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This study was funded by Instituto de Salud Carlos III/Agencia Estatal de Investigación, grant number PI18/00825 Project: ‘Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA’ and Unión Europea (FEDER) ‘Una manera de hacer Europa’; Generalitat Valenciana (GVA/2021/191); D.S.M. holds a postdoctoral grant by the Flemish Scientific Fund (FWO grant 12X9620N). In Sabadell, this study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds, PI15/00118 incl. FEDER funds, CPII18/00018), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010), EU Commission (261357, 308333, 603794 and 634453). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the ‘Centro de Excelencia Severo Ochoa 2019–2023’ Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. In Asturias, this study was funded by ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by FEDER, ‘A way to make Europe’/‘Investing in your future’, Obra Social Cajastur/Fundación Liberbank and Universidad de Oviedo. In Valencia, this study was supported by grants from Instituto de Salud Carlos III [FIS-FEDER: 13/1944, 16/1288, 19/1338; Miguel Servet-FSE: MS15/0025, MSII20/0006 incl. FEDER funds], Generalitat Valenciana [AICO/2020/285] and Gobierno de España through Ministerio de Universidades under the grant CAS21/00008., Petermann-Rocha F, Valera-Gran D, Fernández-Pires P, Martens DS, Júlvez J, Rodríguez-Dehli C, Andiarena A, Lozano M, Fernández-Somoano A, Lertxundi A, Llop S, Guxens M, Nawrot TS, Navarrete-Muñoz EM

Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163]; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction P interaction >0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95]). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. Method: Cross-sectional study with 1279 participants from the INMA cohorts. Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p = 0.026), for cop-per with excess body weight (p < 0.01), low social class (p = 0.03) and being multipara (p < 0.01), for magnesium with being over 35 years old (p = 0.001), high social class (p = 0.044), primiparous status (p = 0.002) and low daily intake of bread (p = 0.009) and legumes (p = 0.020); for zinc with university edu-cation (p = 0.039) and residence in Gipuzkoa (p < 0.01), and for selenium with residence in Valencia (p < 0.01), university education (p = 0.001), vitamin B6 supplementation (p = 0.006), fish intake (> 71 g/day) (p = 0.014) and having been born in Spain (p = 0.001). Further, lower iron levels were associated with being overweight (p = 0.021) or obese (p < 0.001) and vitamin B12 supplementation (p = 0.006). Conclusions: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables. This study is part of the INMA (Infancia y Medio Ambiente) project. It was supported by grants from Instituto de Salud Carlos III (FIS-FEDER: 06/0867, 09/00090, 13/1944, 16/1288, 19/1338; Miguel Servet-FEDER: CP15/0025; Miguel Servet-FSE: MS15/0025) , by the Council of Gipuzkoa (DFG15/009) and by the Health Department of the Basque Government.

Sedentary behaviour (SB) may be related to telomere length (TL) attrition due to a possible pro-inflammatory effect. This study examined the association between parent-reported sedentary behaviour (SB) and leukocyte TL at the age of 4 and telomere tracking from 4 to 8 years. In the Spanish birth cohort Infancia y Medio Ambiente (INMA) project, we analysed data from children who attended follow-up visits at age 4 (n = 669) and 8 (n = 530). Multiple robust regression models were used to explore the associations between mean daily hours of SB (screen time, other sedentary activities, and total SB) at 4 years categorised into tertiles and TL at 4 years and difference in TL rank between age 4 and 8, respectively. At the age of 4, the results showed that children with the highest screen time (1.6–5.0 h/day) had a shorter TL of −3.9% (95% CI: −7.4, −0.4; p = 0.03) compared with children in the lowest tertile (0.0–1.0 h/day). Between 4 and 8 years, a higher screen time (highest tertile group vs. lowest tertile) was associated with a decrease in the LTL rank of −1.9% (95% CI: −3.8, −0.1; p = 0.03) from 4 to 8 years. Children exposed to a higher screen time at 4 years were more prone to have shorter TL at 4 and between 4 and 8 years of age. This study supports the potential negative effect of SB during childhood on cellular longevity. This research was funded by the Instituto de Salud Carlos III/Agencia Estatal de Investigación (PI18/00825: “Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA” and European Regional Development Fund (ERDF): “Una manera de hacer Europa”); the Generalitat Valenciana (GVA/2021/191, CIAICO/2021/132); the Instituto de Salud Carlos III (FIS-PI09/00090, PI04/2018, PI09/02311, PI13/02429, PI16/1288, PI18/00909, PI19/1338 and FIS-PI18/01142 incl. ERFD funds, PS20/0006), the Department of Health of the Basque Government (2013111089); the Instituto de Salud Carlos III (FIS-PI13/02187 and FIS-PI18/01142 incl. ERFD funds), the Department of Health of the Basque Government (2015111065), and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain); Obra Social Cajastur/Fundación Liberbank and Universidad de Oviedo; and Gobierno de España through Ministerio de Universidades under the grants CAS21/00008 and NextGenerationEU. DPB was supported by the Miguel Hernández University (Ayudas Movilidad Internacional 2021, Erasmus+ 2021) during the development of this study. In addition, DM holds a postdoctoral grant by the Flemish Scientific Fund (FWO grant 12X9620N). The funders had no role in the design of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval and submission of the manuscript. The APC was funded by PI18/00825.

(1) Background: Malaria, a vector-borne infectious disease, is caused by parasites of the Plasmodium genus, responsible for increased extreme morbidity and mortality rates. Despite advances in approved vaccines, full protection has not yet been achieved upon vaccination, thus the development of more potent and safe immuno-stimulating agents for malaria prevention is a goal to be urgently accomplished. We have focused our research on a strategy to identify Plasmodium spp. epitopes by naturally acquired human antibodies and rodent malaria infection models immunized with site-directed non-natural antigens. (2) Methods: Some predictive algorithms and bioinformatics tools resembling different biological environments, such as phagosome-lysosome proteolytic degradation, affinity, and the high frequency of malaria-resistant and -sensitive HLA-II alleles were regarded for the proper selection of epitopes and potential testing. Each epitope’s binding profile to both host cells and HLA-II molecules was considered for such initial screening. (3) Results: Once selected, we define each epitope-peptide to be synthesized in terms of size and hydrophobicity, and introduced peptide-bond surrogates and non-natural amino acids in a site-directed fashion, and then they were produced by solid-phase peptide synthesis. Molecules were then tested by their antigenic and immunogenic properties compared to human sera from Colombian malaria-endemic areas. The antigenicity and protective capacity of each epitope-peptide in a rodent infection model were examined. The ability of vaccinated mice after being challenged with P. berghei ANKA and P. yoelii 17XL to control malaria led to the determination of an immune stimulation involving Th1 and Th1/Th2 mechanisms. In silico molecular dynamics and modeling provided some interactions insights, leading to possible explanations for protection due to immunization. (4) Conclusions: We have found evidence for proposing MSP1-modified epitopes to be considered as neutralizing antibody stimulators that are useful as probes for the detection of Plasmodium parasites, as well as for sub-unit components of a site-directed designed malaria vaccine candidate.

BackgroundMercury (Hg) is a toxic heavy metal which humans are most commonly exposed to through food chain contamination, especially via fish consumption. Even low-level exposure can be harmful because of the poor clearance rate, particularly for methylmercury. It is likely that genetic variation modifies exposure through changes in the absorption, metabolism, and/or removal of mercury. Associations have been reported between Hg and variants at multiple genetic loci, but in many cases these results are not yet replicated.MethodsThis study included two populations: pregnant women from the Avon Longitudinal Study of Parents and Children (ALSPAC, n=2,893) and children from the Human Early Life Exposome (HELIX, n=1,042). Genome-wide testing by cohort was performed by fitting linear regressions models on whole blood Hg levels and Haplotype Reference Consortium imputed single-nucleotide polymorphisms (SNPs). SNP heritability was estimated using linkage disequilibrium (LD)-score regression, and the biological functions of the top variants were investigated using resources which aggregate prior literature.ResultsHg SNP heritability was estimated to be 24.0% (95% CI: 16.9% to 46.4%) for pregnant women. The number of genetic variants independently associated with whole blood mercury levels above a suggestive p-value threshold (P < 1×10−5) was 16 for pregnant women and 21 for children. However, none were replicated in both populations, nor did any pass a stronger genome-wide significant threshold (P < 5×10−8). Several suggestive variants had possible biological links to Hg such as rs146099921 in metal transporterSLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channels genes.DiscussionThere was evidence for a considerable proportion of Hg variance being attributed to genome-wide variation in pregnant women. However, results between pregnant women and children were highly discordant which could reflect differences in metabolism and a gene-age interaction with Hg levels. There were a large number of SNPs suggestively associated with Hg levels, which likely include both true associations and false positives. These interim findings will be expanded following collaboration with additional study groups.

BackgroundAcute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) is characterised by heterogeneous levels of disease severity. It is not necessarily apparent whether a patient will develop severe disease or not. This cross-sectional study explores whether acoustic properties of the cough sound of patients with coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV-2, correlate with their disease and pneumonia severity, with the aim of identifying patients with severe disease.MethodsVoluntary cough sounds were recorded using a smartphone in 70 COVID-19 patients within the first 24 h of their hospital arrival, between April 2020 and May 2021. Based on gas exchange abnormalities, patients were classified as mild, moderate or severe. Time- and frequency-based variables were obtained from each cough effort and analysed using a linear mixed-effects modelling approach.ResultsRecords from 62 patients (37% female) were eligible for inclusion in the analysis, with mild, moderate and severe groups consisting of 31, 14 and 17 patients respectively. Five of the parameters examined were found to be significantly different in the cough of patients at different disease levels of severity, with a further two parameters found to be affected differently by the disease severity in men and women.ConclusionsWe suggest that all these differences reflect the progressive pathophysiological alterations occurring in the respiratory system of COVID-19 patients, and potentially would provide an easy and cost-effective way to initially stratify patients, identifying those with more severe disease, and thereby most effectively allocate healthcare resources.

Introduction: Adenomyosis is a heterogeneous condition of difficult diagnosis that stands out in our patients for causing abundant menstrual bleeding, dyspareunia and dysmenorrhoea. However, in chronic pelvic pain units it is important to consider other conditions of similar symptomatologies, such as vascular malformations. These include capillary haemangiomas which, although rare in the reproductive tract, can produce serious symptoms. Case description: We present the case of a 31-year-old woman under observation by the chronic pelvic pain unit for dysmenorrhoea and dyspareunia since menarche. Ultrasound and magnetic resonance findings were compatible with adenomyosis. The patient showed no improvement with hormonal treatment. Upon failure of the medical treatment and taking into account the patient’s lack of gestational desire, a laparoscopic hysterectomy was performed. The pathological report revealed a diffuse capillary haemangioma as the cause of the symptoms. Given the completely curative nature of surgery for this type of condition, the patient was discharged from our unit. Conclusion: The preoperative diagnosis of adenomyosis is still a challenge and units specializing in chronic pelvic pain must consider all possible diagnostic options so as not to overlook rarer conditions such as vascular malformations.

PdM is unready to face the near-future incoming challenges since it is anchored in an obsolete paradigm alien to the incoming cyber-physical reality and unfit for unbelievable data density. In addition to this, PdM is wormed by philosophical hiddenness around time and taxonomies abuse; it is not the sound subdiscipline it appears to be. So, we are doomed to dialogue and get along with AIs if we want to break our human predictiveness ceiling glass and keep PdM improving. In this article, the authors explain not only the turn of the tide but how to flow towards a non-essentialist PdM paradigm.

Establishing proper neighbor relations between a set of spatial units under analysis is essential when carrying out a spatial or spatio-temporal analysis. However, it is usual that researchers choose some of the most typical (and simple) neighborhood structures, such as the first-order contiguity matrix, without exploring other options. In this paper, we compare the performance of different neighborhood matrices in the context of modeling the weekly relative risk of COVID-19 over small areas located in or near Valencia, Spain. Specifically, we construct contiguity-based, distance-based, covariate-based (considering mobility flows and sociodemographic characteristics), and hybrid neighborhood matrices. We evaluate the goodness of fit, the overall predictive quality, the ability to detect high-risk spatio-temporal units, the capability to capture the spatio-temporal autocorrelation in the data, and the goodness of smoothing for a set of spatio-temporal models based on each of the neighborhood matrices. The results show that contiguity-based matrices, some of the distance-based matrices, and those based on sociodemographic characteristics perform better than the matrices based on k-nearest neighbors and those involving mobility flows. In addition, we test the linear combination of some of the constructed neighborhood matrices and the reweighting of these matrices after eliminating weak neighbor relations, without any model improvement.

Introduction and objectives The pocket sized KardiaMobile (KM) is a monitoring device for ECG recording through a smartphone-based application. This system is generally aimed as screening tool to detect alterations in cardiac rhythm but its diagnostic potential for detection of ST changes remains largely unknown. This study sought to assess the diagnostic sensitivity of the KM system for detection of ST changes in patients with ST elevated myocardial infarction (STEMI). Methods Patients admitted with diagnosis of STEMI were consecutively included. Recordings with KM were obtained in leads I, II and anterior precordial. KM recordings were obtained as well from healthy individuals. All recordings were submitted for blinded assessment. Results A total of 112 patients with STEMI and 25 healthy individuals were included. Among those showing ST changes, these consisted mostly in depression (75%). Sensitivity was modest for individual leads (57-58%). The combination of 2-leads, when including the precordial, and the combination of 3-leads markedly increased sensitivity (88-98% and 100% respectively) for both inferior and anterior STEMI. Specificity was very high (96-100%) and the Youden's J statistic was excellent for the 2-leads combinations that included the precordial lead (0.84-0.94) and for the 3-leads combination (0.96). Conclusions The Kardia Mobile system with the combination of 2-leads (I + precordial or II + precordial) or 3-leads shows a very high sensitivity for both anterior and inferior STEMI.

Early exposure to mercury has been related to endocrine disruption. Steroid hormones play a crucial role in neural cell migration, differentiation, etc., as well as protecting against several neurotoxic compounds. We investigate the relation between mercury exposure and children's sexual development, and we evaluate the possible influence of different brain-derived neurotrophic factor (BDNF) polymorphisms on this association. Our study sample comprised 412 9-year-old children participating in the INMA cohort (2004-2015). Mercury concentrations were measured at birth (cord blood) and at 4 and 9 years of age (hair). Sexual development was assessed by levels of sex steroid hormones (estradiol and testosterone) in saliva and the Tanner stages of sex development at 9 years (categorized as 1: prepuberty and1: pubertal onset). Covariates and confounders were collected through questionnaires during pregnancy and childhood. Polymorphisms in the BDNF gene were genotyped in cord blood DNA. Multivariate linear regression analyses were performed between mercury levels and children's sexual development by sex. Effect modification by genetic polymorphisms and fish intake was assessed. We found marginally significant inverse associations between postnatal exposure to mercury (at 9 years) and testosterone levels (β[95%CI] = -0.16[-0.33,0.001], and -0.20[-0.42,0.03], for boys and girls, respectively). Additionally, we found that prenatal mercury was negatively associated with Tanner stage1 in boys. Finally, we found significant genetic interactions for some single nucleotide polymorphisms in the BDNF gene. In conclusion, pre and postnatal exposure to mercury seems to affect children's sexual development and BDNF may play a role in this association, but further research would be needed.

Currently 128 people die daily from opioid-related overdoses in the United States. This burden has instigated a search for viable means to guide postoperative prescription decision-making. The Opioid Risk Tool (ORT) and the Screener and Opioid Assessment for Patient with Pain (SOAPP) are validated risk assessment tools to predict opioid usage in high-risk populations. The purpose of this study was to evaluate the accuracy of these opioid risk assessments and pain intensity scores, including the Patient-Reported Outcomes Measurement Information System (PROMIS), to predict postoperative opioid use and dependence in shoulder surgery.A retrospective review of 81 patients who underwent shoulder surgery and completed 3 preoperative risk and pain assessments within a single hospital system from 2018 to 2020 was performed. Demographic variables and ORT-O, SOAPP-R (the revised version of the SOAPP assessment), and PROMIS 3a scores were recorded from preoperative assessments. Opioid prescriptions were recorded from Electronic-Florida Online Reporting of Controlled Substances Evaluation. Dependence was defined as opioid prescriptions at or greater than 3 months after surgery. Risk assessment scores were compared and tested against postoperative opioid prescriptions using statistical analyses and logistic regression modeling.In the cohort, there were 36 female and 45 male patients with an average age of 64.5 years and body mass index of 28.0. Preoperatively, the average pain score was 6.2, and 7.8% of patients reported prolonged preoperative narcotics use. The average ORT-O score was 3.0, with 35.8% of patients defined as either medium or high risk, and the average PROMIS pain intensity preoperatively was 10.8. Neither the ORT-O nor the PROMIS pain score were good predictors of postoperative opioid dependence (area under curve = 0.39 and 0.43, respectively). The SOAPP-R performed slightly better (area under curve = 0.70) and was the only assessment with significantly different mean scores between patients with postoperative opioid dependence and those without (33.4 and 24.5, respectively,With recent focus on preoperative risk assessments to predict postoperative opioid use and dependence, it is important to understand how well these tools work when applied to orthopedic patients. While the ORT may be helpful in other fields, it does not seem to be a strong predictor of postoperative opioid use or dependence in patients undergoing various types of shoulder surgery. Future studies are needed to explore the utility of the SOAPP-R in a larger sample and identify tools applicable to the orthopedic population to assist surgeons in screening at-risk patients.

A multicountry outbreak of monkeypox has gained global attention. Basic research including structural and immunological investigation on monkeypox virus (MPXV) is central to design effective solutions of treatment with antivirals and appropriate vaccines. We summarize some information about this virus and its re-emergence and the current vaccines that are proposed to limit its spread and present some possible avenues for developing new vaccines.

Tabu search (TS) is a metaheuristic that guides a local heuristic search procedure to explore the solution space beyond local optimality. One of the main components of TS is its use of adaptive memory, which creates a highly flexible search behavior. Memory-based strategies which are the hallmark of TS approaches are founded on a quest for “integrating principles,” by which alternative forms of memory are appropriately combined with effective strategies for exploiting them. The adaptive memory feature of TS allows the implementation of procedures that are capable of searching the solution space economically and effectively. Since local choices are guided by information collected during the search, TS contrasts with memoryless designs that heavily rely on semi-random processes that implement a form of sampling.

This review aims to establish criteria for identifying an adoption process in an archaeological context. We define adoption as raising an individual who does not belong genetically to the family. Adoption appears in different moments of past societies, and when establishing a “family” nucleus burial place we must consider certain social behaviors, such as burials under the houses, collective burials, or laying bodies in specific positions. After observing these signs, we are carrying out a genetic analysis, in order to confirm a biologically related family nucleus. These traces have been traditionally linked to family nuclei because they have been found previously in burials where biological kinship was confirmed. However, there can be cases where, after carrying out the genetic analyses, it is confirmed that certain individuals are not genetically related. In such cases, an adoption case cannot be ruled out. These cases are not easy to identify due to the differences between societies and cultures, so more in-depth studies should be carried out on the type of funeral practice in which these human remains are found to be able to discriminate an adopted individual from one who was not adopted. Therefore, the study of adoption should be carried out based on an in-depth knowledge of the cultural background, before using a powerful tool such as ancient DNA technology.

This chapter is a philosophical essay on how digital ethnography can shed light upon digital hate (especially homicidal hate) and self-harm. The author will do it by attending to the planned (ex)termination of a physical and social individual by herself or by the few ones' havoc against the rest of the people. Likewise, the author will meditate on the reality of lobbies and parties' silent wars and liberticide from different perspectives (post-structuralist, feminist, etc.) to attain a plural view on it while observing the role of digital ethnography in societies ranging from Indonesia to Spain. Therefore, it's an original study that embraces a unique scope of the unwilling ending of human existence and personas from a different and non-politicised angle.

El presente trabajo tuvo como objetivo determinar los costos y beneficios sociales asociados a mejorasambientales, basadas en escenarios económicos hipotéticos en el pozo “El Pital” (Planeta Rica-Córdoba). Seutilizaron los métodos económicos de valoración contingente y costo-efectividad. Para ello, se desarrollótrabajo en campo y se aplicaron encuestas a sus beneficiarios. Los datos obtenidos fueron codificados yregistrados en el software STATA 12.0, definiendo de esta forma los beneficios hipotéticos, a través de laecuación de Hanemann. Luego se presupuestaron los costos asociados a las medidas ambientales planteadas yse estimó la relación costo/beneficio. Dentro de los principales resultados se tiene que, a partir de lascondiciones socioambientales existentes, se plantearon tres medidas hipotéticas que permitirían unaconservación adecuada de El Pital: 1) construcción de un sistema de abastecimiento, 2) impermeabilizaciónde la zona de recarga de los carrocoches y 3) siembra de vegetación nativa. La disposición a pagar por cadalitro de agua para la aplicación de las medidas antes descritas fue de $271 pesos colombianos por cada 20litros de agua comprados. Se concluye que las personas circunscritas al pozo determinan su importancia conrelación a los litros de agua que obtiene de él, el impacto en su trabajo y la historia cultural del mismo. Caberesaltar que aun cuando las medidas sean viables socialmente y en escenarios económicos de carácterhipotéticos, desde la perspectiva sanitaria y ambiental seguiría significando una afectación al recurso y a laspersonas.

The pozzolanic materials have the capacity to modify the performance of Portland cement (PC) mortars. When they are used as supplementary materials, the physical-chemical properties such as compressive-strength and resistance to aggressive environments (chloride, sulphate, acids) are improved. In this article, a study was carried out to evaluate the effects of the addition of two natural pozzolans: volcanic pumice and zeolite. Both used as substitutes for PC in mortars based on cement, considering mechanical strength and the aggressive effect of sulphate ions. Furthermore, the electrochemical behavior of the steel rebar embedded in these mortars was studied during 730 days of exposition to aggressive conditions. The results revealed that the development of the compressive strength of mortars with pozzolans added reached similar values to the reference mortar. It was possible to observe that the addition of the pozzolan suppresses the ettringite formation proportionally to the pozzolan content. The corrosion resistance of the steel improves with the addition of pozzolans after 730 days of exposition at sulphate environment. The results of this study revealed the feasibility to use natural pozzolan as an additive during the preparation of cement up to 25% without significant changes of the physical-chemical properties of the mortars.

The widespread use of cough counting tools has, to date, been limited by a reliance on human input to determine cough frequency. However, over the last two decades advances in digital technology and audio capture have reduced this dependence. As a result, cough frequency is increasingly recognised as a measurable parameter of respiratory disease. Cough frequency is now the gold standard primary endpoint for trials of new treatments for chronic cough, has been investigated as a marker of infectiousness in tuberculosis (TB), and used to demonstrate recovery in exacerbations of chronic obstructive pulmonary disease (COPD). This review discusses the principles of automatic cough detection and summarises key currently and recently used cough counting technology in clinical research. It additionally makes some predictions on future directions in the field based on recent developments. It seems likely that newer approaches to signal processing, the adoption of techniques from automatic speech recognition, and the widespread ownership of mobile devices will help drive forward the development of real-time fully automated ambulatory cough frequency monitoring over the coming years. These changes should allow cough counting systems to transition from their current status as a niche research tool in chronic cough to a much more widely applicable method for assessing, investigating and understanding respiratory disease.

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10-4, p-value = 5.87 × 10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10-7) in GRK1 and cg02212000 (β = -0.001, p-value = 8.13 × 10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations. INMA: Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03–1615, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338; Miguel Servet FEDER 15/0025 and 20/0006; FIS-FSE: 17/00260), Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat Valenciana BEST/2020/059, Fundacio ́ La Marato ́ de TV3 (090,430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn). Korean exposome study: This study was supported by the Korean Environment Industry & Technology Institute (KEITI) through “the Environmental Health Action Program”, funded by Korea Ministry of Environment (2017001360005). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and Norwegian Research Council/BIOBANK (grant no 221097). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club, all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA/Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND). Project Viva: The Project Viva cohort is funded by NIH grants R01HL111108, R01NR013945, and R37 HD034568. RHEA: The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014; ‘Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The work was also supported by MICINN (MTM2015-68140-R), Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII, the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)).

Electronic cigarettes (e-cigs) and vaping are a popular form of substance abuse among adolescents. Studies have shown that adolescents have a poor understanding of e-cigs but little is known about parental understanding. The primary objective was to assess if a discrepancy in perception and knowledge regarding the content and safety profile of e-cigs between adolescents and their parents exists.Single-site prospective questionnaire analysis of adolescents (12-21 years) and their parents between November 2018 and March 2019 was performed. Each participant pair received an anonymous, confidential, electronic questionnaire. Data were collected via Research Electronic Data Capture. χ2 and independent t tests were used for comparative analysis.A total of 300 adolescent/parent pairs were included for analysis. The mean age of adolescents was 15.1 years (SD, 2.1), and that of parents was 43.9 years (SD, 8.7). Overall knowledge of e-cigs was inadequate in both adolescents and parents: 93.7% and 88.3%, respectively (P0.0001). Less adolescents (49.0%) compared with parents (71.0%) perceived any health risks to smoking e-cigs (P0.0001). Among adolescents, 17% admitted to smoking e-cigs compared with 5.4% smoking conventional tobacco cigarettes (P0.0001), and they reported using e-cigs (17.0%) more often than any other substance except alcohol (27.3%). Only 49.7% of adolescents reported receiving formal education at school regarding e-cigs. Parents reported discussing e-cigs risks/benefits with adolescents less often than other topics (71.3% vs 79.0% to 84.3%; P0.0007).This analysis suggests that perception and knowledge regarding the content and safety profile of e-cigs are poor among both adolescents and parents. These findings support the need for tighter federal regulation and an increase in public health awareness programs.

This study was funded by Grants from EU (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1); Spain: ISCIII (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/00090, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02187, PI14/00891, PI14/01687, PI16/1288, PI17/00663, PI18/01142 and PI19/1338; Miguel Servet FEDER MS15/00025, MS20/0006, CPII16/00051, and FIS-FSE: 17/00260); CIBERESP; Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), AICO/2020/285, and Alicia Koplowitz Foundation 2017; Generalitat de Catalunya-CIRIT 1999SGR 00241; Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065); Provincial Government of Gipuzkoa (DFG06/002, DFG08/001 and DFG15/221). We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the "Centro de Excelencia Severo Ochoa 2019-2023" Programme (CEX2018000806-S), and from the Generalitat de Catalunya through the CERCA Programme, as well as the municipalities in the study area., Background: Humans are regularly exposed to metals and metalloids present in air, water, food, soil and domestic materials. Most of them can cross the placental barrier and cause adverse impacts on the developing foetus. Objectives: To describe the prenatal concentrations of metals and metalloids and to study the associated sociodemographic, environmental and dietary factors in pregnant Spanish women. Methods: Subjects were 1346 pregnant women of the INMA Project, for whom the following metals arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), thallium (Tl) and zinc (Zn) were determined in urine, at both the first and the third trimesters of gestation. Sociodemographic, dietary and environmental information was collected through questionnaires during pregnancy. Multiple linear mixed models were built in order to study the association between each metal and metalloid concentrations and the sociodemographic, environmental and dietary factors. Results: The most detected compounds were As, Co, Mo, Sb, Se and Zn at both trimesters. Zn was the element found in the highest concentrations at both trimesters and Tl was detected in the lowest concentrations. We observed significant associations between As, Cd, Cu, Sb, Tl and Zn concentrations and working situation, social class and age. Seafood, meat, fruits, nuts, vegetables and alcohol intake affected the levels of all the metals but Cd and Cu. Proximity to industrial areas, fields and air pollution were related to all metals except Cd, Sb and Se. Conclusions: This is the first large prospective longitudinal study on the exposure to metals and metalloids during pregnancy and associated factors to include several cohorts in Spain. The present study shows that some modifiable lifestyles, food intakes and environmental factors could be associated with prenatal exposure to metal (loid)s, which may be considered in further studies to assess their relationship with neonatal health outcomes., European Commission 282957 HEALTH.2010.2.4.5-1, Spain: ISCIII Red INMA G03/176 CB06/02/0041 CIBERESP, Generalitat Valenciana: FISABIO UGP 15-230 UGP-15-244 UGP-15-249 AICO/2020/285, Alicia Koplowitz Foundation, Generalitat de Catalunya, General Electric CIRIT 1999SGR 00241, Department of Health of the Basque Government 2005111093 2009111069 2013111089 2015111065, Provincial Government of Gipuzkoa DFG06/002 DFG08/001 DFG15/221, Spanish Ministry of Science, Innovation and Universities CEX2018000806-S, General Electric, Spain (FIS-FEDER) PI03/1615 PI04/1509 PI04/1112 PI04/1931 PI05/1079 PI05/1052 PI06/0867 PI06/1213 PI07/0314 PI09/00090 PI09/02647 PI11/01007 PI11/02591 PI11/02038 PI13/1944 PI13/2032 PI13/02187, Spain (Miguel Servet FEDER) MS15/00025 MS20/0006 CPII16/00051, Spain (FIS-FSE) 17/00260, the Spain (FIS-FEDER) PI14/00891 PI14/01687 PI16/1288 PI17/00663 PI18/01142 PI19/1338

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMG para and sMMG para , and sEMG lic and sMMG lic , respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMG para , sMMG para , sEMG lic , sMMG lic , mouth pressure (P mo ), and volume (V i ) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMG para%max , fSEsMMG para%max , fSEsEMG lic%max , and fSEsMMG lic%max ). fSEsMMG para%max , fSEsEMG para%max , and fSEsEMG lic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. P mo -derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, V i -derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of P mo and V i to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.

INTRODUCTION AND OBJECTIVES: Equal opportunities to access technical advances with recognized clinical value should be a priority of the publicly-funded health system. We analyzed variability among all the Spanish autonomous communities in the use of cardiovascular techniques with an established indication and its relationship with economic indicators, burden of disease, and hospital mortality. METHODS: The activity registries of various Associations of the Spanish Society of Cardiology from 2011 to 2019 were analyzed for coronary angiography, overall percutaneous coronary intervention (PCI), primary PCI, implantable cardioverter-defibrillators (ICD), cardiac resynchronization therapy, and transcatheter aortic valve replacement (TAVR). Economic indices (gross domestic product and per capita health care expenditure) were obtained from public sources and data on attendance rates and mortality from the Resources and Quality in Cardiology (RECALCAR) reports of the Spanish Society of Cardiology. We analyzed the coefficient of variation for activity and the correlation of activity with regional economic indices, attendance rates, and risk-adjusted rates of in-hospital mortality. RESULTS: We identified wide variability in the use of technologies, especially for primary PCI (18%), ICD (22%), cardiac resynchronization therapy (36%), and TAVR (42%). A certain correlation with attendance rates was seen only for overall PCI and ICD. In general, no significant correlation was found between the use of the techniques and the economic indices of wealth and expenditure. The correlation with in-hospital mortality showed no significant results, although this was the analysis with the greatest limitations because the impact of these techniques on survival is exerted more in the mid- and long-term. CONCLUSIONS: The results of this study, despite its inherent limitations, show marked variability between autonomous communities in the use of cardiovascular technologies, which is not explained by economic differences or by hospital attendance rates due to the corresponding diseases.

Background: Uterine adenomyosis is an increasingly frequent disorder. Our study aimed to demonstrate the presence of obstetric complications in the population affected by this condition to demonstrate the need for follow-up in high-risk obstetric units. Material and Methods: The data for the study were obtained from TriNetX, LLC, between 2010 and 2020. The outcomes analyzed were intrauterine growth restriction (IUGR), preterm delivery, cesarean delivery, hypertension, abruption placentae, and spontaneous abortion. Seven thousand six hundred and eight patients were included in the cohort of pregnant patients with adenomyosis, and 566,153 women in the cohort of pregnant patients without any history of endometriosis. Results: Upon calculating the total risk of presenting any of these problems during pregnancy, we obtained an OR = 1.521, implying that a pregnancy with adenomyosis was 52.1% more likely to present some complication. We found: IUGR OR = 1.257 (95% CI: 1.064–1.485) (p = 0.007); preterm delivery OR = 1.422 (95% CI: 1.264–1.600) (p = 0.0001); cesarean delivery OR = 1.099 (95% CI: 1.002–1.205) (p = 0.046); hypertensive disorders OR = 1.177 (95% CI: 1.076–1.288) (p = 0.0001); abruption placentae OR = 1.197 (95% CI: 1.008–1.422) (p = 0.040), and spontaneous abortion OR = 1.529 (95% CI: 1.360–1.718) (p = 0.0001). Conclusion: We conclude that the review carried out and the data we obtained on increased risk provide sufficient evidence to recommend that patients with adenomyosis should be managed in obstetric high-risk units.

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are typical contaminants of food and feed, which have serious implications for human and animal health, even at low concentrations. Therefore, a transcriptomic study was carried out to analyze gene expression changes triggered by low doses of AFB1 and OTA (100 nM; 7 days), individually and combined, in human lymphoblastic T cells. RNA-sequencing analysis showed that AFB1-exposure resulted in 99 differential gene expressions (DEGs), while 77 DEGs were obtained in OTA-exposure and 3236 DEGs in the combined one. Overall, 16% of human genome expression was altered. Gene ontology analysis revealed, for all studied conditions, biological processes and molecular functions typically associated with the immune system. PathVisio analysis pointed to ataxia telangiectasia mutated signaling as the most significantly altered pathway in AFB1-exposure, glycolysis in OTA-exposure, and ferroptosis in the mixed condition (Z-score > 1.96; adjusted p-value ≤ 0.05). Thus, the results demonstrated the potential DNA damage caused by AFB1, the possible metabolic reprogramming promoted by OTA, and the plausible cell death with oxidative stress prompted by the mixed exposure. They may be considered viable mechanisms of action to promote immune toxicity in vitro.