Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment.

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to other diffusion metrics in the disorder. We conducted a whole-brain voxel-based multicompartment diffusion MRI study on 316 participants (i.e., 158 patients and 158 matched healthy controls) employing four diffusion metrics: the mean diffusivity (MD) and FA estimated from DTI, and the intra-axonal signal fraction (IASF) and microscopic axonal parallel diffusivity (Dpar) derived from the spherical mean technique. Our findings provide novel evidence about widespread abnormalities in other diffusion metrics in BD. An extensive overlap between the FA and IASF results suggests that the lower FA in patients may be caused by a reduced intra-axonal volume fraction or a higher macromolecular content in the intra-axonal water. We also found a diffuse alteration in MD involving white and grey matter tissue and more localised changes in Dpar. A Machine Learning analysis revealed that FA, followed by IASF, were the most helpful metric for the automatic diagnosis of BD patients, reaching an accuracy of 72%. Number of mood episodes, age of onset/duration of illness, psychotic symptoms, and current treatment with lithium, antipsychotics, antidepressants, and antiepileptics were all significantly associated with microstructure abnormalities. Lithium treatment was associated with less microstructure abnormality.

Diagnostic accuracy of anthropometric indices for metabolically healthy obesity in child and adolescent population.

BACKGROUND: A variable percentage of children and adolescents with obesity do not have cardiometabolic comorbidities. A phenotype called metabolically healthy obese (MHO) has emerged to describe this population subgroup. Early identification of this condition may prevent the progression to metabolically unhealthy obesity (MUO). MATERIAL AND METHODS: A cross-sectional descriptive study of 265 children and adolescents from Cordoba (Spain) conducted in 2018. The outcome variables were MHO, established based on three criteria: International Criterion, HOMA-IR, and a combination of the previous two. RESULTS: The prevalence of MHO ranged from 9.4% to 12.8% of the study population, between 41% and 55.7% of the sample with obesity. The highest agreement was reached between the HOMA-IR definitions and the combined criteria. The waist-to-height ratio (WHtR) was the indicator with the highest discriminant capacity for MHO in 2 of the three criteria, with its best cut-off point at 0.47 for both. CONCLUSION: The prevalence of MHO in children and adolescents differed according to the criteria used for diagnosis. The anthropometric variable with the most remarkable discriminating capacity for MHO was WHtR, with the same cut-off point in the three criteria analysed. IMPACT STATEMENT: This research work defines the existence of metabolically healthy obesity through anthropometric indicators in children and adolescents. Definitions that combine cardiometabolic criteria and insulin resistance are used to identify metabolically healthy obesity, as well as the prediction of this phenomenon through anthropometric variables. The present investigation helps to identify metabolically healthy obesity before metabolic abnormalities begin.

Mesothelial-mesenchymal transitions in embryogenesis.

Most animals develop coelomic cavities lined by an epithelial cell layer called the mesothelium. Embryonic mesothelial cells have the ability to transform into mesenchymal cells which populate many developing organs contributing to their connective and vascular tissues, and also to organ-specific cell types. Furthermore, embryonic mesothelium and mesothelial-derived cells produce essential signals for visceral morphogenesis. We review the most relevant literature about the mechanisms regulating the embryonic mesothelial-mesenchymal transition, the developmental fate of the mesothelial-derived cells and other functions of the embryonic mesothelium, such as its contribution to the establishment of left-right visceral asymmetries or its role in limb morphogenesis.

Functional capacity, bone mineral density and neoformation-resorption bone markers in patients under 18 years of age with reduced mobility. / Capacidad funcional, densidad mineral ósea y marcadores de neoformación-reabsorción ósea en pacientes menores de 18 años con movilidad reducida.

INTRODUCTION: Prolonged immobilization associated with several neurological disorders causes se condary osteoporosis with pathological fractures and persistent bone pain. OBJECTIVES: To establish the association between bone mineral density (BMD), neoformation and bone resorption markers and the degree of functional capacity in children under 18 years of age with reduced mobility. Pa tients and Method: Cross-sectional study conducted in Ciudad Real, Spain between January 1, 2016, and December 31, 2017 with patients aged between 6 and 18 years diagnosed with different neuro logical disorders. The following variables were analyzed: age, sex, pubertal stage, functional capacity according to the Functional Mobility Scale (FMS), which assesses the ability to walk from 5, 50 to 500 meters, BMD, 25-hydroxy-vitamin D, alkaline phosphatase and osteocalcin in blood, and N-terminal telopeptide crosslinks in collagen type I (NTX-I) in urine. BMD, alkaline phosphatase, osteocalcin, and NTX-I values are expressed in Z score according to reference values for age and sex. The Pear son and Spearman correlations were used for data analysis. RESULTS: 36 patients (52.7% girls) with an average age of 8.6±4.7 years. Mean FMS value: 5.3 out of 18. Mean BMD: -1.99 ± 1.7 standard deviations (SD), mean alkaline phosphatase: -2.64 ± 1.08, mean osteocalcin: -2.15 ± 1.39, and mean NTX-I: +3 ± 1.72. There was a significant association between BMD and FMS for 5 meters (r = 0.395; p = 0.017) and for total score (r = 0.365; p = 0.029). There were no significant differences according to the stages of pubertal development. CONCLUSIONS: In this population, there was a decrease in BMD and bone neoformation markers, and an increase of bone resorption markers with no association with pubertal development. Patients with a lower degree of mobility present a lower BMD.

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio-venous connections.

Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis.

The Agrobacterium F-Box Protein Effector VirF Destabilizes the Arabidopsis GLABROUS1 Enhancer/Binding Protein-Like Transcription Factor VFP4, a Transcriptional Activator of Defense Response Genes.

Agrobacterium-mediated genetic transformation not only represents a technology of choice to genetically manipulate plants, but it also serves as a model system to study mechanisms employed by invading pathogens to counter the myriad defenses mounted against them by the host cell. Here, we uncover a new layer of plant defenses that is targeted by A. tumefaciens to facilitate infection. We show that the Agrobacterium F-box effector VirF, which is exported into the host cell, recognizes an Arabidopsis transcription factor VFP4 and targets it for proteasomal degradation. We hypothesize that VFP4 resists Agrobacterium infection and that the bacterium utilizes its VirF effector to degrade VFP4 and thereby mitigate the VFP4-based defense. Indeed, loss-of-function mutations in VFP4 resulted in differential expression of numerous biotic stress-response genes, suggesting that one of the functions of VFP4 is to control a spectrum of plant defenses, including those against Agrobacterium tumefaciens. We identified one such gene, ATL31, known to mediate resistance to bacterial pathogens. ATL31 was transcriptionally repressed in VFP4 loss-of-function plants and activated in VFP4 gain-of-function plants. Gain-of-function lines of VFP4 and ATL31 exhibited recalcitrance to Agrobacterium tumorigenicity, suggesting that A. tumefaciens may utilize the host ubiquitin/proteasome system to destabilize transcriptional regulators of the host disease response machinery.

Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA.

DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.

Differential failure to deactivate the default mode network in unipolar and bipolar depression.

OBJECTIVES: Neuroimaging studies have revealed evidence of brain functional abnormalities in bipolar depressive disorder (BDD) and major depressive disorder (MDD). However, few studies to date have compared these two mood disorders directly. METHODS: Matched groups of 26 BDD type I patients, 26 MDD patients and 26 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the n-back working memory task. A whole-brain ANOVA was used to compare the three groups and clusters of significant difference were examined further using region-of-interest (ROI) analysis. RESULTS: The whole-brain ANOVA revealed a single cluster of significant difference in the medial frontal cortex. The BDD and MDD patients both showed failure to deactivate in this area compared to the controls. The BDD patients showed significantly greater failure of deactivation than the MDD patients, which was not accounted for by differences in severity or chronicity of illness between them. CONCLUSIONS: Failure of deactivation, considered to reflect default mode network dysfunction, is present to a greater extent in bipolar than unipolar depression. The study of this network may be useful in the search for brain markers that distinguish the two disorders.

Coelomic epithelium-derived cells in visceral morphogenesis.

Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.

The proepicardium keeps a potential for glomerular marker expression which supports its evolutionary origin from the pronephros.

The proepicardium is the embryonic primordium of the epicardium. This transient structure is essential for cardiac development giving rise to the epicardium and supplying the heart with vascular and cardiac connective tissue progenitors. However, their nature and evolutionary origin are poorly-known. We have suggested elsewhere (Pombal et al. Evol. Dev. 10: 210-216, 2008; Cano et al., J. Dev. Biol. 1: 3-19, 2013) that the proepicardium is an evolutionary derivative of the primordium of an ancient external pronephric glomerulus, devoid of its original excretory function. In this study, we describe for the first time expression of two podocyte markers in the chick proepicardium (glepp1 and synaptopodin) and we have shown how these podocyte markers as well as the intermediate mesoderm marker Pax2 are strongly upregulated when the proepicardium is cultured with nephrogenic inducers. Retinoic acid treatment also induced in the proepicardium expression of Hoxb4, a gene which confers to intermediate mesoderm competence to respond to nephrogenic signals. Thus, a latent nephrogenic potential persists in the proepicardium and also that its original glomerular fate can be partially rescued. The transcription factor Wt1, essential for kidney and epicardial development, plays opposite roles in both tissues, inducing epithelial-mesenchymal transition in the proepicardium and promoting epithelialization in the kidneys (Essafi et al., Dev. Cell 21: 559-574, 2011). Consistently with this antithetical function of Wt1, we have observed an upregulation of podocalyxin in the epicardium of mouse embryos with conditional deletion of the Wt1 gene, while this protein is transcriptionally activated by Wt1 in podocytes.

GATA4 loss in the septum transversum mesenchyme promotes liver fibrosis in mice.

UNLABELLED: The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4 -induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. CONCLUSIONS: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process.

Met signaling in cardiomyocytes is required for normal cardiac function in adult mice.

Hepatocyte growth factor (HGF) and its receptor, Met, are key determinants of distinct developmental processes. Although HGF exerts cardio-protective effects in a number of cardiac pathologies, it remains unknown whether HGF/Met signaling is essential for myocardial development and/or physiological function in adulthood. We therefore investigated the requirement of HGF/Met signaling in cardiomyocyte for embryonic and postnatal heart development and function by conditional inactivation of the Met receptor in cardiomyocytes using the Cre-α-MHC mouse line (referred to as α-MHCMet-KO). Although α-MHCMet-KO mice showed normal heart development and were viable and fertile, by 6 months of age, males developed cardiomyocyte hypertrophy, associated with interstitial fibrosis. A significant upregulation in markers of myocardial damage, such as ß-MHC and ANF, was also observed. By the age of 9 months, α-MHCMet-KO males displayed systolic cardiac dysfunction. Mechanistically, we provide evidence of a severe imbalance in the antioxidant defenses in α-MHCMet-KO hearts involving a reduced expression and activity of catalase and superoxide dismutase, with consequent reactive oxygen species accumulation. Similar anomalies were observed in females, although with a slower kinetics. We also found that Met signaling down-regulation leads to an increase in TGF-ß production and a decrease in p38MAPK activation, which may contribute to phenotypic alterations displayed in α-MHCMet-KO mice. Consistently, we show that HGF acts through p38α to upregulate antioxidant enzymes in cardiomyocytes. Our results highlight that HGF/Met signaling in cardiomyocytes plays a physiological cardio-protective role in adult mice by acting as an endogenous regulator of heart function through oxidative stress control.

Medicolegal assessment of human trafficking victims. Descriptive study of a series of forensic cases in Catalonia (Spain). / Valoración médico-legal de las víctimas de trata de seres humanos. Estudio descriptivo de una serie de casos forenses en Cataluña (España).

BACKGROUND AND OBJECTIVE: Human trafficking or contemporary slavery is the recruitment and transfer of people by force or deception for sexual, labour or other types of exploitation. Although the violence, abuse and deprivation that trafficking entails are a threat to the health of its victims, in Spain the clinical or forensic data available in this regard is scarce. At the Institute of Legal Medicine and Forensic Sciences of Catalonia (IMLCFC), a unit specialized in the forensic assessment of these victims was created. The objective of this work was to describe a series of forensic cases of trafficking victims. MATERIAL AND METHOD: Retrospective study of victims in judicial cases opened for an alleged crime of human trafficking registered in the IMLCFC until 06/30/2023. RESULTS: 57 different victims were registered. The majority were women (71.9%). The average age was 30.5 years (s.d. 10.31). All the victims were foreigners, mostly from Latin America (45.5%). The exploitation was mainly sexual (61.4%). There were some sociodemographic differences and in the conditions and consequences of trafficking between victims of sexual exploitation and the rest. Mental health problems were very common in all victims at the time of the assessment (87.5%). CONCLUSIONS: The consequences of trafficking on health, especially mental health, are notable and the forensic assessment of victims is valuable in judicial proceedings. It is necessary to deepen our knowledge of the phenomenon in our environment.

No association between LH levels and ovarian response in oocyte donors triggered with gonadotropin-releasing hormone agonist: A prospective study.

OBJECTIVE: Are circulating luteinizing hormone (LH) levels predictive of ovarian response in oocyte donors triggered with gonadotropin-releasing hormone (GnRH) agonists? STUDY DESIGN: A prospective cohort study with 224 oocyte donation cycles between 2021 and 2022 at a single center, examined the relationship between circulating luteinizing hormone (LH) levels and ovarian response. Oocyte donors underwent GnRH antagonist downregulation followed by GnRH agonist trigger. LH, estradiol, and progesterone levels were measured on day one of stimulation, trigger-day and 12 h post-trigger. Oocyte retrieval and maturity rates were analyzed using univariate and multivariate analyses, and the correlation between post-trigger LH levels and outcomes was assessed by Pearson's correlation test. A significance level of p < 0.05 was used. RESULTS: Mean age was 26 ± 4.3 years, mean body mass index (BMI, kg/m2) was 22.6 ± 3.2 and mean antral follicle count (AFC) was 21.7 ± 8.2. Post-trigger LH levels averaged 51.3 IU/L (SD 34.8), and oocyte retrieval rate and maturity rates were 112,7% (+/-48,1%) and 77,8% (+/- 17,2%), respectively. No significant differences were found in these outcomes for donors with post-trigger LH values below and above 15 IU/L (Mann Whitney's p > 0.05). However, exploratory analyses revealed that post-trigger LH values < 22 IU/L and basal LH levels < 4 IU/L were associated with significantly lower oocyte retrieval rate (90 % vs 110 %, p = 0.019 and 100 % vs 110 %, p = 0.019, respectively). CONCLUSIONS: This study, a first in exclusively focusing on oocyte donors, did not support the previously reported LH value of 15 IU/L as predictive of suboptimal ovarian response. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05109403.

Sustainable lindane waste remediation: Surfactant-driven residual DNAPL extraction and oxidation in a real landfill (LIFE SURFING).

The LIFE SURFING Project was carried out at the Bailin Landfill in Sabiñánigo, Spain (2020-2022), applying Surfactant Enhanced Aquifer Remediation (SEAR) and In Situ Chemical Oxidation (S-ISCO) in a 60-meter test cell beneath the old landfill, to remediate a contaminated aquifer with dense non-aqueous phase liquid (DNAPL) from nearby lindane production. The project overcame traditional extraction limitations, successfully preventing groundwater pollution from reaching the river. In spring 2022, two SEAR interventions involved the injection of 9.3 m3 (SEAR-1) and 6 m3 (SEAR-2) of aqueous solutions containing 20 g/L of the non-ionic surfactant E-Mulse 3®, with bromide (around 150 mg/L) serving as a conservative tracer. 7.1 and 6.0 m3 were extracted in SEAR-1 and SEAR-2, respectively, recovered 60-70 % of the injected bromide and 30-40 % of the surfactant, confirming surfactant adsorption by the soil. Approximately 130 kg of DNAPL were removed, with over 90 % mobilized and 10 % solubilized. A surfactant-to-DNAPL recovery mass ratio of 2.6 was obtained, a successful value for a fractured aquifer. In September 2022, the S-ISCO phase entailed injecting 22 m3 of a solution containing persulfate (40 g/L), E-Mulse 3® (4 g/L), and NaOH (8.75 g/L) in pulses over 48 h, oxidizing around 20 kg of DNAPL and ensuring low toxicity levels after that. Preceding the SEAR and S-ISCO trials, 2020 and 2021 were dedicated to detailed groundwater flow characterizations, including hydrological and tracer studies. These preliminary investigations allowed the design of a barrier zone between 317 and 557 m from the test cell and the river, situated 900 m away. This zone, integrating alkali dosing, aeration, vapor extraction, and oxidant injection, effectively prevented the escape of fluids to the river. Neither surfactants nor contaminants were detected in river waters post-treatment. The absence of residual phase in test cell wells and reduction of chlorinated compound levels in groundwater were noticed till one year after S-ISCO.

Psychometric properties of the Spanish version of the Health of Nation Outcome Scales for schizophrenia patients.

Accessible Summary What is known on the subject? Functioning is one of the most affected areas in schizophrenia. Social, occupational and personal domains are affected, and these deficits are responsible for a major part of the disability associated with the disorder. There are several instruments to measure functioning, but the HoNOS provides a wide assessment of impairment in 12 areas of functioning. What does the paper add to existing knowledge? The Spanish version of the HoNOS shows good properties in terms of reliability and validity for use in schizophrenia patients. Although some authors divide the scale according to proposed underlying dimensions, in schizophrenia this division may not be appropriate. What are the implications for practice? A reliable and easy-to-use measure of impairment in different areas of functioning is useful for optimizing the treatment and rehabilitation of patients with schizophrenia. ABSTRACT: INTRODUCTION: The HoNOS scale was designed for the assessment of psychosocial impairment in various domains. While it is widely used in psychiatric settings, it has not been validated in Spanish for use in patients with schizophrenia. AIM: To examine the psychometric properties of the Spanish version of the HoNOS scale in a sample of schizophrenia patients. METHOD: A total of 194 individuals aged 18 to 65 with schizophrenia spectrum diagnoses were evaluated using the HoNOS. Illness severity and level of functioning were also assessed. RESULTS: The HoNOS showed moderate internal consistency, good inter-observer reliability and good test-retest reliability. Factor analysis revealed an internal structure consisting of four factors, with item distribution differing from the theoretical dimensions proposed for the original scale. DISCUSSION: The Spanish version of the HoNOS scale is a reliable and valid instrument for assessing psychosocial impairment in individuals diagnosed with schizophrenia spectrum disorders. However, further research is needed to determine its internal structure more accurately. IMPLICATIONS FOR PRACTICE: The HoNOS scale provides researchers and clinicians with a valid measure of impairment in twelve different domains, which can facilitate and guide the treatment of schizophrenia patients.

Wt1-expressing progenitors contribute to multiple tissues in the developing lung.

Lungs develop from paired endodermal outgrowths surrounded by a mesodermal mesenchyme. Part of this mesenchyme arises from epithelial-mesenchymal transition of the mesothelium that lines the pulmonary buds. Previous studies have shown that this mesothelium-derived mesenchyme contributes to the smooth muscle of the pulmonary vessels, but its significance for lung morphogenesis and its developmental fate are still little known. We have studied this issue using the transgenic mouse model mWt1/IRES/GFP-Cre (Wt1cre) crossed with the Rosa26R-EYFP reporter mouse. In the developing lungs, Wt1, the Wilms' tumor suppressor gene, is specifically expressed in the embryonic mesothelium. In the embryos obtained from the crossbreeding, the Wt1-expressing cell lineage produces the yellow fluorescent protein (YFP), allowing for colocalization with differentiation markers. Wt1cre-YFP cells were very abundant from the origin of the lung buds to postnatal stages, contributing significantly to pulmonary endothelial and smooth muscle cells, bronchial musculature, tracheal and bronchial cartilage, as well as CD34⁺ fibroblast-like interstitial cells. Thus Wt1cre-YFP mesenchymal cells show the very same differentiation potential as the splanchnopleural mesenchyme surrounding the lung buds. FSP1⁺ fibroblast-like cells were always YFP⁻; they expressed the common leukocyte antigen CD45 and were apparently recruited from circulating progenitors. We have also found defects in pulmonary development in Wt1-/- embryos, which showed abnormally fused lung lobes, round-shaped and reduced pleural cavities, and diaphragmatic hernia. Our results suggest a novel role for the embryonic mesothelium-derived cells in lung morphogenesis and involve the Wilms' tumor suppressor gene in the development of this organ.

Effectiveness of Multicomponent Interventions and Physical Activity in the Workplace to Reduce Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Overweight and obesity are public health problems that affects the workplace. This paper aims to analyse the effectiveness of workplace health promotion interventions in reducing Body Mass Index (BMI); Methods: Following PRISMA guidelines, a systematic review was conducted using PubMed, MEDLINE, and SCOPUS databases. The inverse variance statistical method was used for the meta-analysis with a random effects analysis model and standardised means. The results have been represented by Forest Plots and Funnel Plots graphs; Results: The multicomponent approach had the best results for reducing BMI (-0.14 [-0.24, -0.03], 95% CI; p = 0.009) compared to performing physical activity only (-0.09 [-0.39, 0.21], 95% CI; p = 0.56). However, both methods resulted in positive changes in reducing BMI in the general analysis (-0.12 [-0.22, -0.02], 95% CI; p = 0.01). The GRADE evaluation showed low certainty due to the high heterogeneity between interventions (I2 = 59% for overall analysis). CONCLUSIONS: The multicomponent approach could be an effective intervention to reduce obesity in the working population. However, workplace health promotion programs must be standardised to conduct quality analyses and highlight their importance to workers' well-being.

Metabolic syndrome and transaminases: systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose, associated with the risk of diabetes, cardiovascular disease and overall mortality. The presence of elevated liver enzymes may precede the development of MetS, with alterations of the liver being observed that are directly related to metabolic problems. The study aims to provide the best evidence on the association between liver enzymes (ALT, AST, GGT) and MetS by determining the effect size of these biomarkers. METHODS: A systematic review and meta-analysis of studies indexed in PubMed and Scopus databases were performed. Study quality was assessed using the STROBE tool. The Grade Pro tool was used to evaluate the evidence, and the quantitative synthesis was performed using RevMan (Cochrane Collaboration). RESULTS: Seventeen articles comparing liver enzyme concentrations between 76,686 with MetS (MetS+) and 201,855 without MetS (MetS-) subjects were included. The concentration of ALT, AST and GGT in the MetS + subjects was significantly higher than in the control group 7.13 IU/L (CI95% 5.73-8.54; p < 0.00001; I2 = 96%), 2.68 IU/L (CI95% 1.82-3.54; p < 0.00001; I2 = 96%) and 11.20 IU/L (CI95% 7.11-15.29; p < 0.00001; I2 = 96%), respectively. CONCLUSIONS: The evaluation of the relationship of liver enzymes in the pathophysiological process of MetS could lead to new insights into early diagnosis.

Association between Metabolic Syndrome and Leukocytes: Systematic Review and Meta-Analysis.

Background: Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by central obesity, hypertension, dyslipidaemia, and dysregulation of blood glucose, which is associated with the risk of diabetes, cardiovascular disease, and overall mortality. White blood cell count is a selective marker of acute infection and inflammation, which could provide information on the metabolic status of subjects. This study aims to provide the best evidence on the association between MetS and white blood cell count by determining the effect size of this biomarker. Methods: A systematic review and meta-analysis of studies indexed in the PubMed and Scopus databases were performed. Methodological quality was assessed using the STROBE tool, overall risk of bias using RevMan (Cochrane Collaboration), and quality of evidence using Grade Pro. Results: We included 14 articles comparing leukocyte concentrations in 21,005 subjects with MetS and 66,339 controls. Subjects with MetS had a higher mean leukocyte count, 0.64 cells ×109/L; CI95% 0.55-0.72; p < 0.00001; I2 = 93%. Conclusions: An in-depth evaluation of the relationship of leukocytes in the pathophysiological process of MetS could lead to new insights into early diagnosis.