Functional autoantibodies against G protein-coupled receptors in hepatic and pulmonary hypertensions in human schistosomiasis.

Introduction: Schistosomiasis (SM) is a parasitic disease caused by Schistosoma mansoni. SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM. Methods: Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123. Results: The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs. Conclusion: Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.

Chronology and social significance of the "princely" barrow cemetery in Leki Male and the Central European Early Bronze Age.

The "princely" barrows of Leki Male, Greater Poland are the oldest such monuments within the distribution area of Únetice societies in Central Europe. While in the Circum-Harz group and in Silesia similar rich furnished graves under mounds have appeared as single monuments as early as 1950 BC, Leki Male represents a chain of barrows constructed between 2150 BC and 1800 BC. Of the original 14 mounds, only four were preserved well enough that their complex biographies can now be reconstructed. They included ritual activities (before, during, and after the funeral), and also subsequent incursions, including robberies. The long lasting barrow cemetery at Leki Male can be linked to a nearby fortified site, Bruszczewo. Together, Leki Male and Bruszczewo represent a stable, socially differentiated society that existed for no less than 350-400 years. Therefore, it can be argued that the Early Bronze Age societies of Greater Poland were extremely sustainable in comparison to those of other Únetice regions.

Comparative skull osteology of Amphisbaena arda and Amphisbaena vermicularis (Squamata: Amphisbaenidae).

The skull anatomy of amphisbaenians directly influences their capacity to burrow and is crucial for the study of their systematics, which ultimately contributes to our comprehension of their evolution and ecology. In this study, we employed three-dimensional X-ray computed tomography to provide a detailed description and comprehensive comparison of the skull anatomy of two amphisbaenian species with similar external morphology, Amphisbaena arda and Amphisbaena vermicularis. Our findings revealed some differences between the species, especially in the sagittal crest of the parietal bone, the ascendant process, and the transverse occipital crest of the occipital complex. We also found intraspecific variation within A. vermicularis, with some specimens displaying morphology that differed from their conspecifics but not from A. arda. The observed intraspecific variation within A. vermicularis cannot be attributed to soil features because all specimens came from the same locality. Specimen size and soil type may play a role in the observed differences between A. arda and A. vermicularis, as the single A. arda specimen is the largest of our sample and soil type and texture differ between the collection sites of the two species.

Combining species distribution models and big datasets may provide finer assessments of snakebite impacts.

BACKGROUND: Snakebite is a major poverty-related neglected tropical disease. An integrated scientific approach is needed to understand the dynamics of this important health issue. Our objective was to estimate snakebite occurrence in a tropical area by using a blend of ecological modelling and robust statistical analysis. METHODS: The present study used climatic, environmental, and human population density data to determine the area with snakebite occurrence-probability for the first time in Bangladesh. We also analysed a large, 16-year dataset of hospitalized snakebite cases to reveal the epidemiology of snakebite in the south-eastern zone of the country. FINDINGS: Our results show that cobra bite is the most commonly occurring venomous snakebite in humans (around ~12% of the total yearly snakebite records), and men are more frequently bitten than women (2/3 of human victims are men). Most bites occur during the rainy season for cobra and green pit viper, while krait bites are not restricted to any particular season. As snakebite incidents are closely related to climate conditions, we can model snakebite risk using temperature and precipitation variables. Whereas there is a lack of snakebite reports from several parts of the study area in official records, our models predict that the entire study area is favourable for snakebite incidents. Based on the combined evidence we estimate that about 200,000 snakebite events occur every year in the south-eastern part of Bangladesh alone. Considering future global climate change, our model projections show that snakebite incidence in Bangladesh might not significantly decrease in the future (- 2070-); however, the distribution of probabilities might change, with a predicted increase of snakebite incidence in the hilly areas of the country. CONCLUSIONS: Using climatic data to predict snakebite incidence in Bangladesh allowed us to provide estimations of the total annual number of snakebite cases in the study area. As in most countries, the scarcity of accurate epidemiological data in official records might have masked the real magnitude of this problem. Our analysis suggests that the problem of snakebite envenoming in Bangladesh might be worse than currently perceived. A long-term sustainable snakebite program plan should be designed and institutionalized, considering climatic, geographical and human demographic variables, to obtain better data and facilitate the implementation of accurate snakebite management programs for this country.

Microcurrent-Mediated Modulation of Myofibroblasts for Cardiac Repair and Regeneration.

Cardiovascular diseases are a significant cause of illness and death worldwide, often resulting in myofibroblast differentiation, pathological remodeling, and fibrosis, characterized by excessive extracellular matrix protein deposition. Treatment options for cardiac fibrosis that can effectively target myofibroblast activation and ECM deposition are limited, necessitating an unmet need for new therapeutic approaches. In recent years, microcurrent therapy has demonstrated promising therapeutic effects, showcasing its translational potential in cardiac care. This study therefore sought to investigate the effects of microcurrent therapy on cardiac myofibroblasts, aiming to unravel its potential as a treatment for cardiac fibrosis and heart failure. The experimental design involved the differentiation of primary rat cardiac fibroblasts into myofibroblasts. Subsequently, these cells were subjected to microcurrent (MC) treatment at 1 and 2 µA/cm2 DC with and without polarity reversal. We then investigated the impact of microcurrent treatment on myofibroblast cell behavior, including protein and gene expression, by performing various assays and analyses comparing them to untreated myofibroblasts and cardiac fibroblasts. The application of microcurrents resulted in distinct transcriptional signatures and improved cellular processes. Gene expression analysis showed alterations in myofibroblast markers, extracellular matrix components, and pro-inflammatory cytokines. These observations show signs of microcurrent-mediated reversal of myofibroblast phenotype, possibly reducing cardiac fibrosis, and providing insights for cardiac tissue repair.

ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress.

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD.

A new sphenodontian (Diapsida: Lepidosauria) from the Upper Triassic (Norian) of Germany and its implications for the mode of sphenodontian evolution.

The Arnstadt Formation of Saxony-Anhalt, Germany has yielded some of Germany's most substantial finds of Late Triassic tetrapods, including the sauropodomorph Plateosaurus and the stem-turtle Proganochelys quenstedti. Here, we describe an almost complete skull of a new sphenodontian taxon from this formation (Norian, 227-208 Ma), making it the oldest known articulated sphenodontian skull from Europe and one of the oldest in the world. The material is represented by the dermal skull roof and by the complete maxilla and temporal region, as well as parts of the palate, braincase, and lower jaw. A phylogenetic assessment recovers it as a basal sphenodontian closely related to Planocephalosaurus robinsonae and to Eusphenodontia, making it the earliest-diverging sphenodontian known with an articulated skull. Its cranial anatomy is generally similar to the well-known Diphydontosaurus avonis from the Rhaetian of England, showing that this successful phenotype was already established in the clade around 10 myr earlier than assumed. An analysis of evolutionary change rates recovers high rates of evolution in basal sphenodontians, with decreasing rates throughout the evolution of the group. However, contrary to previous studies, reversals in this trend were identified, indicating additional peaks of evolutionary change. These results improve our understanding of the early sphenodontian diversity in Europe, providing critical information on evolutionary trends throughout the history of the clade and sparking renewed interest in its evolution.

Opinion Models, Election Data, and Political Theory.

A unifying setup for opinion models originating in statistical physics and stochastic opinion dynamics are developed and used to analyze election data. The results are interpreted in the light of political theory. We investigate the connection between Potts (Curie-Weiss) models and stochastic opinion models in the view of the Boltzmann distribution and stochastic Glauber dynamics. We particularly find that the q-voter model can be considered as a natural extension of the Zealot model, which is adapted by Lagrangian parameters. We also discuss weak and strong effects (also called extensive and nonextensive) continuum limits for the models. The results are used to compare the Curie-Weiss model, two q-voter models (weak and strong effects), and a reinforcement model (weak effects) in explaining electoral outcomes in four western democracies (United States, Great Britain, France, and Germany). We find that particularly the weak effects models are able to fit the data (Kolmogorov-Smirnov test) where the weak effects reinforcement model performs best (AIC). Additionally, we show how the institutional structure shapes the process of opinion formation. By focusing on the dynamics of opinion formation preceding the act of voting, the models discussed in this paper give insights both into the empirical explanation of elections as such, as well as important aspects of the theory of democracy. Therefore, this paper shows the usefulness of an interdisciplinary approach in studying real world political outcomes by using mathematical models.

The Superblock model: A review of an innovative urban model for sustainability, liveability, health and well-being.

INTRODUCTION: Current urban and transport planning practices have significant negative health, environmental, social and economic impacts in most cities. New urban development models and policies are needed to reduce these negative impacts. The Superblock model is one such innovative urban model that can significantly reduce these negative impacts through reshaping public spaces into more diverse uses such as increase in green space, infrastructure supporting social contacts and physical activity, and through prioritization of active mobility and public transport, thereby reducing air pollution, noise and urban heat island effects. This paper reviews key aspects of the Superblock model, its implementation and initial evaluations in Barcelona and the potential international uptake of the model in Europe and globally, focusing on environmental, climate, lifestyle, liveability and health aspects. METHODS: We used a narrative meta-review approach and PubMed and Google scholar databases were searched using specific terms. RESULTS: The implementation of the Super block model in Barcelona is slow, but with initial improvement in, for example, environmental, lifestyle, liveability and health indicators, although not so consistently. When applied on a large scale, the implementation of the Superblock model is not only likely to result in better environmental conditions, health and wellbeing, but can also contribute to the fight against the climate crisis. There is a need for further expansion of the program and further evaluation of its impacts and answers to related concerns, such as environmental equity and gentrification, traffic and related environmental exposure displacement. The implementation of the Superblock model gained a growing international reputation and variations of it are being planned or implemented in cities worldwide. Initial modelling exercises showed that it could be implemented in large parts of many cities. CONCLUSION: The Superblock model is an innovative urban model that addresses environmental, climate, liveability and health concerns in cities. Adapted versions of the Barcelona Superblock model are being implemented in cities around Europe and further implementation, monitoring and evaluation are encouraged. The Superblock model can be considered an important public health intervention that will reduce mortality and morbidity and generate cost savings for health and other sectors.

Brobdingnagians and Goliaths: two forms of gigantism in fish.

Two forms of gigantism are differentiated in fish, Brobdingnagian and Goliathan gigantism, the former applying to populations whose individuals are all larger than is typical for the taxon, the latter to single individuals within a population. While Brobdingnagian gigantism is largely explained by various ecological and evolutionary rules, Goliathan gigantism is not. A mechanistic hypothesis is proposed which explains Goliathan gigantism in terms of the reduction of oxygen requirements of individual fish via moving to cooler temperatures and/or acquiring larger, more energy-dense prey, which enable them to get bigger, and, in the process, sometimes generate bimodal size distributions that may qualify as gradual forms between Goliathan and Brobdingnagian gigantism. This mechanism, which relies on the manner in which their gill surface area grows, is more likely to operate in fish that can get big in the first place than in fish that remain small.

Transformation of cereal grains: Botanical and chemical analysis of food residues encrusted on pottery from the Funnel Beaker settlement of Oldenburg LA 77, northern Germany.

An integrated botanical and chemical approach is used to study surface residues on Funnel Beaker ceramics from the site of Oldenburg LA 77, in northern Germany. Organic residues were discovered adhering to fragments of thick-walled, undecorated ceramic vessels (n = 19) and ceramic discs (n = 2). The surface residues were studied using scanning electron microscopy (SEM), to examine remains of cereals and other plant tissues that survived food preparation and cooking, and using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and direct time-resolved mass spectrometry (DTMS), to chemically identify specific food components. The SEM results show a reoccurring presence of cereal grain (emmer and barley) and one case of co-occurrence of emmer and fat-hen seeds. The SEM evidence for the use of sprouted emmer grain and milk-ripe barley from the Oldenburg residues greatly enhances our understanding of Neolithic foodways in northwestern Europe. The ATR-FTIR results showed that roughly a third of the surface residues contain traces of the original foods prepared or processed and DTMS results confirm that most of the residues primarily contain polysaccharides and a minimal amount of plant protein and that they lack lipids. Only one residue presents minor indications for a (partly) animal origin. The ceramic vessels were thus used almost exclusively for the processing or cooking of cereal grains. This study offers an intimate view of the cuisine and cooking practices (and in some cases their seasonal timing) in an early agricultural village located in a marginal farming region on the south coast of the Baltic Sea.

The rostral micro-tooth morphology of blue marlin, Makaira nigricans.

Billfish rostra potentially have several functions; however, their role in feeding is unequivocal in some species. Recent work linked morphological variation in rostral micro-teeth to differences in feeding behavior in two billfish species, the striped marlin (Kajikia audax) and the sailfish (Istiophorus platypterus). Here, we present the rostral micro-tooth morphology for a third billfish species, the blue marlin (Makaira nigricans), for which the use of the rostrum in feeding behavior is still undocumented from systematic observations in the wild. We measured the micro-teeth on rostrum tips of blue marlin, striped marlin, and sailfish using a micro-computed tomography approach and compared the tooth morphology among the three species. This was done after an analysis of video-recorded hunting behavior of striped marlin and sailfish revealed that both species strike prey predominantly with the first third of the rostrum, which provided the justification to focus our analysis on the rostrum tips. In blue marlin, intact micro-teeth were longer compared to striped marlin but not to sailfish. Blue marlin had a higher fraction of broken teeth than both striped marlin and sailfish, and broken teeth were distributed more evenly on the rostrum. Micro-tooth regrowth was equally low in both marlin species but higher in sailfish. Based on the differences and similarities in the micro-tooth morphology between the billfish species, we discuss potential feeding-related rostrum use in blue marlin. We put forward the hypothesis that blue marlin might use their rostra in high-speed dashes as observed in striped marlin, rather than in the high-precision rostral strikes described for sailfish, possibly focusing on larger prey organisms.

HBM4EU chromates study - PFAS exposure in electroplaters and bystanders.

The study aims to reveal the exposure to perfluoroalkyl substances (PFAS) in workers in different industry sectors with exposures to hexavalent chromium (Cr(VI)). The PFAS exposure of in total 172 individuals from 4 countries was assessed by the determination of 8 perfluoroalkyl carboxylic acids and 4 perfluoroalkyl sulfonic acids in plasma samples. The participants were 52 chrome plating workers, 43 welders, 3 surface treating workers and 74 workers without any occupational Cr exposure as controls. Significant differences between workers with Cr exposure and controls were found for the perfluoroalkyl sulfonic acids, particularly for perfluorooctane sulfonic acid (PFOS). The median and maximum levels were, respectively, 4.83 and 789 µg/l for chrome plating workers, 4.97 and 1513 µg/l for welders, and 3.65 and 13.9 µg/l for controls. The considerably high PFOS exposure in Cr platers and welders can be explained by the former application of PFOS as mist suppressants in electroplating baths, which resulted in an exposure of the directly involved operators, but also of welders performing maintenance and repair service at these workplaces.

Endoscopic negative-pressure treatment : From management of complications to pre-emptive active reflux drainage in abdomino-thoracic esophageal resection-A new safety concept for esophageal surgery.

INTRODUCTION: Early postoperative reflux (PR) can compromise anastomotic healing after Ivor Lewis esophagectomy (ILE) and poses a risk for aspiration. Anastomotic insufficiency is the most threatening surgical complication. We present the protective method of pre-emptive active reflux drainage (PARD) with simultaneous enteral feeding. We report our experience with this new safety concept in esophageal surgery in a cohort of 43 patients. MATERIALS AND METHODS: For PARD we use a double lumen open porous film drainage (dOFD). To create the dOFD, the gastric tube of a Trelumina probe (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore drainage film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over a length of 25 cm. The dOFD is endoscopically inserted into the tubular stomach intraoperatively after completion of the anastomosis. Continuous negative pressure is applied with an electronic pump (-125 mm Hg). The PR is continuously aspirated completely and the stomach and anastomotic region are decompressed. At the same time, nutrition is delivered via an integrated intestinal tube. Depending on the results of the endoscopic control after 5 days, PARD is either continued or terminated. RESULTS: During the observation period (2017-2023), PARD was used in all patients (n = 43) with ILE. The healing rate under PARD was 100% and healing was observed in all anastomoses. No additional endoscopic procedures or surgical revisions of the anastomoses were required. The median duration of PARD was 8 days (range 4-21). We observed problems in the healing of the anastomosis in 20 of 43 patients (47%) for whom we defined endoscopic criteria for at-risk anastomosis. CONCLUSIONS: Our results suggest that PARD has a strong protective effect on anastomotic healing and may reduce the risk of anastomotic insufficiency. The integrated feeding tube of the dOFD allows early postoperative enteral feeding while simultaneously applying negative pressure. PARD appears to prevent the negative consequences of impaired anastomotic healing.

Isotopes prove advanced, integral crop production, and stockbreeding strategies nourished Trypillia mega-populations.

After 500 y of colonizing the forest-steppe area northwest of the Black Sea, on the territories of what is today Moldova and Ukraine, Trypillia societies founded large, aggregated settlements from ca. 4150 BCE and mega-sites (>100 ha) from ca. 3950 BCE. Covering up to 320 ha and housing up to 15,000 inhabitants, the latter were the world's largest settlements to date. Some 480 δ13C and δ15N measurements on bones of humans, animals, and charred crops allow the detection of spatio-temporal patterns and the calculation of complete agricultural Bayesian food webs for Trypillia societies. The isotope data come from settlements of the entire Trypillia area between the Prut and the Dnieper rivers. The datasets cover the development of the Trypillia societies from the early phase (4800-4200/4100 BCE), over the agglomeration of mega-sites (4200/4100-3650 BCE), to the dispersal phase (3650-3000 BCE). High δ15N values mostly come from the mega-sites. Our analyses show that the subsistence of Trypillia mega-sites depended on pulses cultivated on strongly manured (dung-)soils and on cattle that were kept fenced on intensive pastures to easy collect the manure for pulse cultivation. The food web models indicate a low proportion of meat in human diet (approximately 10%). The largely crop-based diet, consisting of cereals plus up to 46% pulses, was balanced in calories and indispensable amino acids. The flourishing of Europe's first mega-populations depended on an advanced, integral mega-economy that included sophisticated dung management. Their demise was therefore not economically, but socially, conditioned [Hofmann et al., PLoS One. 14, e0222243 (2019)].

Physical, Mental, and Social Health of Incarcerated Men: The Relevance of Organized and Informal Sports Activities.

Previous research indicates general health benefits of sport for imprisoned individuals. Nevertheless, the role of time spent in sporting activities during imprisonment and the type of sports setting (informal vs. organized) remain unclear. The study uses a quantitative, cross-sectional design. It is based on survey data (N = 568) from the Hessian Prison Sport Study, collected in 12 prisons in Hesse, Germany. By applying regression analyses, the study examines systematic relationships between time spent in sporting activities and incarcerated people's physical, mental, and social health. It also investigates to what extent participation in informal and organized sports is correlated with various health indicators. Results show that higher levels of physical activity (≥5 hours/week) in prison are associated with all health indicators investigated. Incarcerated individuals who regularly engage in informal and organized sports report significantly better health than inactive individuals. Although informal sports yield certain health benefits, only organized sport is associated with higher social connectedness. In addition to confirming the biopsychosocial health benefits of regular sporting activity for imprisoned individuals, the findings highlight that informal and organized sports activities are both important for promoting health.

Parameter estimation for contact tracing in graph-based models.

We adopt a maximum-likelihood framework to estimate parameters of a stochastic susceptible-infected-recovered (SIR) model with contact tracing on a rooted random tree. Given the number of detectees per index case, our estimator allows to determine the degree distribution of the random tree as well as the tracing probability. Since we do not discover all infectees via contact tracing, this estimation is non-trivial. To keep things simple and stable, we develop an approximation suited for realistic situations (contract tracing probability small, or the probability for the detection of index cases small). In this approximation, the only epidemiological parameter entering the estimator is R0. The estimator is tested in a simulation study and is furthermore applied to COVID-19 contact tracing data from India. The simulation study underlines the efficiency of the method. For the empirical COVID-19 data, we compare different degree distributions and perform a sensitivity analysis. We find that particularly a power-law and a negative binomial degree distribution fit the data well and that the tracing probability is rather large. The sensitivity analysis shows no strong dependency of the estimates on the reproduction number. Finally, we discuss the relevance of our findings.

Prisoners' Educational Experiences in Five Different Prison Sports Programmes: A Research Note.

Organized sports programmes offer manifold opportunities for learning and personal development. Prisoners in organized sports programmes could profit from these educational opportunities, which could eventually support their process of reintegration into society. However, research on the educational experiences of imprisoned individuals during organized sports activities is scarce. Using quantitative survey data (N = 568 adult male prisoners) collected within the scope of the Hessian Prison Sports Study in Hesse, Germany, the present study examines educational experiences that are instigated through participation in five different prison sports programmes (fitness, racket, and team sports, running groups, and strength training). The results show that participants reported few educational experiences. The most common experiences reported were learning to exert effort and acquiring health-related knowledge. The findings reveal distinct patterns for specific sports programmes. For instance, team sports more frequently address cooperation skills and fairness. This paper advocates for more attention to the educational potential of sports in prison settings, where sports outcomes should be better aligned with the desired educational outcomes.