracoccus, Sulfitobacter and an uncultured Rhodobacteraceae), which together contributed to 14% of the reads per sample, on average. Additional core taxa followed a gradient model, as more core taxa were shared between neighbouring salinity ranges than between ranges at opposite ends of the Atlantic-Baltic Sea gradient. Our results contradict earlier statements that Ulva-associated bacterial communities are taxonomically highly variable across individuals and largely stochastically defined. Characteristic bacterial communities associated with distinct salinity regions may therefore facilitate the host's adaptation across the environmental gradient.

CLASSICA: Validating artificial intelligence in classifying cancer in real time during surgery.

AIM: Treatment pathways for significant rectal polyps differ depending on the underlying pathology, but pre-excision profiling is imperfect. It has been demonstrated that differences in fluorescence perfusion signals following injection of indocyanine green (ICG) can be analysed mathematically and, with the assistance of artificial intelligence (AI), used to classify tumours endoscopically as benign or malignant. This study aims to validate this method of characterization across multiple clinical sites regarding its generalizability, usability and accuracy while developing clinical-grade software to enable it to become a useful method. METHODS: The CLASSICA study is a prospective, unblinded multicentre European observational study aimed to validate the use of AI analysis of ICG fluorescence for intra-operative tissue characterization. Six hundred patients undergoing transanal endoscopic evaluation of significant rectal polyps and tumours will be enrolled in at least five clinical sites across the European Union over a 4-year period. Video recordings will be analysed regarding dynamic fluorescence patterns centrally as software is developed to enable analysis with automatic classification to happen locally. AI-based classification and subsequently guided intervention will be compared with the current standard of care including biopsies, final specimen pathology and patient outcomes. DISCUSSION: CLASSICA will validate the use of AI in the analysis of ICG fluorescence for the purposes of classifying significant rectal polyps and tumours endoscopically. Follow-on studies will compare AI-guided targeted biopsy or, indeed, AI characterization alone with traditional biopsy and AI-guided local excision versus traditional excision with regard to marginal clearance and recurrence.

Short-term effects of air pollution and noise on emergency hospital admissions in Madrid and economic assessment.

INTRODUCTION: The aim of this study was to study the effect of air pollution and noise has on the population in Madrid Community (MAR) in the period 2013-2018, and its economic impact. METHODS: Time series study analysing emergency hospital admissions in the MAR due to all causes (ICD-10: A00-R99), respiratory causes (ICD-10: J00-J99) and circulatory causes (ICD-10: I00-I99) across the period 2013-2018. The main independent variables were mean daily PM2.5, PM10, NO2, 8-h ozone concentrations, and noise. We controlled for meteorological variables, Public Holidays, seasonality, and the trend and autoregressive nature of the series, and fitted generalised linear models with a Poisson regression link to ascertain the relative risks and attributable risks. In addition, we made an economic assessment of these hospitalisations. RESULTS: The following associations were found: NO2 with admissions due to natural (RR: 1.007, 95% CI: 1.004-1.011) and respiratory causes (RR: 1.012, 95% CI: 1.005-1.019); 8-h ozone with admissions due to natural (RR: 1.049, 95% CI: 1.014-1.046) and circulatory causes (RR: 1.088, 95% CI: 1.039-1.140); and diurnal noise (LAeq7-23h) with admissions due to natural (RR: 1.001, 95% CI: 1.001-1.002), respiratory (RR: 1.002, 95% CI: 1.001-1.003) and circulatory causes (RR: 1.003, 95% CI: 1.002-1.005). Every year, a total of 8246 (95% CI: 4580-11,905) natural-cause admissions are attributable to NO2, with an estimated cost of close on €120 million and 5685 (95% CI: 2533-8835) attributed to LAeq7-23h with an estimated cost of close on €82 million. CONCLUSIONS: Nitrogen dioxide, ozone and noise are the main pollutants to which a large number of hospitalisations in the MAR are attributed, and are thus responsible for a marked deterioration in population health and high related economic impact.

Short-term impact of noise, other air pollutants and meteorological factors on emergency hospital mental health admissions in the Madrid region.

BACKGROUND: A number of environmental factors, such as air pollution, noise in urbanised settings and meteorological-type variables, may give rise to important effects on human health. In recent years, many studies have confirmed the relation between various mental disorders and these factors, with a possible impact on the increase in emergency hospital admissions due to these causes. The aim of this study was to analyse the impact of a range of environmental factors on daily emergency hospital admissions due to mental disorders in the Madrid Autonomous Region (MAR), across the period 2013-2018. METHODOLOGY: Longitudinal ecological time series study analysed by Generalised Linear Models with Poisson regression, with the dependent variable being daily Emergency Hospital Mental Health Admissions (EHMHA) in the MAR, and the independent variable being mean daily concentrations of chemical pollutants, noise levels and meteorological variables. RESULTS: EHMHA were related statistically significantly in the short term with diurnal noise levels. Relative risks (RRs) for total admissions due to mental disorders and self-inflicted injuries, in the case of diurnal noise was RR: 1.008 95%CI (1.003 1.013). Admissions attributable to diurnal noise account for 5.5% of total admissions across the study period. There was no association between hospital admissions and chemical air pollution. CONCLUSION: Noise is a variable that shows a statistically significant short-term association with EHMHA across all age groups in the MAR region. The results of this study may serve as a basis for drawing up public health guidelines and plans, which regard these variables as risk factors for mental disorders, especially in the case of noise, since this fundamentally depends on anthropogenic activities in highly urbanised areas with high levels of traffic density.

Lung ultrasound and postoperative follow-up of congenital diaphragmatic hernia.

Lung ultrasound (LU) has emerged as a valuable tool for assessing pulmonary aeration noninvasively, rapidly, and reliably in different neonatal conditions. However, its role in the preoperative and postoperative evaluation in congenital diaphragmatic hernia (CDH) is still poorly analyzed. We present a cohort of 8 patients diagnosed with CDH who underwent lung ultrasound examinations at various time points before and after surgical correction. The lung ultrasound patterns were compared between two groups: mechanical ventilation ≤ 7 days (MV ≤ 7) and mechanical ventilation > 7 days (MV > 7). The ultrasound findings were also compared to CT scans and chest X-ray images to assess its diagnostic capacity for identifying postoperative complications: pneumothorax, pleural effusion, and pneumonia. Group MV ≤ 7 exhibited a normal pattern even at 48 h postsurgery, while group MV > 7 presented interstitial or alveolointerstitial pattern in both lungs for prolonged periods (2-3 weeks). Furthermore, contralateral LU pattern may be predictive of respiratory evolution.  Conclusion: Lung ultrasound is a valuable tool for evaluating the progressive reaeration of the lung following surgical correction in CDH patients. It demonstrates the ability to diagnose common postoperative complications without the need for radiation exposure while offering the advantages of quick and serial assessments. These findings highlight the potential of lung ultrasound as an effective alternative to conventional imaging methods in the management of CDH. What is Known: • Lung ultrasound evaluates lung aeration and predicts respiratory outcomes in neonatal patients. What is New: • Lung ultrasound is useful in the postsurgical management of congenital diaphragmatic hernia patients, detecting reaeration and respiratory complications.

Analysis of vulnerability to heat in rural and urban areas in Spain: What factors explain Heat's geographic behavior?

INTRODUCTION: There is currently little knowledge and few published works on the subject of vulnerability to heat in rural environments at the country level. Therefore, the objective of this study was to determine whether rural areas are more vulnerable to extreme heat than urban areas in Spain. This study aimed to analyze whether a pattern of vulnerability depends on contextual, environmental, demographic, economic and housing variables. METHODS: An ecological, longitudinal and retrospective study was carried out based on time series data between January 01, 2000 and December 31, 2013 in 42 geographic areas in 10 provinces in Spain. We first analyzed the functional relationship between the mortality rate per million inhabitants and maximum daily temperature (Tmax). We then determined the summer temperature threshold (Pthreshold) (June-September) at which increases in mortality are produced that are attributable to heat. In a second phase, based on Pthreshold, a vulnerability variable was calculated, and its distribution was analyzed using mixed linear models from the Poisson family (link = log). In these models, the dependent variable was vulnerability, and the independent variables were exposure to high temperatures, aridity of the climate, deprivation index, percentage of people over age 65, rurality index, percentage of housing built prior to 1980 and condition of dwellings. RESULTS: Rurality was a protective factor, and vulnerability in urban areas was six times greater. In contrast, risk factors included aridity (RR = 5.89 (2.26 15.36)), living in cool summer zones (2.69 (1.23, 5.91)), poverty (4.05 (1.91 8.59)) and the percentage of dysfunctional housing (1.13 (1.04 1.24)). CONCLUSIONS: Rural areas are less vulnerable to extreme heat than the urban areas analyzed. Also, population groups with worse working conditions and higher percentages of dwellings in poor conditions are more vulnerable.

Gender differences in adaptation to heat in Spain (1983-2018).

In Spain the average temperature has increased by 1.7 °C since pre-industrial times. There has been an increase in heat waves both in terms of frequency and intensity, with a clear impact in terms of population health. The effect of heat waves on daily mortality presents important territorial differences. Gender also affects these impacts, as a determinant that conditions social inequalities in health. There is evidence that women may be more susceptible to extreme heat than men, although there are relatively few studies that analyze differences in the vulnerability and adaptation to heat by sex. This could be related to physiological causes. On the other hand, one of the indicators used to measure vulnerability to heat in a population and its adaptation is the minimum mortality temperature (MMT) and its temporal evolution. The aim of this study was to analyze the values of MMT in men and women and its temporal evolution during the 1983-2018 period in Spain's provinces. An ecological, longitudinal retrospective study was carried out of time series data, based on maximum daily temperature and daily mortality data corresponding to the study period. Using cubic and quadratic fits between daily mortality rates and the temperature, the minimum values of these functions were determined, which allowed for determining MMT values. Furthermore, we used an improved methodology that provided for the estimation of missing MMT values when polynomial fits were inexistent. This analysis was carried out for each year. Later, based on the annual values of MMT, a linear fit was carried out to determine the rate of evolution of MMT for men and for women at the province level. Average MMT for all of Spain's provinces was 29.4 °C in the case of men and 28.7 °C in the case of women. The MMT for men was greater than that of women in 86 percent of the total provinces analyzed, which indicates greater vulnerability among women. In terms of the rate of variation in MMT during the period analyzed, that of men was 0.39 °C/decade, compared to 0.53 °C/decade for women, indicating greater adaptation to heat among women, compared to men. The differences found between men and women were statistically significant. At the province level, the results show great heterogeneity. Studies carried out at the local level are needed to provide knowledge about those factors that can explain these differences at the province level, and to allow for incorporating a gender perspective in the implementation of measures for adaptation to high temperatures.

Methylene Blue functionalized carbon nanodots combined with different shape gold nanostructures for sensitive and selective SARS-CoV-2 sensing.

The development of DNA-sensing platforms based on new synthetized Methylene Blue functionalized carbon nanodots combined with different shape gold nanostructures (AuNs), as a new pathway to develop a selective and sensitive methodology for SARS-CoV-2 detection is presented. A mixture of gold nanoparticles and gold nanotriangles have been synthetized to modify disposable electrodes that act as an enhanced nanostructured electrochemical surface for DNA probe immobilization. On the other hand, modified carbon nanodots prepared a la carte to contain Methylene Blue (MB-CDs) are used as electrochemical indicators of the hybridization event. These MB-CDs, due to their structure, are able to interact differently with double and single-stranded DNA molecules. Based on this strategy, target sequences of the SARS-CoV-2 virus have been detected in a straightforward way and rapidly with a detection limit of 2.00 aM. Moreover, this platform allows the detection of the SARS-CoV-2 sequence in the presence of other viruses, and also a single nucleotide polymorphism (SNPs). The developed approach has been tested directly on RNA obtained from nasopharyngeal samples from COVID-19 patients, avoiding any amplification process. The results agree well with those obtained by RT-qPCR or reverse transcription quantitative polymerase chain reaction technique.

Nitrogen isotopic discrimination as a biomarker of between-cow variation in the efficiency of nitrogen utilization for milk production: A meta-analysis.

Estimating the efficiency of N utilization for milk production (MNE) of individual cows at a large scale is difficult, particularly because of the cost of measuring feed intake. Nitrogen isotopic discrimination (Δ15N) between the animal (milk, plasma, or tissues) and its diet has been proposed as a biomarker of the efficiency of N utilization in a range of production systems and ruminant species. The aim of this study was to assess the ability of Δ15N to predict the between-animal variability in MNE in dairy cows using an extensive database. For this, 20 independent experiments conducted as either changeover (n = 14) or continuous (n = 6) trials were available and comprised an initial data set of 1,300 observations. Between-animal variability was defined as the variation observed among cows sharing the same contemporary group (CG; individuals from the same experimental site, sampling period, and dietary treatment). Milk N efficiency was calculated as the ratio between mean milk N (grams of N in milk per day) and mean N intake (grams of N intake per day) obtained from each sampling period, which lasted 9.0 ± 9.9 d (mean ± SD). Samples of milk (n = 604) or plasma (n = 696) and feeds (74 dietary treatments) were analyzed for natural 15N abundance (δ15N), and then the N isotopic discrimination between the animal and the dietary treatment was calculated (Δ15n = δ15Nanimal - δ15Ndiet). Data were analyzed through mixed-effect regression models considering the experiment, sampling period, and dietary treatment as random effects. In addition, repeatability estimates were calculated for each experiment to test the hypothesis of improved predictions when MNE and Δ15N measurements errors were lower. The considerable protein mobilization in early lactation artificially increased both MNE and Δ15N, leading to a positive rather than negative relationship, and this limited the implementation of this biomarker in early lactating cows. When the experimental errors of Δ15N and MNE decreased in a particular experiment (i.e., higher repeatability values), we observed a greater ability of Δ15N to predict MNE at the individual level. The predominant negative and significant correlation between Δ15N and MNE in mid- and late lactation demonstrated that on average Δ15N reflects MNE variations both across dietary treatments and between animals. The root mean squared prediction error as a percentage of average observed value was 6.8%, indicating that the model only allowed differentiation between 2 cows in terms of MNE within a CG if they differed by at least 0.112 g/g of MNE (95% confidence level), and this could represent a limitation in predicting MNE at the individual level. However, the one-way ANOVA performed to test the ability of Δ15N to differentiate within-CG the top 25% from the lowest 25% individuals in terms of MNE was significant, indicating that it is possible to distinguish extreme animals in terms of MNE from their N isotopic signature, which could be useful to group animals for precision feeding.

Coral diversity matches marine park zonation but not economic value of coral reef sites at St. Eustatius, eastern Caribbean.

Stony corals play a key role in the marine biodiversity of many tropical coastal areas as suppliers of substrate, food and shelter for other reef organisms. Therefore, it is remarkable that coral diversity usually does not play a role in the planning of protected areas in coral reef areas. In the present study we examine how stony coral diversity patterns relate to marine park zonation and the economic value of reefs around St. Eustatius, a small island in the eastern Caribbean, with fisheries and tourism as important sources of income. The marine park contains two no-take reserves. A biodiversity survey was performed at 39 sites, 24 inside the reserves and 15 outside; 22 had a maximum depth >18 m and 17 were shallower. Data on economic value per site were obtained from the literature. Corals were photographed for the verification of identifications made in the field. Coral species richness (n = 49) was highest in the no-take reserves and species composition was mainly affected by maximum depth. No distinct relation is observed between coral diversity and fishery value or total economic value. Based on the outcome of this study we suggest that in future designs of marine park zonation in reef areas, coral diversity should be taken into consideration. This is best served by including reef areas with a continuous depth gradient from shallow flats to deep slopes.

A statistical evaluation of associations between reproductive performance and milk composition and animal factors on grazing dairy cows in two New Zealand dairy farms.

AIMS: To determine if milk composition, milk yield, live weight, live weight change, breed and heterosis are associated with reproductive performance in dairy cows from two dairy farms under New Zealand grazing conditions. METHODS: Milk composition was determined in herd tests from 205 Holstein-Friesian (F), 77 Jersey (J) and 351 F × J crossbred cows from two Massey University dairy herds in the 2016 and 2017 production seasons. Mating occurred from October to December in each production season. The start of breeding to first service (SBFS), start of breeding to conception (SBCO), submission rate at 21 days (SR21), pregnancy rate at 21 (PR21) and 42 days (PR42) were calculated for each cow. These traits were analysed using mixed linear models that included fixed effects for herd, production season, regression coefficients of deviation from median calving date, lactation number, proportion of F, F × J heterosis, energy-corrected milk yield (ECMY), percentages of fat, protein and lactose, milk urea nitrogen (MUN), live weight and change in live weight, with random effects for cow and residual error. The variables with binomial distribution were analysed using logistic regression. RESULTS: Deviation from the herd's median calving date had a significant effect (p < 0.05) on all reproductive traits. Proportion of F was significant (p = 0.022) on PR21, and F × J heterosis effects were significant on PR21 (p = 0.049) and PR42 (p = 0.046). F cows had 17.8% higher PR21 than J cows, and F × J cows had higher reproductive performance than the mean of the two purebreeds. ECMY was negatively associated with SBFS (p = 0.001) and SBCO (p = 0.001) and positively associated with PR21 (p = 0.002) and PR42 (p = 0.001). Protein percentage was positively associated (p < 0.05) with PR21 and PR42, whereas lactose percentage was negatively associated (p < 0.05) with PR21 and PR42. Cows gaining live weight were more likely to become pregnant within 21 days of the start of breeding (p = 0.020). Milk urea nitrogen was negatively associated (p = 0.042) with SR21. CONCLUSIONS AND CLINICAL RELEVANCE: This study confirms that breed, heterosis, ECMY, protein and lactose percentages, live weight change and calving date are associated with the reproductive performance of grazing cows. Results from this study contrast with the historical antagonism between milk production and reproductive performance in dairy cattle, demonstrating that well managed cows can achieve high levels of production and good reproductive performance. MUN was not associated with reproductive performance traits, except with SR21.

Biases in bulk: DNA metabarcoding of marine communities and the methodology involved.

With the growing anthropogenic pressure on marine ecosystems, the need for efficient monitoring of biodiversity grows stronger. DNA metabarcoding of bulk samples is increasingly being implemented in ecosystem assessments and is more cost-efficient and less time-consuming than monitoring based on morphology. However, before raw sequences are obtained from bulk samples, a profound number of methodological choices must be made. Here, we critically review the recent methods used for metabarcoding of marine bulk samples (including benthic, plankton and diet samples) and indicate how potential biases can be introduced throughout sampling, preprocessing, DNA extraction, marker and primer selection, PCR amplification and sequencing. From a total of 64 studies evaluated, our recommendations for best practices include to (a) consider DESS as a fixative instead of ethanol, (b) use the DNeasy PowerSoil kit for any samples containing traces of sediment, (c) not limit the marker selection to COI only, but preferably include multiple markers for higher taxonomic resolution, (d) avoid touchdown PCR profiles, (e) use a fixed annealing temperature for each primer pair when comparing across studies or institutes, (f) use a minimum of three PCR replicates, and (g) include both negative and positive controls. Although the implementation of DNA metabarcoding still faces several technical complexities, we foresee wide-ranging advances in the near future, including improved bioinformatics for taxonomic assignment, sequencing of longer fragments and the use of whole-genome information. Despite the bulk of biases involved in metabarcoding of bulk samples, if appropriate controls are included along the data generation process, it is clear that DNA metabarcoding provides a valuable tool in ecosystem assessments.

Analysis of the impact of heat waves on daily mortality in urban and rural areas in Madrid.

The objective of this study was to analyze and compare the effect of high temperatures on daily mortality in the urban and rural populations in Madrid. Data were analyzed from municipalities in Madrid with a population of over 10,000 inhabitants during the period from January 1, 2000 to December 31, 2020. Four groups were generated: Urban Metropolitan Center, Rural Northern Mountains, Rural Center, and Southern Rural. The dependent variable used was the rate of daily mortality due to natural causes per million inhabitants (CIE-X: A00-R99) between the months of June and September for the period. The primary independent variable was maximum daily temperature. Social and demographic "context variables" were included: population >64 years of age (%), deprivation index and housing indicators. The analysis was carried out in three phases: 1) determination of the threshold definition temperature of a heat wave (Tumbral) for each study group; 2) determination of relative risks (RR) attributable to heat for each group using Poisson linear regression (GLM), and 3) calculation of odds ratios (OR) using binomial family GLM for the frequency of the appearance of heat waves associated with context variables. The resulting percentiles (for the series of maximum daily temperatures for the summer months) corresponding to Tthreshold were: 74th percentile for Urban Metropolitan Center, 76th percentile for Southern Rural, 83rd for Rural Northern Mountains and 98th percentile for Center Rural (98). Greater vulnerability was found for the first two. In terms of context variables that explained the appearance of heat waves, deprivation index level, population >64 years of age and living in the metropolitan area were found to be risk factors. Rural and urban areas behaved differently, and socioeconomic inequality and the composition of the population over age 64 were found to best explain the vulnerability of the Rural Center and Southern Rural zones.

The influence of high-density lipoprotein (HDL) and HDL subfractions on insulin secretion and cholesterol efflux in pancreatic derived ß-cells.

BACKGROUND: High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the ß-cell line MIN-6. METHODS: We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line. RESULTS: Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux. CONCLUSIONS: HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

The -514C>T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans.

PURPOSE: Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in the LIPC gene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588) LIPC gene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk. METHODS: Mediation analysis was used to assess the direct and indirect effects of the -514C>T LIPC gene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>T LIPC variant on the promoter activity of a reporter gene in the HepG2 cell line. RESULTS: Direct effects show that the -514C>T LIPC polymorphism is significantly associated with increased HDL-C plasma levels (ß = 0.03; p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (ß = - 0.03; p < 0.001). Marginal direct association between -514C>T and T2D was found (ß = 0.08; p = 0.06). Variables directly influencing T2D status were European ethnicity (ß = - 7.20; p < 0.001), age (ß = 0.04; p < 0.001), gender (ß = - 0.15; p = 0.017) and HDL-C (ß = - 1.07; p < 0.001). In addition, we found that the -514C>T variant decreases the activity of LIPC promoter by 90% (p < 0.001). CONCLUSIONS: The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>T LIPC gene variant and T2D risk in the Mexican population.

R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.

The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis.

OBJECTIVE: Metabolic syndrome is characterized by obesity, hyperglycemia, hypertension, insulin resistance, and dyslipidemia. Metabolic syndrome is associated with osteoarthritis (OA), but it is unclear if the association is attributable to increased mechanical loading on joints caused by obesity or other aspects of metabolic syndrome. Here we examined the effects of altered metabolism, obesity, and the gut microbiome on load-induced OA. DESIGN: Cartilage damage was induced through cyclic compressive loading in four groups of adult male mice: Toll-like receptor-5 deficient (TLR5KO) mice that develop metabolic syndrome due to alterations in the gut microbiome, TLR5KO mice submitted to chronic antibiotics to prevent metabolic syndrome (TLR5KOΔMicrobiota), C57BL/6J mice fed a high fat diet to cause obesity (HFD), and untreated C57BL/6J mice (WT). Loading was applied for 2 weeks (n = 10-11/group) or 6 weeks (n = 10-11/group). RESULTS: After 2 weeks of loading, cartilage damage (OARSI score) was not different among groups. After 6 weeks of loading, HFD mice had increased load-induced cartilage damage, while TLR5KO mice had cartilage damage comparable to WT mice. TLR5KOΔMicrobiota mice had less cartilage damage than other groups. HFD mice had elevated serum inflammatory markers. Each group had a distinct gut microbiome composition. CONCLUSIONS: Severe obesity increased load-induced cartilage damage, while milder changes in adiposity/metabolic syndrome seen in TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on cartilage damage depend on the duration of mechanical loading. Lastly, reduced cartilage damage in the TLR5KOΔMicrobiota mice suggests that the gut microbiome may influence cartilage pathology.