Nutritional, pharmacological, and environmental programming of NAFLD in early life.

Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.

Awe, curiosity, and multicultural experience.

INTRODUCTION: Despite broad consensus about multicultural experience's benefits, there is a lack of research on the antecedents to multicultural experiences. Research has indicated that awe shifts attention away from the self toward larger entities, which could include elements of other cultures. METHODS: Four studies (N = 2915) tested whether trait, daily, and induced awe promoted multicultural experience. RESULTS: Studies 1-2 (adolescents, young, middle, and older adults) showed that trait awe predicted greater multicultural identity and experience independent of other positive emotions and openness. Study 3 (students & adults in U.S. & Malaysia) demonstrated that daily awe predicted more daily multicultural experience independent of yesterday's multicultural experience. These results were explained by trait and daily curiosity. Study 4 (adults) found that induction of awe increased state multicultural identity and experience via state curious emotions and then state curious personality. CONCLUSION: We found that experiencing more awe can be a tool for enhancing the multicultural experience. The discussion focuses on the implications for future research on awe and multicultural experiences.

Non-invasive diagnosis of non-alcoholic fatty liver disease using an algorithm combining clinical indexes and ultrasonographic measures.

INTRODUCTION AND OBJECTIVE: Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic liver disease related to insulin resistance, which requires invasive methods for diagnosis. The aim of this study was to analyze whether the use of an algorithm involving both clinical indices and hepatic ultrasound measurements improves the accuracy for the non-invasive diagnosis of NAFLD. PATIENTS AND METHODS: Cross-sectional study with patients undergoing elective cholecystectomy. We collected anthropometric, metabolic, liver biopsy, and liver ultrasonography data. We calculated unpaired t-test and Pearson's coefficient, and areas under the receiver-operating characteristic curves (AUROC) for the Fatty Liver Index (FLI), Lipid Accumulation Product (LAP) indexes, right liver index diameter, and for predictive models constructed with discriminant analysis. RESULTS: One hundred patients in groups with and without NAFLD. FLI, LAP, right and caudate liver lobe diameters, and congestion index were higher in NAFLD group (p = 0.011, p = 0.011, p = 0.001, p = 0.027, p = 0.009). The right liver lobe diameter had the highest AUROC. Predictive models that combined sensitivity and specificity for the clinical indexes and liver ultrasound had an AUROC over 0.7. CONCLUSION: The ultrasonography measure of right liver lobe diameter by itself can reliably identify patients with NAFLD with a good sensitivity and specificity, however, this can be improved by adding the LAP mathematical index in our population.

Association of placental nutrient sensing pathways with birth weight.

Birth weight (BW) is an important indicator for newborn health. Both high and low BW is associated with increased risks for adult metabolic diseases. AMPK (AMP-activated protein kinase), mTOR (mechanistic target of rapamycin), and insulin/IGF1 (insulin-like growth factor 1) pathways may function as placental sensors of maternal hormonal and nutritional status. However, the physiological role of these pathways in placenta has not been completely elucidated. To evaluate expression and activation of AMPK, mTOR, and insulin/IGF1 pathways and its association with placental weight (PW), BW, and maternal hormonal and metabolic status, we performed a cross-sectional study in placentas from non-obese mothers with SGA (n = 17), AGA (n = 19) and LGA (n = 10) newborns. We analyzed placental expression of total and phosphorylated key proteins from the AMPK, mTOR and insulin/IGF1 pathways. Maternal and cord blood hormones were determined by ELISA. AMPK and LKB1 activation correlated negatively with PW and BW, cord leptin, and pregestational BMI. Placental SIRT1 inversely correlated with BW, cord leptin, neonatal HOMA-IR, and maternal IGF1. PGC1α correlated negatively with PW and BW. Phosphorylated mTOR positively correlated with maternal glucose, PW and BW. IGF1R was lower in SGA. No changes in p-IGF1R, INSRb, total AKT or p-AKT were found, and pPDK1 was lower in SGA and LGA. These results suggest that placental AMPK, insulin/IGF1, and mTOR pathways may influence fetal growth, perhaps regulating placental physiology, even in metabolically healthy pregnancies. Our study highlights these nutrient sensing pathways as potential molecular mechanisms modulating placental adaptations and, thus, long-term metabolic health.

Early-life programming of adipose tissue.

Worldwide obesity is increasing at an alarming rate in children and adolescents, with the consequent emergence of co-morbidities. Moreover, the maternal environment during pregnancy plays an important role in obesity, contributing to transgenerational transmission of the same and metabolic dysfunction. White adipose tissue represents a prime target of metabolic programming induced by maternal milieu. In this article, we review adipose tissue physiology and development, as well as maternal influences during the perinatal period that may lead to obesity in early postnatal life and adulthood. First, we describe the adipose tissue cell composition, distribution and hormonal action, together with the evidence of hormonal factors participating in fetal/postnatal programming. Subsequently, we describe the critical periods of adipose tissue development and the relationship of gestational and early postnatal life with healthy fetal adipose tissue expansion. Furthermore, we discuss the evidence showing that adipose tissue is an important target for nutritional, hormonal and epigenetic signals to modulate fetal growth. Finally, we describe nutritional, hormonal, epigenetic and microbiome changes observed in maternal obesity, and whether their disruption alters fetal growth and adiposity. The presented evidence supports the developmental origins of health and disease concept, which proposes that the homeostatic system is affected during gestational and postnatal development, impeding the ability to regulate body weight after birth, thereby resulting in adult obesity. Consequently, we anticipate that promoting a healthy early-life programming of adipose tissue and increasing the knowledge of the mechanisms by which maternal factors affect the health of future generations may offer novel strategies for explaining and addressing worldwide health problems such as obesity.

Are awe-prone people more curious? The relationship between dispositional awe, curiosity, and academic outcomes.

OBJECTIVE: Guided by a functional account of awe, we aimed to test the hypothesis that people who often feel awe are also more curious (Studies 1 and 2), and that this relationship in turn relates to academic outcomes (Study 3). METHOD: In Study 1 (n = 1,005), we used a self-report approach to test the relationship between dispositional awe and curiosity. In Study 2 (n = 100), we used a peer-report approach to test if participants' dispositional awe related to how curious they were rated by their friends. In Study 3, in a sample of 447 high school adolescents we tested if dispositional awe related to academic outcomes via curiosity. RESULTS: We found that dispositional awe was positively related to people's self-rated curiosity (Study 1) and how curious they were rated by their friends (Study 2). In Study 3, we found that dispositional awe was related to academic outcomes via curiosity. CONCLUSIONS: We conclude that among the seven positive emotion dispositions tested, awe was related to unique variance in curiosity, and this link in turn predicted academic outcomes. This work further characterizes awe as an epistemic emotion and suggests that activities that inspire awe may improve academic outcomes.

Leptin and its Receptors in Human Placenta of Small, Adequate, and Large for Gestational Age Newborns.

Alterations in birth weight impact postnatal outcome and adult metabolic health. Therefore, fetal growth regulation is crucial for preventing chronic metabolic diseases. Leptin has been suggested to play an important role in placental and fetal growth, albeit its specific mechanisms of action have not been elucidated. The aim of this study was to analyze leptin concentrations in placenta, cord blood, and maternal blood of SGA, AGA, and LGA (small, adequate and large for gestational age, respectively) newborns, as well as placental leptin receptor (LEPRa and LEPRb) protein expression. We performed a cross-sectional comparative study in 3 groups of healthy mothers and their term newborns at delivery (SGA, AGA, and LGA, n=20 per group). Placental, maternal blood, and cord blood leptin content were measured by ELISA. Placental LEPRa and LEPRb protein expression were determined by Western Blot. Maternal leptin concentrations correlated positively with maternal weight before and at the end of gestation, without differences between groups. Cord leptin is higher in LGA and lower in SGA, whereas placental leptin is higher in SGA. Placental leptin was inversely correlated with placental weight, independently from maternal weight and gestational age. Both LEPRa and LEPRb expression are lower in SGA, while LEPRa positively correlated with placental weight and birthweight. The current findings indicate that placental leptin and its receptors are differentially expressed in SGA, AGA, and LGA newborns. We suggest that placental leptin and LEPR protein expression may influence placental growth and thus, birth weight.

Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome.

BACKGROUND: Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS. METHODS: Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 µg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 µg) in HLA-DR4 transgenic mice. RESULTS: Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS. CONCLUSIONS: Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than IL-2, IL-6 and TNF are likely to play critical mechanistic roles in the pathogenesis of experimental TSS.

Detection and molecular characterization of porcine circovirus type 2 from piglets with porcine circovirus associated diseases in Colombia.

BACKGROUND: The porcine circovirus-associated disease (PCVAD) has been known since 1991 in Canada, but the first outbreak of PCVAD in Colombia was reported in 2007. In order to understand the molecular epidemiology of the disease and to establish the origin of the virus in the country, the study presented here intended to evaluate the presence of PCV2-associated systemic infection in piglets from different geographical regions over a period of 9-years (2002-2010). The analysis included samples collected before, during and after outbreaks of PCVAD in pigs from Colombia. The PCV2 ORF2 from the positive samples was sequenced and used to determine the genotypes of the strains and to study the dynamic of these genotypes throughout the time. RESULTS: PCV2 DNA was detected in cases related to PCV2-associated systemic infection as well as in healthy pigs with a presumable persistent infection. The analysis of the ORF2 nucleotide full length sequence of twenty-three strains allowed to divide them into two groups: PCV2a and PCV2b. At the amino acid level the main variations in the sequence of the capsid protein were found in regions located within the immunoreactive areas. CONCLUSIONS: The results of this study demonstrated for the first time, that the two subgroups: PCV2a and PCV2b have been circulating in swine from Colombia. In addition, the study showed that genotype PCV2b is present in Colombian pigs suffering from both clinical and presumable persistent infection and that the PCV2b genotype was present in the Colombian pig population even before recognition of the disease in the country and it became predominant through time.

Deep learning reveals what facial expressions mean to people in different cultures.

Cross-cultural studies of the meaning of facial expressions have largely focused on judgments of small sets of stereotypical images by small numbers of people. Here, we used large-scale data collection and machine learning to map what facial expressions convey in six countries. Using a mimicry paradigm, 5,833 participants formed facial expressions found in 4,659 naturalistic images, resulting in 423,193 participant-generated facial expressions. In their own language, participants also rated each expression in terms of 48 emotions and mental states. A deep neural network tasked with predicting the culture-specific meanings people attributed to facial movements while ignoring physical appearance and context discovered 28 distinct dimensions of facial expression, with 21 dimensions showing strong evidence of universality and the remainder showing varying degrees of cultural specificity. These results capture the underlying dimensions of the meanings of facial expressions within and across cultures in unprecedented detail.

Awe as a Pathway to Mental and Physical Health.

How do experiences in nature or in spiritual contemplation or in being moved by music or with psychedelics promote mental and physical health? Our proposal in this article is awe. To make this argument, we first review recent advances in the scientific study of awe, an emotion often considered ineffable and beyond measurement. Awe engages five processes-shifts in neurophysiology, a diminished focus on the self, increased prosocial relationality, greater social integration, and a heightened sense of meaning-that benefit well-being. We then apply this model to illuminate how experiences of awe that arise in nature, spirituality, music, collective movement, and psychedelics strengthen the mind and body.

The influences of daily experiences of awe on stress, somatic health, and well-being: a longitudinal study during COVID-19.

In the present work, we used daily diary methodology to investigate the influence of awe on stress, somatic health (e.g., pain symptoms), and well-being during the COVID-19 pandemic in 2020. We recruited a sample of community adults (N = 269) and a sample of healthcare professionals (N = 145) in the United States. Across both samples, we found that awe and well-being increased, and stress and somatic health symptoms decreased over the 22-day diary period. In daily level analyses, we found that the more daily awe people experienced, the less stress, less somatic health symptoms, and greater well-being they felt. Daily experiences of awe can benefit individuals during times of acute and chronic stress-such as the COVID-19 pandemic.

Deep learning reveals what vocal bursts express in different cultures.

Human social life is rich with sighs, chuckles, shrieks and other emotional vocalizations, called 'vocal bursts'. Nevertheless, the meaning of vocal bursts across cultures is only beginning to be understood. Here, we combined large-scale experimental data collection with deep learning to reveal the shared and culture-specific meanings of vocal bursts. A total of n = 4,031 participants in China, India, South Africa, the USA and Venezuela mimicked vocal bursts drawn from 2,756 seed recordings. Participants also judged the emotional meaning of each vocal burst. A deep neural network tasked with predicting the culture-specific meanings people attributed to vocal bursts while disregarding context and speaker identity discovered 24 acoustic dimensions, or kinds, of vocal expression with distinct emotion-related meanings. The meanings attributed to these complex vocal modulations were 79% preserved across the five countries and three languages. These results reveal the underlying dimensions of human emotional vocalization in remarkable detail.

Polymorphisms -374 T/A and -429 T/C of the Receptor for Advanced Glycation End-Products (RAGE) and Serum Levels of RAGE (sRAGE) Are Not Associated with Metabolic Syndrome.

RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant, proposed as an inhibitor of RAGE activity. -374 T/A and -429 T/C polymorphisms of the advanced glycation end products receptor AGER gene are associated with the development of some diseases, such as type of cancer, cardiovascular disease, and micro and macrovascular disease in diabetes among others but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy men without MS, and 80 men with MS according to the harmonized criteria. -374 T/A and -429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between Non-MS and MS groups (-374 T/A p = 0.48, p = 0.57 and -429 T/C p = 0.36, p = 0.59). Significant differences were found in fasting glucose levels and diastolic blood pressure among the genotypes of the -374 T/A polymorphism in the Non-MS group (p < 0.01 and p = 0.008). Glucose levels were different between -429 T/C genotypes in the MS group (p = 0.02). sRAGE levels were similar in both groups, but in the Non-MS group showed a significant difference between individuals with only 1 or 2 components of the metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for -374 T/A; recessive model p = 0.48, dominant model p = 0.42 for -429 T/C). -374 T/A and -429 T/C polymorphisms are not associated with MS in Mexican population and have no influence on serum sRAGE levels.

Correlation of the pediatric metabolic index with NAFLD or MAFLD diagnosis, and serum adipokine levels in children.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic fat deposition in the liver. However, a recent classification of this condition, which also integrates the presence of coexisting metabolic disorders, termed Metabolic dysfunction Associated Fatty Liver Disease (MAFLD), has been proposed. NAFLD is increasingly common in early childhood, partly due to the increase in metabolic disease in this age. Thus, studying hepatic steatosis in the metabolic context has become important in this population as well. However, NAFLD, and thus MAFLD, diagnosis in children is challenging by the lack of non-invasive diagnostic tools comparable to the gold standard of hepatic biopsy. Recent studies have reported that the Pediatric Metabolic Index (PMI) could be a marker of insulin resistance and abnormal liver enzymes, but its association with NAFLD, MAFLD, or altered adipokines in these conditions has not been reported. The aim of this study is to evaluate the correlation between PMI with the diagnosis of NAFLD or MAFLD, together with serum levels of leptin and adiponectin, in school-age children. METHODS: A cross sectional study was carried out in two hundred and twenty-three children without medical history of hypothyroidism, genetic, or chronic diseases. Anthropometry, liver ultrasound, and serum levels of lipids, leptin, and adiponectin were evaluated. The children were classified as having NAFLD or non-NAFLD, and a subgroup of MAFLD in the NAFLD group was analyzed. The PMI was calculated by the established formulas for age and gender. RESULTS: PMI correlated positively with the presence and severity of NAFLD (r = 0.62, p<0.001 and r = 0.79, p<0.001 respectively) and with the presence of MAFLD (r = 0.62; p<0.001). Also, this index correlated positively with serum leptin levels (r = 0.66; p<0.001) and negatively with serum adiponectin levels (r= -0.65; p<0.001). PMI showed to be a good predictor for diagnosing NAFLD in school-age children when performing a ROC curve analysis (AUROC=0.986, p< 0.0001). CONCLUSION: PMI could be a useful tool for the early diagnosis of NAFLD or MAFLD in children. However, future studies are necessary to establish validated cut-off points for each population.

Sequence-Based Antigenic Analyses of H1 Swine Influenza A Viruses from Colombia (2008-2021) Reveals Temporal and Geographical Antigenic Variations.

Swine influenza is a respiratory disease that affects the pork industry and is a public health threat. It is caused by type A influenza virus (FLUAV), which continuously undergoes genetic and antigenic variations. A large amount of information regarding FLUAV in pigs is available worldwide, but it is limited in Latin America. The HA sequences of H1 subtype FLUAV-positive samples obtained from pigs in Colombia between 2008-2021 were analyzed using sequence-based antigenic cartography and N-Glycosylation analyses. Of the 12 predicted global antigenic groups, Colombia contained five: four corresponding to pandemic strains and one to the classical swine H1N1 clade. Circulation of these clusters was observed in some regions during specific years. Ca2 was the immunodominant epitope among Colombian viruses. The counts of N-Glycosylation motifs were associated with the antigenic cluster ranging from three to five. The results show for the first time the existence of antigenic diversity of FLUAV in Colombia and highlight the impact of spatial and temporal factors on this diversity. This study provides information about FLUAV variability in pigs under natural conditions in the absence of vaccination and emphasizes the need for surveillance of its phylogenetic and antigenic characteristics.

Molecular and Pathological Characterization of Classical Swine Fever Virus Genotype 2 Strains Responsible for the 2013-2018 Outbreak in Colombia.

Classical swine fever (CSF) is a highly contagious transboundary viral disease of domestic and wild pigs. Despite mass vaccination and continuous eradication programs, CSF remains endemic in Asia, some countries in Europe, the Caribbean and South America. Since June 2013, Northern Colombia has reported 137 CSF outbreaks, mostly in backyard production systems with low vaccination coverage. The purpose of this study was to characterize the virus responsible for the outbreak. Phylogenetic analysis based on the full-length E2 sequence shows that the virus is closely related to CSF virus (CSFV) genotype 2.6 strains circulating in Southeast Asia. The pathotyping experiment suggests that the virus responsible is a moderately virulent strain. The 190 nucleotide stretch of the E2 hypervariable region of these isolates also shows high similarity to the CSFV isolates from Colombia in 2005 and 2006, suggesting a common origin for the CSF outbreaks caused by genotype 2.6 strains. The emergence of genotype 2.6 in Colombia suggests a potential transboundary spread of CSFV from Asia to the Americas, complicating the ongoing CSF eradication efforts in the Americas, and emphasizes the need for continuous surveillance in the region.

Desacylghrelin modulates GHS-R1 receptor expression and cell differentiation in placental BeWo cells.

BACKGROUND: and purpose: Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (GHS-R1). Ghrelin, and GHS-R1, may have a role in placental growth and function, and its unacylated form desacylghrelin (DAG) could be involved in fetal growth. Nevertheless, the effects of DAG on placental function, and the receptor involved in its actions, remain to be determined. We aimed to investigate the effect of DAG in placental BeWo cells viability, proliferation, differentiation, and GSH-R1 expression. METHODS: BeWo cells, a human trophoblast cell line, was cultured with 3 nM DAG during 12, 24, 48, and 72 h. Cell viability, proliferation, differentiation (assessed by human Chorionic Gonadotropin quantification), and GSH-R1 expression were analyzed. To evaluate the mechanism of DAG effect on GSH-R1, 30 nM receptor antagonist ([D-Lys3]-GHRP-6) was added alone or in combination with 3 nM DAG during 12 h and 24 h. RESULTS: DAG has no effect on cell proliferation or viability, but it has an inhibitory effect on cell differentiation. DAG had a stimulatory effect on GSH-R1 expression at 12 and 24 h (p = 0.029 and p = 0.025, respectively). On the contrary, culture with 48 h DAG inhibits GSH-R1 expression compared to the control (p = 0.005), while GSH-R1 antagonist inhibited the effect of DAG on GSH-R1 expression. DAG also reduces intracellular (p = 0.020) and secreted (p = 0.011) hCG concentration in BeWo cells. CONCLUSION: DAG increases GHS-R1 expression, potentially mediated through GHS-R1 itself. DAG may also inhibit placental BeWo cell differentiation, suggesting a possible role of DAG in placental and fetal physiology.

Intersectionality in emotion signaling and recognition: The influence of gender, ethnicity, and social class.

Emotional expressions are a language of social interaction. Guided by recent advances in the study of expression and intersectionality, the present investigation examined how gender, ethnicity, and social class influence the signaling and recognition of 34 states in dynamic full-body expressive behavior. One hundred fifty-five Asian, Latinx, and European Americans expressed 34 emotional states with their full bodies. We then gathered 22,174 individual ratings of these expressions. In keeping with recent studies, people can recognize up to 29 full-body multimodal expressions of emotion. Neither gender nor ethnicity influenced the signaling or recognition of emotion, contrary to hypothesis. Social class, however, did have an influence: in keeping with past studies, lower class individuals proved to be more reliable signalers of emotion, and more reliable judges of full body expressions of emotion. Discussion focused on intersectionality and emotion. (PsycInfo Database Record (c) 2022 APA, all rights reserved).