Adenylate kinase 9 is essential for sperm function and male fertility in mammals.

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.

Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine.

INTRODUCTION: The Angiotensin-Converting Enzyme 2 (ACE2) is the main receptor of the SARS-CoV-2. There is contradictory evidence on how the exposure to nicotine may module the concentration of soluble ACE2 (sACE2). The aim of this study was to assess the association between nicotine and sACE2 concentrations in saliva samples. METHODS: Pooled analysis performed with data retrieved from two studies (n = 634 and n = 302). Geometric mean (GM) concentrations of sACE2, both total and relative to the total amount of protein in the sample, were compared according to sociodemographic variables and variables associated to nicotine. Multivariable linear regression models were fitted to explore the associations of sACE2 with nicotine adjusting for sex, age and body mass index. Spearman's rank-correlation coefficients were estimated between the concentrations of nicotine and cotinine, and pack-years, the concentration of relative sACE2 and the isoforms of sACE2. RESULTS: We observed a significant increase of 0.108‰ and 0.087 ng/µl in the relative and absolute salivary sACE2 GM concentrations, respectively, between the lowest and highest nicotine levels. Similar results were observed for cotinine. These associations did not change in the multivariable linear models. There was a low correlation of nicotine and cotinine concentration with the concentration of relative salivary sACE2 (rs = 0.153 and rs = 0.132, respectively), pack-years (rs = 0.222 and rs = 0.235, respectively) and with the concentration of isoform 40 KDa (rs = 0.193 and rs = 0.140, respectively). CONCLUSION: Salivary nicotine concentration seems to be limitedly associated with the concentration of sACE2.

Galectin-1 induces gene and protein expression related to maternal-conceptus immune tolerance in bovine endometrium†.

Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic cluster of differentiation 11c (CD11c) positive dendritic cells, increased anti-inflammatory interleukin (IL)-10, and activation of forkhead box P3 (FOXP3) positive regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-conceptus immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3, and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7, and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10, and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

Association between Leisure Screen Time and Emotional and Behavioral Problems in Spanish Children.

OBJECTIVE: To assess the relation between leisure screen time and emotional and behavioral problems in Spanish children aged 4-14 years. STUDY DESIGN: This cross-sectional study used a representative sample of children aged 4-14 years included in the 2017 Spanish National Health Survey (n = 4073). Emotional and behavioral problems of children were assessed through the parent-report Strengths and Difficulties Questionnaire. Daily leisure screen time in minutes was categorized as 0-59, 60-119, 120-179, and ≥180. We calculated adjusted prevalence ratios (aPR) and their 95% CIs of being at risk of developing emotional and behavioral problems. Associations were adjusted for potential confounding variables. RESULTS: Children spending 180 minutes or more of daily leisure screen time compared with children spending less than 1 hour were more likely to be at risk of developing emotional and behavioral problems: aPR≥180: 2.19 (95% CI 1.53-3.14), emotional symptomology: aPR≥180: 2.09 (95% CI 1.37-3.18), conduct problems aPR≥180: 1.85 (95% CI 1.34-2.54), peer problems aPR≥180: 1.78 (95% CI 1.15-2.75), and to behave less prosocially: aPR≥180: 2.20 (95% CI 1.43-3.37). CONCLUSIONS: We have found significant associations between daily leisure screen time and emotional and behavioral problems in Spanish children between 6 and 14 years of age. However, these findings should be confirmed in cohort studies, so institutions might consider including screen time as a new risk factor for children.

Conceptus metabolomic profiling reveals stage-specific phenotypes leading up to pregnancy recognition in cattle†.

Reproductive efficiency in livestock is a major driver of sustainable food production. The poorly understood process of ruminant conceptus elongation (a) prerequisites maternal pregnancy recognition, (b) is essential to successful pregnancy establishment, and (c) coincides with a period of significant conceptus mortality. Conceptuses at five key developmental stages between Days 8-16 were recovered and cultured in vitro for 6 h prior to conditioned media analysis by untargeted ultrahigh-performance liquid chromatography tandem mass spectroscopy. This global temporal biochemical interrogation of the ex situ bovine conceptus unearths two antithetical stage-specific metabolic phenotypes during tubular (metabolically retentive) vs. filamentous (secretory) development. Moreover, the retentive conceptus phenotype on Day 14 coincides with an established period of elevated metabolic density in the uterine fluid of heifers with high systemic progesterone-a model of accelerated conceptus elongation. These data, combined, suggest a metabolic mechanism underpinning conceptus elongation, thereby enhancing our understanding of the biochemical reciprocity of maternal-conceptus communication, prior to maternal pregnancy recognition.

Association of screen time and sleep duration among Spanish 1-14 years old children.

BACKGROUND: Due to the change in screen time usage in the last decade, there is needed to add more evidence about the relationship of screen time and sleep duration. OBJECTIVE: To assess the association between screen time and sleep duration among Spanish children between 1 and 14 years old. METHODS: We used data from the 2017 Spanish National Health survey, conducted on a representative sample of the Spanish population. We categorised daily leisure screen time as 0-59, 60-119, 120-179, and ≥180 minutes. We classified sleep duration, depending on the age, as proper sleep duration and short sleep duration. We calculated unadjusted, and adjusted prevalence ratio (PR) and 95% confidence interval (CI) of short sleep duration according to daily leisure screen time after adjusting for potential confounders. PR's were derived from fitting generalised linear models with Poisson distribution and robust variance. RESULTS: Of the 5517 Spanish children aged 1-14 years, 44.3% spent 120 minutes or more of daily leisure screen time and 23.6% had short sleep duration. 24.5% and 28.2% of children spending between 120 and 179 minutes and exceeding 180 minutes of daily leisure screen time suffered short sleep duration, respectively. In the adjusted model, higher patterns of daily leisure screen time were associated with short sleep duration: adjusted PR120-179  = 1.34 (95% CI 1.18, 1.54) and adjusted PR≥180  = 1.48 (95% CI 1.27, 1.73). CONCLUSIONS: Around one out of four Spanish children between 1 and 14 years old, exceeding 120 minutes of daily leisure screen time, had short sleep duration. More scientific research is needed for institutions to work on providing novel healthcare programmes that consider these new determinants of child health.

Third-hand exposure at homes: Assessment using salivary cotinine.

BACKGROUND/OBJECTIVES: While exposure to secondhand smoke (SHS) is a well-established problem, exposure to third-hand smoke (THS) is scanty known and needs to be studied. The objective of this work is to characterize salivary cotinine concentrations among people who self-reported exposure to SHS and THS at home. METHODS: Cross-sectional study of a representative sample (n = 736) of the adult population (≥16 years) from the city of Barcelona carried out in 2013-2014. A questionnaire on tobacco use and passive exposure was administered, and a saliva sample was collected for cotinine determination. For this study, the information of the non-smoker participants who provided saliva sample (n = 519) was used. The geometric means (GM) and geometric standard deviations (GSD) of the cotinine concentration were compared according to the type of self-reported exposure at home: (1) Not exposed to SHS or THS; (2) Exposed to SHS and THS; and (3) Only exposed to THS. We used log-linear models to compare the cotinine concentration of each exposed group with respect to the unexposed group, adjusting for sex, age, educational level, and tobacco exposure in other settings. RESULTS: The GM of the salivary cotinine concentration was 0.34 ng/ml (GSD = 0.16) among individuals reporting SHS and THS exposure, 0.22 ng/ml (GSD = 0.15) among those reporting only THS exposure and 0.11 ng/ml (GSD = 0.04) among those who declared not to be exposed to SHS nor THS (p-value for trend <0.001). The regression model showed a statistically significant increase in cotinine concentration among those exposed to SHS and THS (188% higher, 95% CI: 153%; 223%), and only exposed to THS (106% higher, IC95. %: 74.5%; 137.0%) when comparing with the unexposed group. No statistically significant differences in cotinine concentration were observed between those exposed to SHS and THS compared to the THS group (-25.8%, 95% CI: -69.5%; 17.9%). CONCLUSIONS/RECOMMENDATIONS: People exposed to third-hand smoke at home had quantifiable cotinine levels in saliva. No differences in cotinine levels were found between those exposed to second-hand and third-hand smoke at home. The reduction of exposure to third-hand smoke at home should be put into the agenda of tobacco control.

How do infants and toddlers sleep in Spain? A cross-sectional study.

There is limited information on sleep patterns among infants and toddlers in Spain. The aim of this study was to assess sleep patterns in children three to 36 months of age in Spain. A cross-sectional study was conducted between February 2017 and February 2018. Sociodemographic data and sleep variables were collected using an expanded version of the validated Spanish version of the brief infant sleep questionnaire. A total of 1,404 parental reports on children (725 males; 679 females) with a mean age of 18.8 ± 9.5 months were collected. Parents who perceived their child's sleep as problematic (39% of our sample) reported fewer sleep hours (median 9 versus 10 h), more night awakenings (median 2 versus 1), and longer periods of nocturnal awakenings (median 0.5 versus 0.08 min) (p < 0.001). Parental presence at the time of sleep onset and later and irregular bedtime routines were significantly associated with a reduction in total sleep time, longer sleep latency, and disruptive night awakenings (p < 0.001). These findings highlight the need for further studies to assess how to improve sleep patterns as a relevant modifiable lifestyle factor.Conclusion: A substantial percentage of the population perceived that their children slept poorly, which was evident in a variety of sleep patterns, including sleep duration and sleep quality. What is known: • Previous research has established that sleep difficulties among pediatric population affect up to 30% of all children and up to 20-30% of infants and toddlers. • A positive relationship between less parental bedtime involvement and sleep consolidation in infants and toddlers has been established. What is new: • More than a third of Spanish parents perceived their infants and toddlers sleep as problematic and their children reportedly have shorter night sleep hours, more night awakenings, and longer periods of nocturnal awakenings. • Later and irregular parental bedtime routines were associated with worst infants and toddlers sleep.

Role of reproductive fluids and extracellular vesicles in embryo–maternal interaction during early pregnancy in cattle.

The coordinated interaction between the developing embryo and the maternal reproductive tract is essential for the establishment and maintenance of pregnancy in mammals. An early cross-talk is established between the oviduct/uterus and the gametes and embryo. This dialogue will shape the microenvironment in which gamete transport, fertilisation, and early embryonic development occur. Due to the small size of the gametes and the early embryo relative to the volume of the oviductal and uterine lumina, collection of tissue and fluid adjacent to these cells is challenging in cattle. Thus, the combination of in vivo and in vitro models seems to be the most appropriate approach to better understand this fine dialogue. In this respect, the aim of this review is to summarise the recent findings in relation to gamete/embryo-maternal interaction during the pre-elongation period.

A cost-effectiveness analysis comparing a conventional mechanical needle to a radiofrequency device for transseptal punctures.

INTRODUCTION: Transseptal puncture is an integral step in various catheter-based cardiac procedures and can be performed with either the conventional mechanical needle or an FDA-cleared device utilizing radiofrequency (RF) energy. Although a previous randomized trial suggested that the RF transseptal device may be faster and more often successful, the increased equipment costs may dissuade operators from routine use. This analysis compares the cost-effectiveness of the mechanical needle to the RF device during pulmonary vein isolation. METHODS: The rates of successful transseptal punctures for each device and transseptal-related complications were determined from the peer-reviewed medical literature. Procedural, equipment, and complication costs were obtained from peer-reviewed medical literature and the Healthcare Cost and Utilization Project. The effectiveness was defined as the probability of 30-day survival following a successful transseptal puncture. Monte Carlo probabilistic analyses tested variable effects of costs and complication rates on the incremental cost-effectiveness ratio. RESULTS: The 30-day effectiveness of the RF device vs the mechanical needle was 99.7% and 98.8%, respectively. After accounting for all costs of performing a single transseptal puncture, the cost at 30 days associated with the RF device was $41 less than the mechanical needle ($21 096 vs $21 137). The RF device was similarly dominant to the mechanical needle in double transseptal puncture scenarios. Finally, the RF device was more cost-effective than the mechanical needle at any willingness-to-pay in Monte Carlo probabilistic sensitivity analyses. CONCLUSIONS: Despite greater equipment costs, the RF device costs less and provides better effectiveness at 30 days than the conventional mechanical needle.

Location relative to the corpus luteum affects bovine endometrial response to a conceptus.

In cattle, embryo transfer into the uterine horn contralateral to the corpus luteum results in a higher incidence of pregnancy loss compared to transfer into the ipsilateral horn. We have previously reported temporal changes in the endometrial transcriptome during the estrous cycle which differ between uterine horns. The objective of this study was to compare the transcriptomic response of endometrium from the ipsilateral and contralateral horns to an elongating conceptus. Cross-bred beef heifers (n = 16) were synchronized and either used to generate day 14 conceptuses following the transfer of in vitro-produced blastocysts or to obtain day 14 endometrial explants. Conceptuses were recovered on day 14 by post-mortem uterine flushing, placed individually on top of explants collected from the ipsilateral (IPSI-D14) or the contralateral (CONTRA-D14) uterine horn of cyclic heifers, and co-cultured for 6 h. The response to a conceptus was markedly different between uterine horns, with 61 and 239 differentially expressed genes (DEGs; false discovery rate <0.05) in the ipsilateral and contralateral horns, respectively, compared to their controls. Direct comparison between IPSI-D1 and CONTRA-D14 revealed 32 DEGs, including CXCL11, CXCL10, IFIT2, RSAD2 and SAMD9. Gene Ontology analysis of these 32 genes revealed ten enriched biological processes, mainly related to immune response and response to an external stimulus. These data indicate that the endometrial response to the presence of a conceptus varies between uterine horns in the same uterus and may contribute to the higher incidence of pregnancy loss following embryo transfer to the contralateral horn.

Prevalence and determinants of metabolic syndrome in Spanish salaried workers: evidence from 15 614 men and women.

OBJECTIVE: To describe the prevalence of Spanish workers with Metabolic Syndrome (MetS) and those at risk of developing MetS in 2015. METHODS: Cross-sectional study of workers (n = 15 614). We used a modified definition of the NCEP:ATPIII criteria for MetS (we used body mass index (BMI) above 28.8 kg/m2 instead of the waist circumference criterion). We calculated the prevalence of MetS (having at least three components) and of being at risk of MetS (having one or two components). We calculated adjusted odds ratios (aOR) of MetS according to socio-economic and workplace characteristics. RESULTS: The proportions of workers with and at risk of MetS were 7.1 and 31.9%, respectively. The most prevalent criterion was having a BMI > 28.8 kg/m2 (24.1%) in men and cHDL < 40 mg/dl in women (12.9%). There were significant associations between MetS and men (aOR compared to women = 3.73, CI 95%: 3.19; 4.36); age (higher among oldest, aOR = 5.75, CI 95%: 4.37;7.56); and social class (higher among lower social class, aOR = 2.03, CI 95%: 1.65;2.48). CONCLUSION: Reducing any of the five MetS components, while taking into account the differences found by socio-economic and workplace characteristics, should be one priority for reducing MetS prevalence.

Smoking pattern and risk of lung cancer among women participating in cancer screening programmes.

OBJECTIVES: The aim of this study was to describe the smoking prevalence, the smoking pattern, and the risk of lung cancer among women who participated in a cancer screening (breast, cervical and colorectal) in Spain. METHODS: We used data from the Spanish National Health Survey of 2011-12, a cross-sectional study of the adult Spanish population from women in the age of participation in the population cancer screening. We used two definitions of the high risk of lung cancer according to the National Lung Screening Trial (NLST) criteria and the NELSON criteria. RESULTS: Participation in screening was 76.6% in breast cancer, 6.6% in colorectal cancer, and 70.3% in cervical cancer. The percentage of current smokers was 17.1 of women who participated breast cancer, 15.4 of women who participated colorectal cancer, and 26.1 of women who participated cervical cancer. According to NLST criteria, the percentage of current smokers women who had a high risk of lung cancer was 23.1 for breast cancer, 23.5 for colorectal cancer and 4.5 for cervical cancer. These figures were higher with the NELSON criteria. CONCLUSION: At least 250 000 women in Spain have a high risk of lung cancer and are participating in a cancer screening programme. These programmes might be an opportunity for implementing specific interventions aiming to reduce this risk.

The biochemistry surrounding bovine conceptus elongation†.

Conceptus elongation is a fundamental developmental event coinciding with a period of significant pregnancy loss in cattle. The process has yet to be recapitulated in vitro, whereas in vivo it is directly driven by uterine secretions and indirectly influenced by systemic progesterone. To better understand the environment facilitating this critical reproductive phenomenon, we interrogated the biochemical composition of uterine luminal fluid from heifers with high vs physiological circulating progesterone on days 12-14 of the estrous cycle-the window of conceptus elongation-initiation-by high-throughput untargeted ultrahigh-performance liquid chromatography tandem mass spectroscopy. A total of 233 biochemicals were identified, clustering within 8 superpathways [amino acids (33.9%), lipids (32.2%), carbohydrates (8.6%), nucleotides (8.2%), xenobiotics (6.4%), cofactors and vitamins (5.2%), energy substrates (4.7%), and peptides (0.9%)] and spanning 66 metabolic subpathways. Lipids dominated total progesterone (39.1%) and day (57.1%) effects; however, amino acids (48.5%) and nucleotides (14.8%) accounted for most day by progesterone interactions. Corresponding pathways over-represented in response to day and progesterone include (i) methionine, cysteine, s-adenosylmethionine, and taurine (9.3%); (ii) phospholipid (7.4%); and (iii) (hypo)xanthine and inosine purine metabolism (5.6%). Moreover, under physiological conditions, the uterine lumen undergoes a metabolic shift after day 12, and progesterone supplementation increases total uterine luminal biochemical abundance at a linear rate of 0.41-fold day-1-resulting in a difference (P ≤ 0.0001) by day 14. This global metabolic analysis of uterine fluid during the initiation of conceptus elongation offers new insights into the biochemistry of maternal-embryo communication, with implications for improving ruminant fertility.

Biochemical characterization of progesterone-induced alterations in bovine uterine fluid amino acid and carbohydrate composition during the conceptus elongation window†.

Pregnancy establishment in cattle is contingent on conceptus elongation-a fundamental developmental event coinciding with the time during which most pregnancies fail. Elongation in vivo is directly driven by uterine secretions, indirectly influenced by systemic progesterone concentrations, and has yet to be recapitulated in vitro. To better understand the microenvironment evolved to facilitate this phenomenon, the amino acid and carbohydrate composition of uterine fluid was interrogated using high-throughput metabolomics on days 12, 13, and 14 of the estrous cycle from heifers with normal and high circulating progesterone. A total of 99 biochemicals (79 amino acids and 20 carbohydrates) were consistently identified, of which 31 showed a day by progesterone interaction. Fructose and mannitol/sorbitol did not exhibit a day by progesterone interaction, but displayed the greatest individual fluctuations (P ≤ 0.05) with respective fold increases of 18.39 and 28.53 in high vs normal progesterone heifers on day 12, and increases by 10.70-fold and 14.85-fold in the uterine fluid of normal progesterone animals on day 14 vs day 12. Moreover, enrichment analyses revealed that the phenylalanine, glutathione, polyamine, and arginine metabolic pathways were among the most affected by day and progesterone. In conclusion, progesterone had a largely stabilizing effect on amino acid flux, and identified biochemicals of likely importance to conceptus elongation initiation include arginine, fructose, glutamate, and mannitol/sorbitol.

Interferon tau-dependent and independent effects of the bovine conceptus on the endometrial transcriptome†.

This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of interferon tau (IFNT), conceptus origin (in vivo vs. in vitro), and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on day 7 of the estrous cycle. On day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498, and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. A total of 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes [melanophilin (MLPH), prominin-2 (PROM2), myeloid associated differentiation marker (MYADM), vomeronasal 1 receptor 4 like (VN1R4L) and 5-hydroxytryptamine receptor 1A (HTR1A)] were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene [ADP-ribosylation factor like GTPase 4C (ARL4C)] was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment.

Progesterone alters the bovine uterine fluid lipidome during the period of elongation.

Successful bovine pregnancy establishment hinges on conceptus elongation, a key reproductive phenomenon coinciding with the period during which most pregnancies fail. Elongation is yet to be recapitulated in vitro, whereas in vivo it is directly driven by uterine secretions and indirectly influenced by prior circulating progesterone levels. To better understand the microenvironment evolved to facilitate this fundamental developmental event, uterine fluid was recovered on Days 12-14 of the oestrous cycle - the window of conceptus elongation initiation - from cycling heifers supplemented, or not, with progesterone. Subsequent lipidomic profiling of uterine luminal fluid by advanced high-throughput metabolomics revealed the consistent presence of 75 metabolites, of which 47% were intricately linked to membrane biogenesis, and with seven displaying a day by progesterone interaction (P ≤ 0.05). Four metabolic pathways were correspondingly enriched according to day and P4 - i.e. comprised metabolites whose concentrations differed between groups (normal vs high P4) at different times (Days 12 vs 13 vs 14). These were inositol, phospholipid, glycerolipid and primary bile acid metabolism. Moreover, P4 elevated total uterine luminal fluid lipid content on Day 14 (P < 0.0001) relative to all other comparisons. The data combined suggest that maternal lipid supply during the elongation-initiation window is primarily geared towards conceptus membrane biogenesis. In summary, progesterone supplementation alters the lipidomic profile of bovine uterine fluid during the period of conceptus elongation initiation.

Progressive disseminated histoplasmosis in Latin America and the Caribbean in people receiving highly active antiretroviral therapy for HIV infection: A systematic review.

Histoplasmosis is the most clinically significant mycosis in Latin America; still it has been neglected in people with human immunodeficiency virus (HIV). There is limited information about its contribution to morbidity and mortality in this population. We conducted a systematic review of scientific literature to provide an estimation of the frequency and mortality of histoplasmosis among people with HIV receiving highly active antiretroviral therapy (HAART) in Latin America, and factors associated with mortality. We searched articles in PubMed, Scopus, WHO Global health library, and Scielo using different combination of terms including "histoplasmosis" and HAART. We identified 949 articles, removed 662 duplicated; screened 287 abstracts; reviewed full text of 53 articles; and selected 15 articles that provided information on the number of patients studied, included patients receiving ART, and reported any measure of frequency estimate for qualitative synthesis. Studies were conducted in Argentina (n = 4), Brazil (n = 6), Colombia (n = 2), French Guyana and the Bahamas (=2), and Guatemala (n = 1). Heterogeneity of studies characteristics precluded any aggregated estimates. Histoplamosis was frequent in these cohort studies and mortality was high despite the use of HAART. Low CD4 counts, delayed HAART initiation and poor adherence were related to increased incidence, poor prognosis and increased mortality, respectively. Histoplasmosis may be an important contributor to mortality in people with HIV in Latin America. Diagnostic delays represent an important limitation for improving care of patients suspected to have histoplasmosis. Reducing histoplasmosis diagnostic delays and therapy initiation is needed to further decrease mortality.

Relation between tobacco control policies and population at high risk of lung cancer in the European Union.

INTRODUCTION: Lung cancer accounts for nearly 2 million deaths per year worldwide, the majority of cases due to smoking as the main risk factor associated. The aim of this study was to assess the relation between the level of implementation of tobacco control policies and the population at high risk of lung cancer in the European Union (EU). METHODS: The Special Eurobarometer 458 "Attitudes of Europeans towards tobacco and electronic cigarettes", conducted in 2017, and the Tobacco Control Scale (TCS) 2010, 2013, and 2016 were the sources of our data. High risk of lung cancer was defined by the inclusion criteria in the National Lung Screening Trial (NLST) and the Dutch-Belgian Lung Cancer Screening Trial (NELSON), the largest lung cancer screening trials carried out in the US and the EU. We calculated Spearman's rank correlation coefficients (rsp) and fitted multilevel generalized linear mixed models using the quasi-Poisson family to assess the correlation at the national level and analyze the association at the individual level, respectively, between the scores in the TCS (higher scores means better implementation of tobacco control policies) and the proportion of individuals at high risk of lung cancer in member states of the EU. RESULTS: The scores in the TCS 2010 were statistically negatively correlated with the current proportion of ever and former smokers at high risk according to NELSON criteria (-0.41; 95%CI -0.68, -0.04 and -0.49; 95%CI -0.73, -0.13, respectively). We observed statistically significant inverse associations between the scores in the TCS 2010 for the highest quartiles and the proportion of individuals at high risk of lung cancer according to both criteria. Non-statistically significant negative correlations and inverse associations were observed with other TCS. CONCLUSION: There is a lag between the implementation of tobacco control policies and the reduction of the rates of high risk of lung cancer. Member states should reinforce comprehensive tobacco control policies to reduce the population at high risk of lung cancer in the EU.

Comparison of TSNAs concentration in saliva according to type of tobacco smoked.

OBJECTIVE: To compare tobacco-specific nitrosamines (TSNAs) measured in saliva according to different types of tobacco smoked in a sample of smokers of the city of Barcelona (Spain). METHODS: We used data from a cross-sectional study of a sample of the adult smoking population of Barcelona, Spain in 2013-2014 (n = 165). We classified smokers in five groups according to the type of tobacco smoked: a) manufactured cigarettes only, b) roll-your-own (RYO) cigarettes only, c) dual smokers (both manufactured and RYO cigarettes), d) manufactured plus other types of tobacco products different from RYO and e) other types of tobacco products different from manufactured and RYO cigarettes. We calculated the geometric mean (GM) and geometric standard deviation (GSD) of TSNAs concentration in saliva (pg/mL), including N'-nitroaonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) according to the five tobacco groups. We also described all TSNAs concentration in each tobacco group stratified by the number of cigarettes smoked per day. RESULTS: Smokers from the RYO cigarette group had higher TSNAs concentration than smokers from the manufactured cigarette group: 13 pg/mL vs 4.9 pg/mL of NNN, 1.9 pg/mL vs 1.7 pg/mL in NNK and 1.1 pg/mL vs 0.9 pg/mL of NNAL. There were significant differences in NNN concentrations between smokers of RYO vs manufactured cigarettes. The higher the number of cigarettes smoked, the higher the TSNAs concentrations. After adjusted by number of cigarettes smoked, there were not statistically significant differences in TSNAs between RYO and manufactured cigarettes. CONCLUSIONS: Our data shows that RYO cigarette is at least as hazardous as manufactured cigarettes. Regulating RYO tobacco prices could be an effective strategy to control tobacco use.