Emx2 underlies the development and evolution of marsupial gliding membranes.

Phenotypic variation among species is a product of evolutionary changes to developmental programs1,2. However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium-an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.

The Effect of Clothes on Blood Pressure Measurement in Normotensive and Hypertensive Subjects in a Real-Life Setting.

INTRODUCTION: The effect of clothing on the recording of blood pressure in a normotensive and hypertensive population remains essential to diagnosing and managing. METHODS: This is a cross-sectional study to measure blood pressure using a validated oscillometric sphygmomanometer in two populations. The records were made over the thicker sleeve arm and non-sleeved arm (either on bare arm or indicating the removal of the outermost garment). Clothing was categorized according to how patients attended the outpatient clinic based on the real world. RESULTS: A total of 75 patients were included with a diagnosis of hypertension whose mean age was 67.1 years (SD ± 16.3). The group of normotension included 63 patients whose mean age was 21.1 years (SD ± 2.2). There was not variability related to technique or inherent to the condition of the subject on the first and second measurements of blood pressure. In the comparative analysis, the group with normotension did not report a significant difference in systolic or diastolic blood pressure due to the effect of clothing during the first or second measurement (p > 0.05). In the group with hypertension, a significant difference was observed in the first measurement, between the group over-the-sleeve and non-sleeved arm (systolic blood pressure, p: 0.021 and diastolic, p: 0.001). However, when the variable order of measurement was analyzed by randomizing the initial registry with or without clothing was not found a statistical difference. CONCLUSION: Clothing does not a significant difference in the measure of blood pressure in a normotensive or hypertensive population.

The GRN concept as a guide for evolutionary developmental biology.

Organismal phenotypes result largely from inherited developmental programs, usually executed during embryonic and juvenile life stages. These programs are not blank slates onto which natural selection can draw arbitrary forms. Rather, the mechanisms of development play an integral role in shaping phenotypic diversity and help determine the evolutionary trajectories of species. Modern evolutionary biology must, therefore, account for these mechanisms in both theory and in practice. The gene regulatory network (GRN) concept represents a potent tool for achieving this goal whose utility has grown in tandem with advances in "omic" technologies and experimental techniques. However, while the GRN concept is widely utilized, it is often less clear what practical implications it has for conducting research in evolutionary developmental biology. In this Perspective, we attempt to provide clarity by discussing how experiments and projects can be designed in light of the GRN concept. We first map familiar biological notions onto the more abstract components of GRN models. We then review how diverse functional genomic approaches can be directed toward the goal of constructing such models and discuss current methods for functionally testing evolutionary hypotheses that arise from them. Finally, we show how the major steps of GRN model construction and experimental validation suggest generalizable workflows that can serve as a scaffold for project design. Taken together, the practical implications that we draw from the GRN concept provide a set of guideposts for studies aiming at unraveling the molecular basis of phenotypic diversity.

Assessing synergies and trade-offs of diverging Paris-compliant mitigation strategies with long-term SDG objectives.

The Sustainable Development Goals (SDGs) and the Paris Agreement are the two transformative agendas, which set the benchmarks for nations to address urgent social, economic and environmental challenges. Aside from setting long-term goals, the pathways followed by nations will involve a series of synergies and trade-offs both between and within these agendas. Since it will not be possible to optimise across the 17 SDGs while simultaneously transitioning to low-carbon societies, it will be necessary to implement policies to address the most critical aspects of the agendas and understand the implications for the other dimensions. Here, we rely on a modelling exercise to analyse the long-term implications of a variety of Paris-compliant mitigation strategies suggested in the recent scientific literature on multiple dimensions of the SDG Agenda. The strategies included rely on technological solutions such as renewable energy deployment or carbon capture and storage, nature-based solutions such as afforestation and behavioural changes in the demand side. Results for a selection of energy-environment SDGs suggest that some mitigation pathways could have negative implications on food and water prices, forest cover and increase pressure on water resources depending on the strategy followed, while renewable energy shares, household energy costs, ambient air pollution and yield impacts could be improved simultaneously while reducing greenhouse gas emissions. Overall, results indicate that promoting changes in the demand side could be beneficial to limit potential trade-offs.

Intra-observer reproducibility and inter-observer agreement of Fels skeletal age assessments among male tennis players 8-16 years.

BACKGROUND: Skeletal age (SA) is an estimate of biological maturity status that is commonly used in sport-related medical examinations. This study considered intra-observer reproducibility and inter-observer agreement of SA assessments among male tennis players. METHODS: SA was assessed with the Fels method in 97 male tennis players with chronological ages (CA) spanning 8.7-16.8 years. Radiographs were evaluated by two independent trained observers. Based on the difference between SA and CA, players were classified as late, average or early maturing; if a player was skeletally mature, he was noted as such as an SA is not assigned. RESULTS: The magnitude of intra-individual differences between repeated SA assessments were d = 0.008 year (observer A) and d = 0.001 year (observer B); the respective coefficients of variation were 1.11% and 1.75%. Inter-observer mean differences were negligible (t = 1.252, p = 0.210) and the intra-class correlation coefficient was nearly perfect (ICC = 0.995). Concordance of classifications of players by maturity status between observers was 90%. CONCLUSION: Fels SA assessments were highly reproducible and showed an acceptable level of inter-observer agreement between trained examiners. Classifications of players by skeletal maturity status based on assessments of the two observers were highly concordant, though not 100%. The results highlight the importance of experienced observers in skeletal maturity assessments.

The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

The malaria burden of Amerindian groups of three Venezuelan states: a descriptive study based on programmatic data.

BACKGROUND: Fifty-three percent of all cases of malaria in the Americas in 2019 came from Venezuela, where the epidemic is heavily focused south of the Orinoco river, and where most of the country's Amerindian groups live. Although the disease is known to represent a significant public health problem among these populations, little epidemiological data exists on the subject. This study aims to provide information on malaria incidence, geospatial clustering, and risk factors associated to Plasmodium falciparum infection among these groups. METHODS: This is a descriptive study based on the analysis of published and unpublished programmatic data collected by Venezuelan health authorities and non-government organizations between 2014 and 2018. The Annual Parasite Index among indigenous groups (API-i) in municipalities of three states (Amazonas, Bolivar, and Sucre) were calculated and compared using the Kruskal Wallis test, risk factors for Plasmodium falciparum infection were identified via binomial logistic regression and maps were constructed to identify clusters of malaria cases among indigenous patients via Moran's I and Getis-Ord's hot spot analysis. RESULTS: 116,097 cases of malaria in Amerindian groups were registered during the study period. An increasing trend was observed between 2014 and 2016 but reverted in 2018. Malaria incidence remains higher than in 2014 and hot spots were identified in the three states, although more importantly in the south of Bolivar. Most cases (73.3%) were caused by Plasmodium vivax, but the Hoti, Yanomami, and Eñepa indigenous groups presented higher odds for infection with Plasmodium falciparum. CONCLUSION: Malaria cases among Amerindian populations increased between 2014 and 2018 and seem to have a different geographic distribution than those among the general population. These findings suggest that tailored interventions will be necessary to curb the impact of malaria transmission in these groups.

Toenails as a biomarker of exposure to arsenic: A review.

This systematic review summarizes the current evidence related to the reliability of toenail total arsenic concentrations (thereafter "arsenic") as a biomarker of long-term exposure. Specifically, we reviewed literature on consistency of repeated measures over time, association with other biomarkers and metal concentrations, factors influencing concentrations, and associations with health effects. We identified 129 papers containing quantitative original data on arsenic in toenail samples covering populations from 29 different countries. We observed geographic differences in toenail arsenic concentrations, with highest median or mean concentrations in Asian countries. Arsenic-contaminated drinking water, occupational exposure or living in specific industrial areas were associated with an increased toenail arsenic content. The effects of other potential determinants and sources of arsenic exposure including diet, gender and age on the concentrations in toenails need further investigations. Toenail arsenic was correlated with the concentrations in hair and fingernails, and with urine arsenic mainly among highly exposed populations with a toenail mean or median ≥1 µg/g. Overall, there is a growing body of evidence suggesting that arsenic content from a single toenail sample may reflect long-term internal dose-exposure. Toenail arsenic can serve as a reliable measure of toxic inorganic arsenic exposure in chronic disease research, particularly promising for cancer and cardiovascular conditions.

Measurement of morphology thickness and refractive index in a melanoma A375 cell line using digital holographic microscopy.

Digital holographic microscopy (DHM) is a technique that has high potential for analyzing biological samples and has been successfully applied to the study of cells and cell lines providing information about important parameters such as refractive index, morphology, and dry mass, among others; it has also found applicability to study the effects of therapeutic treatments. Finding the size and shape of cells is important since they tend to change in the presence of some pathologies. In this research work, we obtain the morphology thickness and refractive index of the A375 melanoma cell line through a slight tilting of the cell in a DHM setup. Further, the development of a novel mathematical expression based on this tilt and in the optical phase difference is presented. We show images of melanoma cells with the refractive index information included, and their morphology thickness as rendered from the holographic phase maps recorded with DHM.

Validation of an Electronic Visual Analog Scale mHealth Tool for Acute Pain Assessment: Prospective Cross-Sectional Study.

BACKGROUND: Accurate measurement of pain is required to improve its management and in research. The visual analog scale (VAS) on paper format has been shown to be an accurate, valid, reliable, and reproducible way to measure pain intensity. However, some limitations should be considered, some of which can be implemented with the introduction of an electronic VAS version, suitable to be used both in a tablet and a smartphone. OBJECTIVE: This study aimed to validate a new method of recording pain level by comparing the traditional paper VAS with the pain level module on the newly designed Interactive Clinics app. METHODS: A prospective observational cross-sectional study was designed. The sample consisted of 102 participants aged 18 to 65 years. A Force Dial FDK 20 algometer (Wagner Instruments) was employed to induce mild pressure symptoms on the participants' thumbs. Pain was measured using a paper VAS (10 cm line) and the app. RESULTS: Intermethod reliability estimated by ICC(3,1) was 0.86 with a 95% confidence interval of 0.81 to 0.90, indicating good reliability. Intramethod reliability estimated by ICCa(3,1) was 0.86 with a 95% confidence interval of 0.81 to 0.90, also indicating good reliability. Bland-Altman analysis showed a difference of 0.175 (0.49), and limits of agreement ranged from -0.79 to 1.14. CONCLUSIONS: The pain level module on the app is highly reliable and interchangeable with the paper VAS version. This tool could potentially help clinicians and researchers precisely assess pain in a simple, economic way with the use of a ubiquitous technology.

Comparison of a Mobile Health Electronic Visual Analog Scale App With a Traditional Paper Visual Analog Scale for Pain Evaluation: Cross-Sectional Observational Study.

BACKGROUND: Accurate quantification of pain in a clinical setting is vital. The use of an electronic pain scale enables data to be collected, analyzed, and utilized much faster compared with traditional paper-based scales. The advancement of smart technology in pediatric and adult pain evaluation may offer opportunities to introduce easy-to-use and reliable pain assessment methods within different clinical settings. If promptly introduced within different pediatric and adult pain clinic services, validated and easily accessible mobile health pain apps may lead to early pain detection, promoting improvement in patient's quality of life and leading to potentially less time off from school or work. OBJECTIVE: This cross-sectional observational study aimed to investigate the interchangeability of an electronic visual analog scale (eVAS) app with a traditional paper visual analog scale (pVAS) among Australian children, adolescents, and adults for pain evaluation. METHODS: Healthy participants (age range 10-75 years) were recruited from a sporting club and a secondary school in Melbourne (Australia). The data collection process involved application of pressure (8.5 kg/cm2) from a Wagner Force Dial FDK 20 to the midpoint of the thumb. The pressure was applied twice with a 5-minute interval. At each pressure application, participants were asked to randomly record their pain perception using the "eVAS" accessible via the "Interactive Clinics" app and the traditional pVAS. Statistical analysis was conducted to determine intermethod and intramethod reliabilities. RESULTS: Overall, 109 healthy participants were recruited. Adults (mean age 42.43 years, SD 14.50 years) had excellent reliability, with an intraclass correlation coefficient (ICC) of 0.94 (95% CI 0.91-0.96). Children and adolescents (mean age 13.91 years, SD 2.89 years) had moderate-to-good intermethod and intramethod reliabilities, with an ICC of 0.80 (95% CI 0.70-0.87) and average ICC of 0.80 (95% CI 0.69-0.87), respectively. CONCLUSIONS: The eVAS app appears to be interchangeable compared with the traditional pVAS among children, adolescents, and adults. This pain evaluation method may offer new opportunities to introduce user-friendly and validated pain assessment apps for patients, clinicians, and allied health professionals.

Molecular Detection and Species Determination of Malaria Parasites, Venezuela.

In southeastern Venezuela, malaria cases have increased since 2013. We found that 46% of 352 blood samples from symptomatic patients in 1 municipality tested positive for Plasmodium spp. In addition, the number of cases increased by 10 times in 4 years (2014-2017) and by 3 times in 1 year (2016-2017).

A high number of pfmdr1 gene copies in P. falciparum from Venezuela.

Multidrug resistance in Plasmodium falciparum has been associated with gene amplification of pfmdr1. We studied the corresponding gene amplification in P. falciparum from blood samples of malaria patients in the Sifontes Municipality, Bolívar State, Venezuela, known as the highest region of incidence of malaria. Fifty-five P. falciparum DNA samples were extracted from different hosts and used for qPCR assessment of the copy number of pfmdr1. The assay detected four copies of the multidrug-resistant line P. falciparum Dd2 in comparison with the P. falciparum 3D7 that had only one copy. In the patients' samples, the copy number of pfmdr1 was a single copy in 80% and 20% left distributed in different copy numbers up to seven.

A Wearable Textile 3D Gesture Recognition Sensor Based on Screen-Printing Technology.

Research has developed various solutions in order for computers to recognize hand gestures in the context of human machine interface (HMI). The design of a successful hand gesture recognition system must address functionality and usability. The gesture recognition market has evolved from touchpads to touchless sensors, which do not need direct contact. Their application in textiles ranges from the field of medical environments to smart home applications and the automotive industry. In this paper, a textile capacitive touchless sensor has been developed by using screen-printing technology. Two different designs were developed to obtain the best configuration, obtaining good results in both cases. Finally, as a real application, a complete solution of the sensor with wireless communications is presented to be used as an interface for a mobile phone.

Integration of a 2D Touch Sensor with an Electroluminescent Display by Using a Screen-Printing Technology on Textile Substrate.

Many types of solutions have been studied and developed in order to give the user feedback when using touchpads, buttons, or keyboards in textile industry. Their application on textiles could allow a wide range of applications in the field of medicine, sports or the automotive industry. In this work, we introduce a novel solution that combines a 2D touchpad with an electroluminescent display (ELD). This approach physically has two circuits over a flexible textile substrate using the screen-printing technique for wearable electronics applications. Screen-printing technology is widely used in the textile industry and does not require heavy investments. For the proposed solution, different layer structures are presented, considering several fabric materials and inks, to obtain the best results.

Morphological, Mechanical and Mucoadhesive Properties of Electrospun Chitosan/Phospholipid Hybrid Nanofibers.

This study aimed to develop hybrid electrospun chitosan⁻phospholipid nanofibers and investigate the effect of phospholipid (P) content and chitosans (Ch) molecular weights (Mw) and degree of acetylation (DA), on the morphological, mechanical and mucoadhesive properties of the nanofibers. Electrospun Ch/P nanofibers exhibited a smooth and uniform surface with average diameters ranging from 300 to 1000 nm, as observed by scanning electron microscopy (SEM). The average diameter of the nanofibers was observed to increase with the increase of the Mw and degree of deacetylation of Ch, and phospholipid content. The elastic and adhesive properties of the nanofibers were determined by atomic force microscopy, and displayed higher values for higher Mw and lower DA Ch used. The elastic modulus of electrospun Ch/P hybrid fibers determined for the different conditions tested was found to be in the range of 500 and 1400 MPa. Furthermore, electrospun Ch/P nanofibers displayed mucoadhesive properties expressed by the work of adhesion calculated after the compression of the nanofibers against a section of pig small intestine. Our results showed that the increase in phospholipid content and DA of Ch decrease the work of adhesion, while the increase of Mw resulted in slightly higher work of adhesion of the nanofibers.

Preparation and Characterization of an Oral Vaccine Formulation Using Electrosprayed Chitosan Microparticles.

Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil-A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a solvent. Three different chitosans designed as HMC+70, HMC+85, and HMC+90 (called as 705010, 855010, and 905010) were tested and its efficacy to be used in oral vaccine delivery applications was investigated. The morphology, size, and zeta potential of the produced particles were investigated, together with the encapsulation efficiency and release of OVA from the three chitosan formulations. Moreover, the mucoadhesion and cytotoxicity of the chitosan microparticles was examined. All the three formulations with OVA and Quil-A were in the micrometer size range and had a positive zeta potential between 46 and 75 mV. Furthermore, all the three formulations displayed encapsulation efficiencies above 80% and the release of OVA over a period of 80 h was observed to be between 38 and 47%. None of the developed formulations exhibited high mucoadhesive properties, either cytotoxicity. The formulation prepared with HMC+70, OVA, and Quil-A had the highest stability within 2 h in buffer solution, as measured by dynamic light scattering. The electrosprayed formulation consisting of HMC+70 with OVA and Quil-A showed to be the most promising as an oral vaccine system.

The role of isolation on contrasting phylogeographic patterns in two cave crustaceans.

BACKGROUND: The underlying mechanisms and processes that prompt the colonisation of extreme environments, such as caves, constitute major research themes of evolutionary biology and biospeleology. The special adaptations required to survive in subterranean environments (low food availability, hypoxic waters, permanent darkness), and the geographical isolation of caves, nominate cave biodiversity as ideal subjects to answer long-standing questions concerning the interplay amongst adaptation, biogeography, and evolution. The present project aims to examine the phylogeographic patterns exhibited by two sympatric species of surface and cave-dwelling peracarid crustaceans (Asellus aquaticus and Niphargus hrabei), and in doing so elucidate the possible roles of isolation and exaptation in the colonisation and successful adaptation to the cave environment. RESULTS: Specimens of both species were sampled from freshwater hypogean (cave) and epigean (surface) habitats in Hungary, and additional data from neighbouring countries were sourced from Genbank. Sequencing of mitochondrial and nuclear loci revealed, through haplotype network reconstruction (TCS) and phylogenetic inference, the genetic structure, phylogeographic patterns, and divergence-time estimates of A. aquaticus and N. hrabei surface and cave populations. Contrasting phylogeographic patterns were found between species, with A. aquaticus showing strong genetic differentiation between cave and surface populations and N. hrabei lacking any evidence of genetic structure mediated by the cave environment. Furthermore, N. hrabei populations show very low levels of genetic differentiation throughout their range, which suggests the possibility of recent expansion events over the last few thousand years. CONCLUSIONS: Isolation by cave environment, rather than distance, is likely to drive the genetic structuring observed between immediately adjacent cave and surface populations of A. aquaticus, a predominantly surface species with only moderate exaptations to subterranean life. For N. hrabei, in which populations exhibit a fully 'cave-adapted' (troglomorphic) phenotype, the lack of genetic structure suggests that subterranean environments do not pose a dispersal barrier for this surface-cave species.