Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Phenotype of BTK-lacking myeloid cells during prolonged COVID-19 and upon convalescent plasma.

XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.

Self-reported psychological distress and self-perceived health in residents living near pesticide-treated agricultural land: a cross-sectional study in The Netherlands.

OBJECTIVES: There is rising concern regarding possible health effects from exposure to pesticides in residents living near agricultural land. Some studies indicated increased risks of reporting symptoms of anxiety and depression among agricultural workers but less is known about the mental and perceived health of rural residents. We aimed to study possible associations between self-reported psychological distress (SPD) and self-perceived health (SPH) in residents near pesticide-treated agricultural land. METHODS: Using the Public Health Monitor national survey from 2012, we selected 216 932 participants who lived in rural and semi-urban areas of the Netherlands and changed addresses at most once in the period 2009-2012. Psychological distress (PD) was assessed via the Kessler Psychological Distress scale (K10) and participants were asked to assess their own health. We estimated the area of specific crop groups cultivated within buffers of 50 m, 100 m, 250 m and 500 m around each individual's residence for the period 2009-2012. Association between these exposure proxies and the outcomes was investigated using logistic regression, adjusting for individual, lifestyle and area-level confounders. RESULTS: Overall, results showed statistically non-significant OR across all buffer sizes for both SPD and SPH, except for the association between SPH and 'all crops' (total area of all considered crop groups) with OR (95% CI) ranging from 0.77 (0.63 to 0.93) in 50 m to 1.00 (1.00 to 1.00) in 500 m. We observed that most ORs were below unity for SPH. CONCLUSIONS: This study provides no evidence that residential proximity to pesticide treated-crops is associated with PD or poorer perceived health.

An annotated checklist of the genus Pterygodermatites Wedl, 1861 (Nematoda: Rictulariidae), with notes on hosts and geographical distribution.

Species of rictulariid nematodes belonging to the genus Pterygodermatites Wedl, 1861 are parasites of mammals with a wide geographical distribution. The taxonomy of this speciose genus is complex and based mainly on morphological traits of the cephalic structures and cuticular processes. Currently, the known species are allocated to five subgenera [P. (Paucipectines), P. (Neopaucipectines), P. (Multipectines), P. (Pterygodermatites) and P. (Mesopectines)], based on the classification proposed in 1969 by Quentin. Studies on life cycles, taxonomy, biogeography and association of these parasites with mammals peaked at the end of the 1960s. Although the momentum was lost, new species and geographic records have been added in the last 50 years. Therefore, an updated checklist of species of Pterygodermatites is presented here, based on a literature survey. Information on classification, geographical distribution and host range obtained for 68 species is presented, including a distribution map. Moreover, the main differential morphological traits related to each species are tabulated. More than 140 species from 10 different mammalian orders (Carnivora, Chiroptera, Didelphimorphia, Erinaceomorpha, Macroscelidae, Microbiotheria, Paucituberculata, Primates, Rodentia and Xenarthra) have been reported as hosts of Pterygodermatites spp. The taxonomic information here compiled can contribute to future studies on the biogeography, in addition to evolutionary and ecological aspects of this diverse but poorly known genus of parasitic nematodes of mammals.

Precarious working conditions and health of metropolitan bus drivers and conductors in Minas Gerais, Brazil.

BACKGROUND: To investigate the relationship between precarious working conditions and the health of bus drivers and conductors. METHODS: Data were gathered by means of a survey and interviews conducted in 2012 with 1607 employees of the public transport system of the metropolitan region of Belo Horizonte, Brazil. Nine proxy variables were used to create a precariousness score, ranging from 0 to 9, on a comparative scale: score 0 "less precarious" and 9 "more precarious." Negative self-evaluations of health, medical diagnoses of depression and sleep disorders, common mental disorders, musculoskeletal pain and medical leave were assessed. Poisson regression was used to assess associations between precariousness and health adjusted for age, sex, education, vibration, and noise. RESULTS: The sample was composed of 853 drivers and 754 conductors. Most were men (87%), with age below 40 years (67.4%) and medium educational level (64.5%). The maximum precariousness score observed was 7. Most individuals were in the groups of scores 3 (26.7%) and 4 (26.1%). The prevalences of the health situations were: common mental disorders, 26.3%; medical diagnosis of depression, 9.7%; medical diagnosis of sleep disorder, 14.6%; musculoskeletal pain, 43.0%; medical leave (absenteeism), 34.8%; and negative self-evaluation of health, 20.2%. The prevalences of health conditions, with the exception of negative self-evaluations of health, were significantly higher among workers with higher levels of precarious working conditions. CONCLUSIONS: Worse health, particularly common mental disorders, was associated with self-assessed work precariousness.

Surveillance perspective on Lyme borreliosis across the European Union and European Economic Area.

Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe. Erythema migrans (EM), an early, localised skin rash, is its most common presentation. Dissemination of the bacteria can lead to more severe manifestations including skin, neurological, cardiac, musculoskeletal and ocular manifestations. Comparison of LB incidence rates in the European Union (EU)/European Economic Area (EEA) and Balkan countries are difficult in the absence of standardised surveillance and reporting procedures. We explored six surveillance scenarios for LB surveillance in the EU/EEA, based on the following key indicators: (i) erythema migrans, (ii) neuroborreliosis, (iii) all human LB manifestations, (iv) seroprevalence, (v) tick bites, and (vi) infected ticks and reservoir hosts. In our opinion, neuroborreliosis seems most feasible and useful as the standard key indicator, being one of the most frequent severe LB manifestations, with the possibility of a specific case definition. Additional surveillance with erythema migrans as key indicator would add value to the surveillance of neuroborreliosis and lead to a more complete picture of LB epidemiology in the EU/EEA. The other scenarios have less value as a basis for EU-level surveillance, but can be considered periodically and locally, as they could supply complementary insights.

Denervation impairs regeneration of amputated zebrafish fins.

BACKGROUND: Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear. RESULTS: We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration. CONCLUSIONS: Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.

Differentiated skeletal cells contribute to blastema formation during zebrafish fin regeneration.

The origin of cells that generate the blastema following appendage amputation has been a long-standing question in epimorphic regeneration studies. The blastema is thought to originate from either stem (or progenitor) cells or differentiated cells of various tissues that undergo dedifferentiation. Here, we investigate the origin of cells that contribute to the regeneration of zebrafish caudal fin skeletal elements. We provide evidence that the process of lepidotrichia (bony rays) regeneration is initiated as early as 24 hours post-amputation and that differentiated scleroblasts acquire a proliferative state, detach from the lepidotrichia surface, migrate distally, integrate into the blastema and dedifferentiate. These findings provide novel insights into the origin of cells in epimorphic appendage regeneration in zebrafish and suggest conservation of regeneration mechanisms between fish and amphibians.

Left atrial appendage occlusion for recurrent stroke while on oral anticoagulation: a case series.

Background: Clinical practice guidelines recommend oral anticoagulation (OAC) for stroke prevention in selected patients with atrial fibrillation (AF). However, some patients still experience thrombo-embolic events despite adequate anticoagulation. The optimal management of these cases remains uncertain, leading to practice pattern variability. We present a series of three cases illustrating the use of left atrial appendage occlusion (LAAO) as an adjunctive stroke prevention strategy in AF patients with recurrent thrombo-embolic events despite adequate anticoagulation. Case summary: Case one describes an 89-year-old female on apixaban who presented with a thrombus and underwent successful mechanical thrombectomy. Left atrial appendage occlusion was performed, and no subsequent thrombo-embolic events were reported. Case 2 involves a 72-year-old female on full-dose apixaban who experienced recurrent strokes despite adequate anticoagulation. Thrombectomy was performed twice, and complications arose during LAAO. The patient was discharged on warfarin + clopidogrel and remained event-free at the six-month follow-up. Case 3 features an 88-year-old female on rivaroxaban who experienced recurrent cerebral ischaemic events and gastrointestinal bleeding. Left atrial appendage occlusion using an Amplatzer Amulet™ device was successful, and the patient remained event-free at the one-year follow-up. Discussion: This case series emphasizes the complexity of stroke prevention in AF patients and underscores the need for an individualized approach. Incorporating LAAO alongside OAC can provide additional stroke protection for patients with inadequate response to anticoagulation. Further randomized controlled trials are needed to evaluate the efficacy and safety of this approach. In light of the limited evidence available, these cases contribute to the growing body of knowledge on the potential role of LAAO in secondary stroke prevention in AF patients with recurrent thrombo-embolic events despite appropriate anticoagulation.

Unstable Angina Risk Stratification Using High-Sensitivity Cardiac Troponin and Coronary Angiography.

Patients formerly diagnosed with unstable angina (UA) are being reclassified as non-ST-elevation myocardial infarction with the widespread adoption of high-sensitivity troponin (hsTn) assays, leading to significant changes in the incidence and prognosis of UA. This study aimed to evaluate the value of hsTn and the presence of significant obstructive coronary artery disease (CAD) in the risk stratification of patients with UA. We conducted a retrospective, single-center study of 742 patients hospitalized for UA between 2016 and 2021. The primary end point of this study was all-cause mortality. The secondary outcome (major adverse cardiac events [MACEs]) was defined as a composite of nonfatal myocardial infarction (MI), hospitalization for heart failure (hHF), and repeated coronary angiography because of recurring UA (rUA) after the index event. The outcomes were assessed within 1 month, 1 year, and up to 5 years of follow-up. The average follow-up duration was 45 ± 24 months, and 37.2% (n = 276) of patients completed a 5-year follow-up. No in-hospital death was observed, and 6.9% of patients died during follow-up, which was more commonly a late event (>12 months). The composite secondary end point (MI+hHF+rUA) was observed in 16.7% of the patients. There were 3.2% nonfatal MI, 2.3% hHF, and 11.6% rUA during follow-up. We developed a risk model (UA mortality risk) using variables with the highest discriminatory power: age, hsTn, and ST-segment deviation. Our model performed well against the Global Registry of Acute Coronary Events and Thrombolysis in Myocardial Infarction risk scores in predicting death during follow-up. Obstructive CAD on coronary angiography was the only independent predictor of MACEs during follow-up. In conclusion, a contemporary cohort of patients with UA presented with favorable prognosis, particularly, within the first year after the index event. Nonsignificant increases in hsTn levels add to the risk stratification of patients with UA, and the presence of obstructive CAD was the only independent predictor of MACEs, highlighting the potential importance of assessing coronary anatomy.

Outdoor air pollution as a risk factor for testing positive for SARS-CoV-2: A nationwide test-negative case-control study in the Netherlands.

Air pollution is a known risk factor for several diseases, but the extent to which it influences COVID-19 compared to other respiratory diseases remains unclear. We performed a test-negative case-control study among people with COVID-19-compatible symptoms who were tested for SARS-CoV-2 infection, to assess whether their long- and short-term exposure to ambient air pollution (AAP) was associated with testing positive (vs. negative) for SARS-CoV-2. We used individual-level data for all adult residents in the Netherlands who were tested for SARS-CoV-2 between June and November 2020, when only symptomatic people were tested, and modeled ambient concentrations of PM10, PM2.5, NO2 and O3 at geocoded residential addresses. In long-term exposure analysis, we selected individuals who did not change residential address in 2017-2019 (1.7 million tests) and considered the average concentrations of PM10, PM2.5 and NO2 in that period, and different sources of PM (industry, livestock, other agricultural activities, road traffic, other Dutch sources, foreign sources). In short-term exposure analysis, individuals not changing residential address in the two weeks before testing day (2.7 million tests) were included in the analyses, thus considering 1- and 2-week average concentrations of PM10, PM2.5, NO2 and O3 before testing day as exposure. Mixed-effects logistic regression analysis with adjustment for several confounders, including municipality and testing week to account for spatiotemporal variation in viral circulation, was used. Overall, there was no statistically significant effect of long-term exposure to the studied pollutants on the odds of testing positive vs. negative for SARS-CoV-2. However, significant positive associations of long-term exposure to PM10 and PM2.5 from specifically foreign and livestock sources, and to PM10 from other agricultural sources, were observed. Short-term exposure to PM10 (adjusting for NO2) and PM2.5 were also positively associated with increased odds of testing positive for SARS-CoV-2. While these exposures seemed to increase COVID-19 risk relative to other respiratory diseases, the underlying biological mechanisms remain unclear. This study reinforces the need to continue to strive for better air quality to support public health.

Exploring associations between residential exposure to pesticides and birth outcomes using the Dutch birth registry.

BACKGROUND: Maternal occupational exposure to pesticides has been linked to adverse birth outcomes but associations with residential pesticide exposures are inconclusive. OBJECTIVES: To explore associations between residential exposure to specific pesticides and birth outcomes using individual level exposure and pregnancy/birth data. METHODS: From all 2009-2013 singleton births in the Dutch birth registry, we selected mothers > 16 years old living in non-urban areas, who had complete address history and changed addresses at most once during pregnancy (N = 339,947). We estimated amount (kg) of 139 active ingredients (AI) used within buffers of 50, 100, 250 and 500 m around each mother's home during pregnancy. We used generalized linear models to investigate associations between 12 AIs with evidence of reproductive toxicity and gestational age (GA), birth weight (BW), perinatal mortality, child́s sex, prematurity, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA), adjusting for individual and area-level confounders. For the remainder 127 AIs, we used minimax concave penalty with a stability selection step to identify those that could be related to birth outcomes. RESULTS: Regression analyses showed that maternal residential exposure to fluroxypyr-meptyl was associated with longer GA, glufosinate-ammonium with higher risk of LBW, linuron with higher BW and higher odds of LGA, thiacloprid with lower odds of perinatal mortality and vinclozolin with longer GA. Variable selection analysis revealed that picoxystrobin was associated with higher odds of LGA. We found no evidence of associations with other AIs. Sensitivity and additional analysis supported these results except for thiacloprid. DISCUSSION: In this exploratory study, pregnant women residing near crops where fluroxypyr-meptyl, glufosinate-ammonium, linuron, vinclozolin and picoxystrobin were applied had higher risk for certain potentially adverse birth outcomes. Our findings provide leads for confirmatory investigations on these compounds and/or compounds with similar modes of action.

Suppressing glucose transporter gene expression in schistosomes impairs parasite feeding and decreases survival in the mammalian host.

Adult schistosomes live in the host's bloodstream where they import nutrients such as glucose across their body surface (the tegument). The parasite tegument is an unusual structure since it is enclosed not by the typical one but by two closely apposed lipid bilayers. Within the tegument two glucose importing proteins have been identified; these are schistosome glucose transporter (SGTP) 1 and 4. SGTP4 is present in the host interactive, apical tegumental membranes, while SGTP1 is found in the tegumental basal membrane (as well as in internal tissues). The SGTPs act by facilitated diffusion. To examine the importance of these proteins for the parasites, RNAi was employed to knock down expression of both SGTP genes in the schistosomula and adult worm life stages. Both qRT-PCR and western blotting analysis confirmed successful gene suppression. It was found that SGTP1 or SGTP4-suppressed parasites exhibit an impaired ability to import glucose compared to control worms. In addition, parasites with both SGTP1 and SGTP4 simultaneously suppressed showed a further reduction in capacity to import glucose compared to parasites with a single suppressed SGTP gene. Despite this debility, all suppressed parasites exhibited no phenotypic distinction compared to controls when cultured in rich medium. Following prolonged incubation in glucose-depleted medium however, significantly fewer SGTP-suppressed parasites survived. Finally, SGTP-suppressed parasites showed decreased viability in vivo following infection of experimental animals. These findings provide direct evidence for the importance of SGTP1 and SGTP4 for schistosomes in importing exogenous glucose and show that these proteins are important for normal parasite development in the mammalian host.

Fetomaternal hemorrhage: a clue to intraplacental choriocarcinoma and neonatal malignancy.

Fetomaternal hemorrhage (FMH) is a known cause of neonatal anemia due to fetal blood loss to the maternal circulation, occurring when the maternal-fetal barrier is disrupted. Several causes must be considered, although in most cases the etiology remains unknown. Intraplacental choriocarcinoma (ICC) is a rare entity and has been related with massive FMH, intrauterine fetal demise, severe neonatal anemia and metastatic choriocarcinoma in both mother and infant. There are 25 cases of histopathologically confirmed ICC complicated with FMH described in the literature. Because FMH occurs unexpectedly and the majority of patients with ICC are asymptomatic, this diagnosis may be missed. Once FMH is confirmed, underlying malignancy should be kept in mind. The authors present a case report of severe neonatal anemia following FMH related to ICC and highlight the importance of serum ß-hCG monitoring in cases of massive FMH.

Neurosyphilis: The Great Imitator.

Syphilis is a sexually transmitted disease caused by spirochete Treponema pallidum, with a growing incidence documented in recent years. Its clinical course is divided into three phases - primary, secondary, and tertiary syphilis - and virtually any organ can be affected, resulting in diverse clinical manifestations, making the diagnosis challenging. Neurosyphilis is a progressive, destructive disease of the central nervous system (CNS) that can develop at any stage of the infection, leading to meningeal involvement, meningovascular disease, or parenchymal syphilis (including tabes dorsalis and general paresis). Its clinical manifestations are heterogeneous and vary from focal neurologic signs to neuropsychiatric manifestations. The diagnosis is based mainly on the clinical picture and study of cerebrospinal fluid. Neuroimaging is helpful and sometimes essential, with magnetic resonance imaging being the most sensitive radiologic method, although there are no pathognomonic radiologic signs. Treatment of all forms of neurosyphilis is based on parenteral penicillin. We present a case of neurosyphilis in a patient presenting with a subacute confusional state and initial imaging findings suggestive of metastatic CNS lesions.

Residential proximity to crops and agricultural pesticide use and cause-specific mortality: A prospective census-based cohort study in the Netherlands.

BACKGROUND: There is continued concern about residential proximity to agricultural pesticide use and possible adverse health effects. Studies on this subject have been scarce with inconsistent results. We explored associations between residential proximity to specific crops, pesticide use and cause-specific mortality in a prospective census-based cohort study in The Netherlands. METHODS: Selecting inhabitants aged >30 living in less urbanized areas, at the same address for nine years up to baseline (2004) from a national register-based cohort, we followed ~3.1 million individuals for cause-specific mortality until 2012. We estimated the area of specific crop groups cultivated within buffers of 50 m, 100 m and 250 m around each individual's residence and the amount of fungicides, herbicides and insecticides used within the same buffers for the period 1995-2003. The association between these exposure proxies and 25 primary causes of death was investigated using Cox proportional hazards regression, adjusting for individual and area-level confounders. RESULTS: Residential proximity to crops was associated with decreased mortality risks overall. In contrast to the overall trend an increased risk was observed for chronic lower respiratory diseases and proximity to maize cultivation. We found no evidence of an association between the amount of pesticides used and cause-specific mortality. CONCLUSIONS: In a large prospective census-based cohort study in The Netherlands we found evidence of an increased risk of chronic lower respiratory diseases in relation to maize cultivation which was not reflected in general pesticide use, hinting to specific pesticides or practices in maize cultivation that may lead to the observed increased risk.

Residential proximity to livestock animals and mortality from respiratory diseases in The Netherlands: A prospective census-based cohort study.

BACKGROUND: There is increasing evidence of associations between residential proximity to livestock farms and respiratory morbidity, but less is known about potential effects on respiratory mortality among residents. OBJECTIVES: We aimed to assess potential associations between respiratory mortality and residential proximity to (intensive) livestock farming. METHODS: In DUELS, a national census-based cohort, we selected all inhabitants from rural and semi-urban areas of the Netherlands, aged ≥30 years and living at the same address for five years up to baseline (2004). We followed these ∼4 million individuals for respiratory mortality (respiratory system diseases, chronic lower respiratory diseases, pneumonia) from 2005 to 2012. We computed the average number of cattle, pigs, chicken, and mink present in 500 m, 1000 m, 1500 m and 2000 m of each individual's residence in the period 1999-2003. Analyses were conducted using Cox proportional hazards regression, adjusting for potential confounders at individual and neighbourhood level. RESULTS: We found evidence that living up to 2000 m of pig farms was associated with respiratory mortality, namely from chronic lower respiratory diseases, with Hazard Ratios ranging from 1.06 (1.02, 1.10) in people living close to low numbers (

Progressive Multifocal Leukoencephalopathy in a Chemotherapy-Naive Patient With Chronic Lymphocytic Leukemia: A Case Report.

Progressive multifocal leukoencephalopathy is a rare, progressive demyelinating disease of the central nervous system caused by reactivation and replication of the John Cunningham (JC) virus in cerebral oligodendrocytes. The JC virus is a small ubiquitous polyomavirus that can be detected in up to 50% of the adult population. It affects almost exclusively immunocompromised patients and is generally observed in patients with acquired immunodeficiency syndrome and patients with hematologic malignancies and autoimmune or chronic inflammatory diseases medicated with immunosuppressive and immunomodulatory drugs. However, it is rarely described in patients with hematologic malignancies, not undergoing chemotherapy or immunosuppressive therapy. It has a poor prognosis, and the treatment is based on restoring the immune system, given that no specific antiviral treatment is available. We present a case of a chemotherapy-naive patient with chronic lymphocytic leukemia associated with progressive multifocal leukoencephalopathy.

Size does not matter: molecular phylogeny reveals one of the largest trematodes from vertebrates, the enigmatic Ithyoclinostomum dimorphum, as a species of Clinostomum (Trematoda: Clinostomidae).

Despite the recent advances raised in the molecular era to the taxonomic knowledge of species of the family Clinostomidae, especially those belonging to the specious genus Clinostomum, some groups of these vertebrate parasites remain poorly studied. This is the case of species of the enigmatic genus Ithyoclinostomum Witenberg, 1926, until recently monotypic and restricted to South America, but with its occurrence expanded to North America after the description of I. yamagutii Rosser et al., 2020. Nevertheless, molecular data for the type species of the genus, Ithyoclinostomum dimorphum (Diesing, 1850), is lacking so far. In the present study, large clinostomid metacercariae morphologically indistinguishable from I. dimorphum were obtained from two erythrinid fishes from the Rio Doce River, Southeast Brazil. Samples of the parasites were subjected to a multigene (28S rDNA, ITS and cox1) molecular characterization followed by phylogenetic reconstructions. Phylogenies based on single-gene and concatenated datasets revealed unequivocally that I. dimorphum falls in a well-supported clade together with species of the genus Clinostomum. Moreover, the molecular divergences observed in relation to Clinostomum spp. [ranges of 2.4-6%, 2.4-3.8% and 14.7-19.3% for the ITS, 28S and cox1 genes, respectively] are compatible with a congeneric status with these species. Therefore, the genus Ithyoclinostomum is here synonymized with Clinostomum Leidy, 1856 and C. dimorphum (Diesing, 1850) Braun, 1899 re-established. In the phylogenetic analysis, the recently described 'Ithyoclinostomum' yamagutii, presented as an isolated, independent lineage, showing significant molecular divergences to C. dimorphum (12.6%, 7.6%, 18,6% for the ITS, 28S and cox1 genes, respectively). However, given the complex scenario raised in the morphology-based taxonomy of Clinostomidae, we took a conservative approach by not proposing a new genus to 'I.' yamagutii until molecular data of other clinostomid genus from birds, Clinostomatopsis, become available. Data here presented reveals that body size is not a useful criterion for higher-level classification in Clinostomidae. Finally, we highlighted the importance of the availability of molecular data for the type species of trematode genera proposed from South America to support a trans- or intercontinental distribution.

Origin and function of activated fibroblast states during zebrafish heart regeneration.

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.