BACKGROUND:Mesoamerican nephropathy is a public health crisis in young men in Central America. The disease does not share risk factors of chronic kidney disease (i.e. diabetes and hypertension) commonly seen in the U.S. Exposure to nephrotoxic agrochemicals is a hypothesized contributor to disease, but individual-level exposure measurements are lacking, as are analyses of exposures and outcomes. OBJECTIVES:Measure associations between urinary pesticides and kidney function within the Mesoamerican Nephropathy Occupational Study, a cohort of male workers aged 18-45 in Nicaragua and El Salvador. METHODS:Urine from 285 participants at two timepoints, enrollment and one year later, was analyzed for glyphosate and AMPA using HPLC-MS/MS. Urine of 50 participants from enrollment was also analyzed for four organophosphate, two phenoxy acid, and five pyrethroid pesticide metabolites using HPLC-MS/MS. We estimated associations between urinary pesticides and agrochemical jobs and estimated glomerular filtration rate (eGFR) cross-sectionally, over one year, and over the study period (two-and-a-half years in Nicaragua; three years in El Salvador). RESULTS:Higher urine glyphosate levels were associated with lower eGFR over one year, with significant associations for the lower exposure group (≤median): -4.0 mL/min/1.73 m2 (95% CI: -7.2, -0.87 mL/min/1.73 m2). However, participants with detectable urine glyphosate at both time points had lower odds of at least a 10% decline in eGFR decline over the study period (OR 0.33; 95% CI: 0.16, 0.65). The protective effect in our longer-term model may reflect healthy worker bias. Meanwhile, having an agrochemical job was significantly associated with higher odds of at least a 20% decline in eGFR over the study period (OR 1.7; 95% CI: 1.3, 2.3). SIGNIFICANCE:Urine pesticide levels were not consistently associated with reduced kidney function. 59 Having an agrochemical job was a predictor of kidney function decline. Other agricultural exposures, either individually or in combination with pesticides, may drive disease risks observed in this population. IMPACT:We evaluated urine concentrations of pesticides, including glyphosate, in a cohort of male workers in five industries (brickmaking, road construction, corn, plantain, and sugarcane) in El Salvador and Nicaragua, an area with endemic Mesoamerican nephropathy and where pesticide biomonitoring data in general is lacking. We found weak and limited evidence of associations between urinary glyphosate or other pesticide levels and change in kidney function. However, we observed a significant positive association between having an agrochemical job and kidney decline over the study period.

Exposure to elements such as arsenic, cadmium, lead, and mercury, which are associated with cancer, cardiovascular disease, and kidney disease, are not well-studied in Central American populations. We evaluated differences in urine metal(loid) concentrations by dietary/behavioral, occupational, and geographic factors within a cohort of adult male workers in El Salvador in the MesoAmerican Nephropathy Occupational Study (MANOS). We measured spot urinary concentrations of 14 metal(loid)s and speciated arsenic in 194 participants in 2021. We compared concentrations in our study to the US National Health and Nutrition Examination Survey (NHANES) data. We used multiple linear regression to examine known metal(loid) exposure sources (e.g. smoking and seafood consumption) and the role of occupational and geographic-related predictors (e.g. industry and region) in association with urinary metal(loid) concentrations. We detected 13 of 14 metal(loid)s and all targeted biomarkers of arsenic species in participants' urine samples, with detection frequencies ranging from 4-100%. Compared to NHANES data, MANOS participants had significantly higher (p<0.05) median concentrations (& micro;g/L) of all arsenic species (sum of inorganic arsenic species 10 vs. 54), cobalt (0.39 vs. 0.030), and thallium (0.27 vs. 0.20), while molybdenum and uranium were significantly lower in MANOS (35 vs. 49 and 0.0035 vs. 0.75, respectively). Arsenobetaine concentrations were 140% higher (95% CI: 58, 260%) in recent seafood consumers. Among smokers, cadmium and lead were 57% (95% CI: 21, 102) and 38% higher (95% CI: 3, 85), respectively. The sum of inorganic arsenic species was 48% higher (95% CI: 24, 77), while mercury and lead were-30% (95% CI:-48,-6.4) and-43% (95% CI:-59,-22) lower in sugarcane workers compared to corn workers. Compared to participants with normal kidney function, indicated by estimated glomerular filtration rate (eGFR) >90 ml/min/1.73m(2), participants with higher Ba, Cs, Pb, and Tl concentrations had lower kidney function, while those with higher Mn and U had higher kidney function. Findings suggest dietary, renal, and workplace factors influence some metal(loid) exposures in El Salvador. Understanding sources of metal(loid) concentrations may help identify strategies to reduce exposures and accompanying health risks.

BACKGROUND:Chronic kidney disease of unknown etiology (CKDu) is a major health concern among outdoor manual workers in rural Central America and South Asia. The CURE study is a prospective longitudinal cohort designed to investigate CKDu's environmental risk factors through standardized exposure assessments, questionnaires, and biological and environmental sample collection. METHODS:This manuscript details the development of a standardized exposure assessment protocol within the CKDu CURE Consortium. The study recruits adults (18-45 years) from CKDu hotspots across five countries, ensuring proportional representation across three eGFR categories (20-59, 60-89, ≥90 mL/min/1.73m2) and excluding participants with diabetes or other known CKD causes. The CURE study is committed to promptly returning clinically and environmentally relevant test results to participants after analysis. RESULTS:Exposure assessment includes demographics, healthcare access, nephrotoxic medications, infectious pathogens, and agricultural work conditions (e.g., heat stress, hydration, diet, agrochemicals, toxicants). Biological and environmental samples (water, dust, soil, wristbands) are collected considering seasonal variations. Omics analyses, including metabolomics, will investigate environmental and biological interactions. Statistical analyses will assess relationships between exposures and CKDu onset or progression, incorporating environmental mixture analyses. CONCLUSION:CURE will provide critical insights into CKDu risk factors, supporting future research and prevention strategies. A comprehensive exposure assessment will enhance understanding of environmental contributors, guiding interventions at individual, workplace, and community levels to mitigate CKDu's impact.

ABSTRACT Coping with the impacts of global climate change on the biosphere in general and humanity in particular requires that we shift attention from economic principles of sustainability to evolutionary principles of survival. Darwinism provides a third way between unattainable utopia and unacceptable apocalypse. The Four Laws of Biotics provide Darwinian guidelines for interacting with the biosphere and improving humanity’s chances of survival as a technological species. The biosphere is a complex evolutionary system comprising species that generate, store, and use their own potential to survive. This allows the biosphere to continue to cope with change by changing, making ecosystems robust, not fragile. This is the only means by which the biosphere has survived previous episodes of climate change, and it has never failed. Conservation policies need to shift from treating the biosphere as a material commons to treating the biosphere as an evolutionary commons. Within a survivable biosphere, humanity’s future can be enhanced by (1) implementing the economics of well-being, (2) reducing population density through climate migration into rural areas, revitalizing them into circularized economies, (3) re-growing sustainably by creating networks of cooperating circular economies, not consolidating into densely populated urban centers, and (4) ensuring social institutions are responsive to the desires of the grassroots. Technological urbanized humans can alter their behavior now at great expense and difficulty, extending the benefits of the Anthropocene, or can fail to act, and face imminent collapse.

How humanity brought about the climate crisis by departing from its evolutionary trajectory 15,000 years ago—and how we can use evolutionary principles to save ourselves from the worst outcomes. Despite efforts to sustain civilization, humanity faces existential threats from overpopulation, globalized trade and travel, urbanization, and global climate change. In A Darwinian Survival Guide, Daniel Brooks and Salvatore Agosta offer a novel—and hopeful—perspective on how to meet these tremendous challenges by changing the discourse from sustainability to survival. Darwinian evolution, the world's only theory of survival, is the means by which the biosphere has persisted and renewed itself following past environmental perturbations, and it has never failed, they explain. Even in the aftermath of mass extinctions, enough survivors remain with the potential to produce a new diversified biosphere. Drawing on their expertise as field biologists, Brooks and Agosta trace the evolutionary path from the early days of humans through the Late Pleistocene and the beginning of the Anthropocene all the way to the Great Acceleration of technological humanity around 1950, demonstrating how our creative capacities have allowed humanity to survive. However, constant conflict without resolution has made the Anthropocene not only unsustainable, but unsurvivable. Guided by the four laws of biotics, the authors explain how humanity should interact with the rest of the biosphere and with each other in accordance with Darwinian principles. They reveal a middle ground between apocalypse and utopia, with two options: alter our behavior now at great expense and extend civilization or fail to act and rebuild in accordance with those same principles. If we take the latter, then our immediate goal ought to focus on preserving as many of humanity's positive achievements—from high technology to high art—as possible to shorten the time needed to rebuild.

The fundamental theory of the survival of life on this planet is Darwinism. Darwinian evolution is about coping with change by changing, using what you have on hand to survive. The fuel for this process is evolutionary potential, which resides in preexisting variation. This preexisting variation allows living systems to move forward into an uncertain future. The biosphere is a complex evolutionary system that generates, stores, and uses its own potential to survive. This makes ecosystems robust, not fragile. That suggests we can use the biosphere without destroying it, but we need some guidelines. Those guidelines are embodied in the Four Laws of Biotics, which tell us how we can interact with the biosphere without endangering ourselves further. We can further improve humanity’s chances of survival as a technological species by (1) implementing the economics of well-being, (2) reducing population density by finding space in rural areas and revitalizing them into circularized economies, (3) regrowing sustainably by creating networks of cooperating circular economies, adding new modules when growth occurs, not consolidating into new densely populated and vulnerable urban centers, and (4) modifying social institutions to be responsive to the desires of the grassroots, even when those desires do not produce the expected outcomes. Darwinian principles provide humanity with a middle ground, a third way, between unattainable utopia and unacceptable apocalypse. We can alter our behavior now according to Darwinian principles, at great expense and difficulty, and extend or even improve upon the current state of the Anthropocene, or we can fail to act on our own behalf, experience a general collapse of technological society, and rebuild using those Darwinian principles to provide a more survivable future.

BACKGROUND AND AIM: Sugarcane workers have an elevated prevalence of chronic kidney disease of non-traditional causes (CKDnt), a disease in which occupational heat exposure and intense physical exertion are suspected initiators. Sugarcane workers often first exhibit kidney dysfunction. Hyperuricemia among patients with kidney dysfunction increases risk of gout, an inflammatory condition which can result in severe pain and swelling. We previously reported that the majority of former sugarcane workers who had kidney dysfunction were experiencing hyperuricemia. We found that the use of natural remedies, including chamomile, was common in this population, though we have not yet examined whether chamomile, in particular, may influence risk of gout. Our objective was to determine if consumption of chamomile as an herbal medication was associated with lower odds of gout, among former sugarcane workers with kidney dysfunction. METHOD: The study population consisted of 311 former sugarcane workers who were patients at a renal clinic in northwestern Nicaragua. They were male, non-diabetic, attended the clinic for at least one year. Participants self-reported use of chamomile as a natural remedy in the last year. Gout in the preceding year was determined from abstracted medical records. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs), for 293 subjects with complete information on covariables age, hypertension, CKDnt stage, alcohol consumption, and allopurinol prescription. RESULTS: Gout was experienced by 26% of participants within last year. Overall, 16% percent of participants used chamomile in the last year. The adjusted odds of gout was lower among chamomile users compared with non-users, though CIs were wide (OR= 0.56, 95% CI (0.20, 1.56)). CONCLUSIONS: We cannot conclude whether chamomile use reduced odds of gout among former sugarcane workers with kidney dysfunction. However, greater understanding of what factors affect gout and hyperuricemia in this population would improve quality of life.

The Stockholm Paradigm is an evolutionary synthesis that explains the emergence of novel pathogens in the context of environmental disturbances. Considering the urgent climate change situation, anticipation stands as key to prevent and mitigate the effects that climate change can have in the emergence of pathogens. However, the success of preventive measures is hindered by a limited knowledge of the interplaying dynamics between biology, environment, and culture leading to emerging infectious diseases. For many decades, bioarcheologists have been gathering data on past human- environment interactions, therefore contributing to the conversation. Archaeoparasitology, at the intersection between pathology, bioarchaeology, and biology, is uniquely placed to enquire about the circumstances that favored the emergence of novel pathogens in the past. We illustrate this task by reviewing the existing knowledge on the evolution of Trypanosoma cruzi and emergence of Chagas disease. When the scholarship on Chagas is completed with the lessons learned from the Stockholm Paradigm, this provides a long- term perspective on environmental change and human relations leading to the emergence of an infectious disease.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies ( n = 36), health professionals ( n = 3), labor leaders ( n = 2), and family members of research participants ( n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.

The emerging infectious disease (EID) crisis represents an immediate existential threat to modern humanity. Current policies aimed at coping with the EID crisis are ineffective and unsustainably expensive. They have failed because they are based on a scientific paradigm that produced the parasite paradox. The Stockholm paradigm (SP) resolves the paradox by integrating four elements of evolutionary biology: ecological fitting, sloppy fitness space, coevolution, and responses to environmental perturbations. It explains why and how the EID crisis occurs and is expanding and what happens after an EID emerges that sets the stage for future EIDs. The SP provides a number of critical insights for changing scientific and public policy in a manner that allows us to begin coping with the EID crisis in an effective manner. It provides hope that we can anticipate EIDs and prevent them or at least mitigate their impacts. This article has been produced in support of and with appreciation for the efforts by Gábor Földvári of the Institute of Evolution, Centre for Ecological Research, and the Centre for Eco-Epidemiology, National Laboratory for Health Security (both located at 1121 Budapest, Konkoly-Thege Miklós út 29-33, Hungary). Through his untiring efforts, team building, and leadership, he has secured the first EU-wide team research grant. This work was supported by the National Research, Development and Innovation Office in Hungary (RRF-2.3.1-21-2022-00006) and the COST Action CA21170 “Prevention, anticipation and mitigation of tick-borne disease risk applying the DAMA protocol (PRAGMATICK),” which represent the first funded efforts to apply the principles of the DAMA protocol.

Climate change, emerging infectious diseases (EIDs) and food security create a dangerous nexus. Habitat interfaces, assumed to be efficient buffers, are being disrupted by human activities which in turn accelerate the movement of pathogens. EIDs threaten directly and indirectly availability and access to nutritious food, affecting global security and human health. In the next 70 years, food-secure and food-insecure countries will face EIDs driving increasingly unsustainable costs of production, predicted to exceed national and global gross domestic products. Our modern challenge is to transform this business as usual and embrace an alternative vision of the biosphere formalized in the Stockholm paradigm (SP). First, a pathogen-centric focus shifts our vision of risk space, determining how pathogens circulate in realized and potential fitness space. Risk space and pathogen exchange are always heightened at habitat interfaces. Second, apply the document-assess-monitor-act (DAMA) protocol developing strategic data for EID risk, to be translated, synthesized and broadcast as actionable information. Risk management is realized through targeted interventions focused around information exchanged among a community of scientists, policy practitioners of food and public health security and local populations. Ultimately, SP and DAMA protect human rights, supporting food security, access to nutritious food, health interventions and environmental integrity.

The COVID-19 pandemic is the latest example of the profound socioeconomic impact of the emerging infectious disease (EID) crisis. Current health security measures are based on a failed evolutionary paradigm that presumes EID is rare and cannot be predicted because emergence requires the prior evolution of novel genetic capacities for colonizing a new host. Consequently, crisis response through preparation for previously emerged diseases and palliation following outbreaks have been the only health security options, which have become unsustainably expensive and unsuccessful. The Stockholm paradigm (SP) is an alternative evolutionary framework that suggests host changes are the result of changing conditions that bring pathogens into contact with susceptible hosts, with novel genetic variants arising in the new host after infection. Host changes leading to EID can be predicted because preexisting capacities for colonizing new hosts are highly specific and phylogenetically conservative. This makes EID prevention through limiting exposure to susceptible hosts possible. The DAMA (Document, Assess, Monitor, Act) protocol is a policy extension of the SP that can both prevent and mitigate EID by enhancing traditional efforts through adding early warning signs and predicting transmission dynamics. Prevention, preparation, and palliation compose the 3P framework, a comprehensive plan for reducing the socioeconomic impact of EID.

One Health programs and trajectories are now the apparent standard for exploring the occurrence and distribution of emerging pathogens and disease. By definition, One Health has been characterized as a broadly inclusive, collaborative, and transdisciplinary approach with connectivity across local to global scales, which integrates the medical and veterinary community to recognize health outcomes emerging at the environmental nexus for people, animals, plants, and their shared landscapes. One Health has been an incomplete model, conceptually and operationally, focused on reactive and response-based foundations, to limit the impact of emerging pathogens and emerging infectious diseases and, as such, lacks a powerful proactive capacity. A proactive, predictive One Health is necessary, emanating in part from geographically/taxonomically broad and temporally deep biological collections of pathogen-host assemblages. The DAMA protocol (Document, Assess, Monitor, Act), the operational extension of the Stockholm paradigm (SP), accomplishes this task by encompassing holistic and strategic biological sampling of reservoir host assemblages and pathogens at environmental interfaces and more extensively through resurveys, with development of informatics resources digitally linked to physical specimens held in publicly accessible museum biorepositories. Archives of specimens are the foundations for accumulating interrelated archives of information (the baselines against which change can be identified and tracked), with collections serving as fundamental resources for biodiversity informatics under the conceptual evolutionary and ecological umbrella of the SP. A cultural and conceptual transformation is essential among the diverse practitioners in the One Health community, one that recognizes the necessity of placing pathogens in an evolutionary, ecological, and environmental context by integrating specimens and associated informatics into an infrastructure and networks for actionable information. As a community, it is essential to abandon response-based business as usual while looking forward toward proactive transboundary approaches that maximize our conceptual and taxonomic view of diversity across interconnected planetary scales that influence the complexity of pathogen-host interfaces. Evolution, where the past always influences the present and the future, defines our trajectory, as the need for sustained archives that describe the biosphere becomes more acute with each passing day.

The unusual genetic diversity of the Omicron strain has led to speculation about its origin. The mathematical modelling platform developed for the Stockholm Paradigm (SP) indicates strongly that it has retro-colonized humans from an unidentified nonhuman mammal, likely originally infected by humans. The relationship between Omicron and all other SARS-CoV-2 variants indicates oscillations among hosts, a core part of the SP. Such oscillations result from the emergence of novel variants following colonization of new hosts, replenishing and expanding the risk space for disease emergence. The SP predicts that pathogens colonize new hosts using pre-existing capacities. Those events are thus predictable to a certain extent. Novel variants emerge after a colonization and are not predictable. This makes it imperative to take proactive measures for anticipating emerging infectious diseases (EID) and mitigating their impact. The SP suggests a policy protocol, DAMA, to accomplish this goal. DAMA comprises: DOCUMENT to detect pathogens before they emerge in new places or colonize new hosts; ASSESS to determine risk; MONITOR to detect changes in pathogen populations that increase the risk of outbreaks and ACT to prevent outbreaks when possible and minimize their impact when they occur.

Zaćmienie darwinizmu zaczęło dobiegać końca w latach osiemdziesiątych dwudziestego wieku i obecnie proces ten znajduje się w stanie równowagi. Potrzebujemy Rozszerzonej Syntezy, przy czym termin „rozszerzona” użyty jest tutaj metaforycznie. Musimy cofnąć się w czasie, aby wydobyć ważne aspekty darwinizmu, które odstawiono na boczny tor, a później utracono w okresie panowania neodarwinizmu, i następnie wyjść poza neodarwinizm w celu ujęcia nowych danych i koncepcji. Najogólniejszy układ odniesienia Rozszerzonej Syntezy stanowi koncepcja wielkich przejść ewolucyjnych. Rozszerzona Synteza bez problemu wpisuje się w filozoficzny punkt widzenia, zgodnie z którym biologia nie musi być połączona z innymi obszarami nauki, aby znaleźć dla siebie uzasadnienie. Przekonuje mnie dawniejszy pogląd, że biologia potrzebuje nadrzędnego prawa, które połączy ją z pozostałymi obszarami nauk przyrodniczych. Karol Darwin sugerował istnienie „prawa wyższego rzędu”, ale go nie uściślił. Jeśli uda nam się zidentyfikować to prawo, to Rozszerzona Synteza stanie się Zunifikowaną Teorią Biologii, o której 25 lat temu mówili Daniel Brooks i Ed Wiley.

Cestodes of the genus Arostrilepis Mas-Coma and Tenora 1997 have a Holarctic distribution with 16 species occurring among 28 species of mostly arvicoline hosts. The type species of the genus is Arostrilepis horrida (von Linstow, 1901), described initially as Taenia horrida von Linstow, 1901, from murine rodents in Lower Saxony (Niedersachsen), Germany. Here we report the first helminth parasite from the mole-vole, Ellobius tancrei, in Mongolia which is the first subterranean rodent known to be infected with Arostrilepis in the Palearctic. In addition, we describe a new species: Arostrilepis batsaikhani n. sp. which most closely resembles A. microtis Gulyaev and Chechulin 1997, differing from this species with a genetic distance of about 4% (using cytochrome-b) and by having distinctly large cirrus spines, testes that are larger and fill the whole segment measured anterior-posterior and larger eggs.