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Abstract Background Echinococcus granulosus and E. multilocularis are tapeworm parasites of major medical and veterinary importance, causing cystic and alveolar echinococcosis, respectively. Both diseases are listed among the most severe parasitic diseases in humans, representing 2 of the 17 neglected diseases prioritised by the World Health Organisation. However, little is known about the role of urban animals in transmission of both parasite species. Findings A sensitive non-invasive genetic method was used to monitor E. granulosus and E. multilocularis infection among dog faecal samples collected from an urban area in Estonia in 2012–13. Out of 181 dog faecal samples analysed, 2.2% tested positive for E. granulosus, determined by sequencing as genotype G1. None of the samples tested positive for E. multilocularis. Conclusions We report contamination of an urban environment with highly pathogenic E. granulosus G1 disseminated by dogs, and a potential risk to human health.

Background: Undifferentiated acute febrile illness (UAFI) cause by several pathogens poses a diagnostic challenge due to the similarity on the clinical manifestations across these diseases. Precise pathogen detection is vital for appropriate medical intervention, early treatment, and timely outbreak alerts regarding emerging pathogens. In tropical regions, UAFI is predominantly linked to a wide range of viral, bacterial, and parasitic infections. Hence, confirmatory laboratory tests are essential for specific pathogen identification., Objectives: Our primary goal was to develop two real-time multiplex polymerase chain reaction (PCR) assays for simultaneous detection of six neglected pathogens (Leptospira spp., Rickettsia spp., Borrelia spp., Anaplasma spp., Brucella spp., and Bartonella spp.), known for causing UAFI in tropical regions., Methods: We rigorously assessed assays parameters including: linearity, efficiency, sensitivity, and reproducibility in both singleplex and multiplex formats., Findings: Our results demonstrated that these multiplex assays are reliable and sensitive methods. They showed good performance with low intra- and inter-variability (< 10%) and consistently high efficiencies (> 90%)., Main Conclusions: These assays offer the alternative of streamlining work, reducing processing costs, and minimizing sample volume use. In conclusion, we present two dependable, user-friendly, rapid, and cost-effective methods for simultaneously detecting six neglected bacteria, as a significant laboratory tool in resource-limited tropical settings.

Phlebotomine sand flies are critical vectors of Leishmania parasites, impacting public health significantly. This study focused on assessing the diversity of sand flies in a rural area of El Carmen de Bolívar Municipality, northern Colombia, employing rarefaction curves and Hill numbers to understand potential vector communities and inform environmental management. From January 2018 to April 2019 (five samplings), sand flies were collected using CDC light traps with blue LED in domestic/peridomestic/sylvatic ecotopes, identifying species per Young and Duncan (1994) and Galati (2003). Hill numbers provided diversity estimates across samples, while Principal Component Analysis correlated with environmental factors with phlebotomine species presence and abundance. 8,784 phlebotomine individuals were collected; 56.4 % females and 43.6% males (ratio 3:2). These individuals belonged to eight species: Pintomyia evansi, Psychodopygus panamensis, Lutzomyia gomezi, Micropygomyia cayennensis, Evandromyia dubitans, Psathyromyia aclydifera, Pintomyia serrana, and Pintomyia rangeliana; with Pi. evansi being the most abundant species (74.39 %; 6,530 exemplars). The ANOVA showed no significant differences between phlebotomine sand flies abundances across ecotopes (p = 0.018). Species of epidemiological relevance as Pi. evansi and Lu. gomezi not show a positive correlation with environmental variables evaluated, only Ps. panamensis was positively correlated with precipitation. However, the study emphasizes the need for a continuous sand fly monitoring and research to enhance leishmaniasis control strategies, highlighting the necessity to expand knowledge on phlebotomine diversity and environmental interactions to understand vector ecology and disease dynamics better., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Motivation for the study. The role of bats as hosts of Trypanosoma spp. in the Atlantic department in Colombia, as well as its taxonomic diversity has been poorly studied. Main findings. This is the first report of frequency of infection by Trypanosoma spp. in bats in the Atlántico Department in Colombia. Implications. The great adaptive capacity of bats to different ecological niches and its role as hosts of Trypanosoma spp. for wild and urban ecotopes represents a risk factor in transmission cycles of epidemiological importance. We conducted a study to evaluate the frequency of infection by Trypanosoma spp. in bats captured in wild and urban ecotopes in the Department of Atlántico in the Caribbean region of Colombia from March 2021 to May 2022. Bats were taxonomically identified, and sex, relative age, and reproductive conditions were determined. A blood sample was used for parasitological analysis and DNA extraction to amplify a region of the 18S rRNA. 125 bats were collected, with the most abundant families being Molossidae (62/125; 49.6%) and Phyllostomidae (43/125; 34.4%). Molossus molossus collected in wild habitats showed an infection frequency of 8.1% (5/61) and 4.1% (3/61) through parasitological and molecular analysis, respectively. In comparison, Noctilio albiventris collected in urban habitats showed an infection frequency of 16.6% (2/12) for both analyses. These findings represent the first records of M. molossus harboring trypanosomes for the Department of Atlántico and of N. albiventris harboring trypanosomes in Colombia.

In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management., Competing Interests: Eguzki&ntilde;e Diez-Martin, Leidi Hernandez-Suarez, Egoitz Astigarraga, and Gabriel Barreda-G&oacute;mez were employed by IMG Pharma Biotech S.L. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction. El Alférez, a village in Los Montes de María (Bolívar, Colombia) and a macro-focus of leishmaniasis, recorded its first case in 2018, evidencing changes in the distribution and eco-epidemiology of the disease, although interactions between vectors and local fauna remain unknown. Objective. To evaluate the diversity of sandflies and their blood meal sources in the community of El Alférez in the municipality of El Carmen de Bolívar (Bolívar, Colombia). Materials and methods. In 2018, sandflies were collected using LED-based light traps in domestic, peridomestic, and sylvatic ecotopes and identified at the species level. Multiplex polymerase chain reaction targeting the mitochondrial cytochrome B gene was used to analyze blood from the digestive tract. Results. Lutzomyia evansi was the most abundant species (71.85%; n = 485/675), followed by Lu. panamensis, Lu. gomezi, Lu. trinidadensis, Lu. dubitans, Lu. abonnenci, and Lu.aclydifera. Twenty-five percent of the species had blood meals from Canis familiaris (36.00%; n = 9/25), Ovis aries (36.00%; n=9:/25), Bos taurus (24.00%; n = 6/25), Sus scrofa (20.00%; n = 5/25), and Homo sapiens (8.00%; n = 2/25). Lutzomyia evansi registered the highest feeding frequency (68.00%; n = 17/25), predominantly on a single (44.00%; n = 11/25) or multiple species (24.00%; n = 6/25). Conclusion. Results indicate a eclectic feeding behavior in Lu. evansi, implying potential reservoir hosts for Leishmania spp. and increasing transmission risk. This study is a first step towards understanding the diversity of mammalian blood sources used by sandflies, that may be crucial for vector identification and formulation of effective control measures.

Purpose: Trypanosoma cruzi and Leishmania spp. coexist in several endemic areas, and there are few studies of Chagas disease and leishmaniasis coinfection worldwide; for this reason, the objective of this work was to determine the Chagas disease and leishmaniasis coinfection in several rural communities co-endemic for these diseases., Methods: A total of 1107 human samples from six co-endemic rural communities of Cojedes state, Venezuela, were analyzed. Serum samples were evaluated by ELISA, indirect hemagglutination, and indirect immunofluorescence for Chagas disease diagnosis, and individuals were evaluated for leishmaniasis by leishmanin skin test (LST). Approximately, 30% of the individuals were also analyzed by PCR (blood clot samples) for T. cruzi and for Leishmania spp., Results: The 14.7% of the individuals were positive to Trypanosoma cruzi infection by serology, and 25.8% were positive to Leishmania spp. current or past infection by LST. Among the group with PCR results, 7.8% were positive for T. cruzi, and 9.4% for Leishmania spp. The coinfection T. cruzi/Leishmania spp. was 6.5%. The T. cruzi DTUs of the positive blood clot samples were TcI, revealed using the molecular markers: (i) intergenic region of the miniexon, (ii) D7 divergent domain of the 24Sα rDNA, (iii) size-variable domain of the 18S rDNA, and (iv) hsp60-PCR-RFLP (EcoRV). The Leishmania species identified were L. (Leishmania) mexicana and L. (Viannia) braziliensis., Conclusion: A high prevalence was found for T. cruzi and Leishmania spp. single and coinfections in almost all communities studied, being these results of relevance for the implementation of control programs in co-endemic areas., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance.

Tritrichomonas foetus is a protozoan parasite that causes a venereal disease in cattle limiting reproduction by abortions and sterility. The immune response against this parasite is poorly understood. Since the iron and calcium ions are important regulators of the microenvironment of the urogenital tract in cattle, we decided to evaluate the role of these divalent cations on the antigenicity of membrane proteins of T. foetus on macrophage activation as one of the first inflammatory responses towards this pathogen. Colorimetric methods and ELISA were used to detect the nitric oxide and oxygen peroxide production and expression of cytokines in culture supernatant from macrophage incubated with membrane proteins from T. foetus cultured in iron- and calcium-rich conditions. qRT-PCR assays were used to evaluate the transcript expression of genes involved in the inflammatory response on the macrophages. The membrane proteins used for in vitro stimulation caused the up-regulation of the iNOS and NOX-2 genes as well as the generation of NO and H 2 O 2 in murine macrophages on a dependent way of the metal concentrations. Additionally, after stimulation, macrophages showed a considerable rise in pro-inflammatory cytokines and a downregulation of anti-inflammatory cytokines, as well as up-regulation in the transcription of the TLR4 and MyD88 genes. These data suggest that membrane proteins of T. foetus induced by iron and calcium can activate an inflammatory specific macrophage response via TLR4/MyD88 signalling pathway., (© 2024 John Wiley & Sons Ltd.)

It is estimated that 6-7 million people worldwide are infected with Trypanosoma cruzi, the parasite that causes Chagas disease. In Venezuela, Chagas disease remains a public health problem. In this work, T. cruzi isolates from six species of triatomines and mammals of the orders Didelphimorphia and Xenarthra, captured in rural communities of Monagas, underwent parasitological and molecular characterization. A total of 471 triatomines and 17 mammals were captured, with a natural infection rate of 41.4% and 70.6%, respectively. In the male NMRI mouse model used for parasitological characterization (prepatent period, parasitemia curve, mouse mortality, and tissular parasitism), T. cruzi isolates exhibited high lethality due to their pronounced virulence, irrespective of the parasite load in each mouse, resulting in a mortality rate of 75%. Among the vector isolates, in the mouse model, only 2 out of 6 remained alive, while the rest perished during the evaluation. Conversely, the isolates from mammals proved fatal for all the inoculated mice. All isolates were identified as belonging to DTU TcI, based on the molecular markers such as the intergenic region of the miniexon, D7 divergent domain of the 24Sα rDNA, size-variable domain of the 18S rDNA, and hsp60-PCR-RFLP-EcoRV. This study demonstrates the presence of vectors and mammalian reservoirs naturally infected with T. cruzi in communities of Monagas, the 9th largest and 9th most populous state in Venezuela. This situation represents a neglected epidemiological problem demanding urgent attention and imperative health care intervention., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study was conducted to dissect the role and potential mechanism of microRNA (miR)-455-3p on osteosarcoma (OS) development., Methods: miR-455-3p and HSF1 expression in OS tissues were detected by RT-qPCR and western blot. Later, gain- and loss-of-function assays were implemented in OS cells U-2OS and MNNG. The expression of apoptosis-related genes was measured by RT-qPCR and western blot. MTT, Transwell, scratch test, and flow cytometry were utilized to test OS cell viability, invasion, migration, and apoptosis. The targeting relationship between miR-455-3p and HSF1 was assessed with a dual-luciferase reporter gene assay. The transplantation tumor experiment in nude mice was utilized for in vivo confirmation., Results: Downregulated miR-455-3p and upregulated HSF1 were displayed in OS tissues and cells. Mechanistically, miR-455-3p negatively targeted HSF1. MiR-455-3p inhibition or HSF1 overexpression increased MNNG and U-2OS cell proliferative, invasive, and migrating capabilities, while diminishing U-2OS cell apoptosis. Moreover, HSF1 overexpression negated the impacts of miR-455-3p upregulation on OS cell proliferative, invasive, migrating, and apoptotic abilities. Likewise, overexpressing miR-455-3p curtailed the growth of transplanted OS tumors through HSF1 repression., Conclusion: MiR-455-3p inhibits the development of OS cells by downregulating HSF1, highlighting the possibility of miR-455-3p as an innovative indicator of prognosis and a therapeutic target for OS., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The proliferation of the e-commerce market has posed challenges to staff safety, product quality, and operational efficiency, especially for cold chain logistics (CCL). Recently, the logistics of vaccine supply under the worldwide COVID-19 pandemic rearouses public attention and calls for innovative solutions to tackle the challenges remaining in CCL. Accordingly, this study proposes a cyber-physical platform framework applying the Internet of Everything (IoE) and Digital Twin (DT) technologies to promote information integration and provide smart services for different stakeholders in the CCL. In the platform, reams of data are generated, gathered, and leveraged to interconnect and digitalize physical things, people, and processes in cyberspace, paving the way for digital servitization. Deep learning techniques are used for accident identification and indoor localization based on Bluetooth Low Energy (BLE) to actualize real-time staff safety supervision in the cold warehouse. Both algorithms are designed to take advantage of the IoE infrastructure to achieve online self-adapting in response to surrounding evolutions. Besides, with the help of mobile and desktop applications, paperless operation for shipment, remote temperature and humidity (T&H) monitoring, anomaly detection and warning, and customer interaction are enabled. Thus, information traceability and visibility are highly fortified in this way. Finally, a real-life case study is conducted in a pharmaceutical distribution center to demonstrate the feasibility and practicality of the proposed platform and methods. The dedicated hardware and software are developed and deployed on site. As a result, the effectiveness of staff safety management, operational informatization, product quality assurance, and stakeholder loyalty maintenance shows a noticeable improvement. The insights and lessons harvested in this study may spark new ideas for researchers and inspire practitioners to meet similar needs in the industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier Inc. All rights reserved.)

Panstrongylus is a Neotropical taxa of 16 species, some more widespread than others, that act as vectors of Trypanosoma cruzi , the etiologic agent of Chagas disease (CD). This group is associated with mammalian reservoir niches. There are few studies of the biogeography and niche suitability of these triatomines. Using zoo-epidemiological occurrence databases, the distribution of Panstrongylus was determined based on bioclimatic modelling (DIVA GIS), parsimonious niche distribution (MAXENT), and parsimony analysis of endemic species (PAE). Through 517 records, a wide presence of P. geniculatus , P. rufotuberculatus , P. lignarius , and P. megistus was determined and recorded as frequent vectors of T. cruzi in rainforest habitats of 24-30 °C. These distributions were modeled with AUC >0.80 and <0.90, as well as with the seasonality of temperature, isothermality, and precipitation as relevant bioclimatic variables. Individual traces for each taxon in Panstrongylus -1036 records-showed widely dispersed lines for frequent vectors P. geniculatus , P. lignarius , P. rufotuberculatus , and P. megistus . Other occasional vectors showed more restricted dispersal, such as P. howardi , P. humeralis , P. lenti , P. lutzi , P. tupynambai , P. noireaiui , and P. chinai . Areas of defined environmental variation, geological change, and trans domain fluid fauna, such as the American Transition Zone and the Pacific Domain of Morrone, had the highest Panstrongylus diversity. Pan-biogeographic nodes appear to be areas of the greatest species diversity that act as corridors connecting biotopes and allowing fauna migration. Vicariance events in the geologic history of the continent need to be investigated. The geographical distribution of Panstrongylus overlapped with CD cases and Didelphis marsupialis/Dasypus novemcinctus presence, two important reservoirs in Central and South America. The information derived from the distribution of Panstrongylus provides knowledge for surveillance and vector control programs. It would increase information on the most and less relevant vector species of this zoonotic agent, for monitoring their population behavior.

Background: Severe acute respiratory syndrome coronavirus 2 continues to threaten public health. The virus is causing breakthrough infections in vaccinated individuals. Also, scarce information is available about cutaneous manifestations after severe acute respiratory syndrome coronavirus 2 infection., Case Presentation and Findings: A case of a triple-vaccinated (Pfizer) 37-year-old Hispanic American (Colombian) male who developed urticaria after Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 breakthrough infection is described. Virus isolation and whole genome sequencing along with immune and molecular assays were performed. Dermatological manifestations (skin rash and urticaria) after Omicron BA.5.1 infection were observed. Sequence analysis of the Omicron BA.5.1 isolate also revealed several important mutations. Hemogram analysis revealed leukocytosis and neutrophilia. Serology testing revealed anti-spike immunoglobulin G serum titers but negative detection of immunoglobulin M at 10 days after symptom onset. Anti-nucleocapsid, anti-spike 1 immunoglobulin G, anti-spike trimer, and anti-receptor-binding-domain immunoglobulin G and immunoglobulin E sera were detected at different titers 10 days after symptom onset. Several serum levels of chemokines/cytokines (Interferon-α, interferon-γ, interleukin-12/interleukin-23p40, interleukin-18, interferon gamma-induced protein-10, monocyte chemoattractant protein-1, monokine induced by gamma, macrophage inflammatory protein-1α, chemokine (C-C motif) ligand-5 , tumor necrosis factor-β1, Tumor necrosis factor-α) were detected, but interleukin-2, interleukin-4, interleukin-6, interleukin-8, and interleukin-17A were below the limit of detection., Interpretation and Conclusions: To our knowledge, this is the first study describing skin effects of a severe acute respiratory syndrome coronavirus 2 Omicron BA.5 variant breakthrough infection in a triple-vaccinated patient in Colombia. Several important mutations were found in the spike glycoprotein of the virus isolated; these mutations are associated with immune evasion and changes in antigenic properties of the virus. Physicians overseeing coronavirus disease 2019 cases should be aware of the potential skin effects of the infection. Pathogenesis of severe acute respiratory syndrome coronavirus 2 infection and its association with proinflammatory cytokines and chemokines may enhance the development of urticaria and other skin manifestations in immunized individuals. However, further studies are needed to better understand the complexity of coronavirus disease in such situations., (© 2023. The Author(s).)

We studied the prevalence of infection by trypanosomatid parasites in Didelphis marsupialis and its relationship with morphological/age aspects in a rural area of El Carmen de Bolivar, Colombia. Five visits were made to the Vereda El Alférez; each of which lasted three consecutive nights. During these visits, Tomahawk® traps were installed in the peridomestic and wild ecotopes of the Vereda El Alférez. Body measurements, sex and age were determined from the collected animals. Blood was extracted by cardiopuncture, after sedation, in order to obtain total deoxyribonucleic acid (DNA) and amplify the conserved region of the kinetoplast minicircle DNA (kDNA) of parasitic trypanosomatids. The association between morphological parameters of didelphids and their frequency of infection by parasitic trypanosomatids was determined by binomial regression. Thirty D. marsupialis specimens (60.0% females and 40.0% males/66.7% adults and 33.3% juveniles) were collected. Molecular diagnosis revealed a frequency of trypanosomatid parasite infection of 46.7%. Stage (p=0.024) was a determinant for infection. We discuss the role of D. marsupialis as a potential reservoir of parasitic trypanosomatids in the Vereda El Alférez.

Background: The crosstalk between the ubiquitin-proteasome and the immune system plays an important role in the health and pathogenesis of viral infection. However, there have been few studies of ubiquitin activation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We investigated the effect of ubiquitination on SARS-CoV-2 infection and patient prognosis by integrating published coronavirus disease 2019 (COVID-19) multi-transcriptome data and bioinformatics methods., Results: The differential expression of COVID-19 samples revealed changed ubiquitination in most solid and hollow organs, and it was activated in lymphatic and other immune tissues. In addition, in the respiratory system of COVID-19 patients, the immune response was mainly focused on the alveoli, and the expression of ubiquitination reflected increasing immune infiltration. Ubiquitination stratification could significantly differentiate patients' prognosis and inflammation levels through the general transcriptional analysis of the peripheral blood of patients with COVID-19. Moreover, high ubiquitination levels were associated with a favourable prognosis, low inflammatory response, and reduced mechanical ventilation and intensive care unit. Moreover, high ubiquitination promoted a beneficial immune response while inhibiting immune damage. Finally, prognostic stratification and biomarker screening based on ubiquitination traits played an important role in clinical management and drug development., Conclusion: Ubiquitination characteristics provides new ideas for clinical intervention and prognostic guidance for COVID-19 patients., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Orbital teratoma is a rare, vision-threatening, congenital neoplasm derived from all germ cell layers. The management of orbital teratoma is uncertain because of its rarity and variable severity. We present a case with complete tumor excision with preservation of vision and cosmesis. A 4-day-old female presented with progressive proptosis of the OD. She was born term following an uneventful pregnancy and delivery. MRI of the orbits showed a large right-sided mass centered within the intraconal space with heterogeneous signal intensity characteristics consistent with a teratoma. She underwent a right posterior orbitotomy. The tumor was wrapped around the optic nerve but was gradually separated from it and all other normal structures and delivered intact. Histology was compatible with an immature teratoma without evidence of malignancy. The patient is now 6 months old, visually attentive with no evidence of optic neuropathy, and has essentially normal appearance., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

SCF FBXW7 E3 ubiquitin ligase complex is a crucial enzyme of the ubiquitin proteasome system that participates in variant activities of cell process, and its component FBXW7 (F-box and WD repeat domain-containing 7) is responsible for recognizing and binding to substrates. The expression of FBXW7 is controlled by multiple pathways at different levels. FBXW7 facilitates the maturity and function maintenance of immune cells via functioning as a mediator of ubiquitination-dependent degradation of substrate proteins. FBXW7 deficiency or mutation results in the growth disturbance and dysfunction of immune cell, leads to the resistance against immunotherapy, and participates in multiple illnesses. It is likely that FBXW7 coordinating with its regulators and substrates could offer potential targets to improve the sensitivity and effects of immunotherapy. Here, we review the mechanisms of the regulation on FBXW7 and its tumor suppression role in immune filed among various diseases (mostly cancers) to explore novel immune targets and treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Xu, Zhang, Che, Wang, Shao, Qiu, Yu, Zhao and Zhang.)

Didelphis marsupialis is a primary reservoir of Trypanosoma cruzi , etiologic agent of American Trypanosomiasis-AT or Chagas Disease-CD, in America. Some findings of Trypanosoma rangeli have been recorded in this mammal, in sympatry with T. cruzi . In Los Montes de María, Bolívar, Colombian Caribbean, triatomine insects and potential parasite host has been registered, but little is known about the relationship between these parasites and D. marsupialis . We investigated the natural trypanosomatids infection rate in D. marsupialis , applying a parasitological and molecular diagnosis. Twenty D. marsupialis was investigated between 2018 and 2019 using 21 Tomahawk® traps placed on the sylvatic/domestic corridors. Blood was drawn by cardiopuncture after sedation. An aliquot of blood samples was cultured in Novy, Nicolle, McNeal/Roswell Park Memorial Institute medium at 24 °C/60 days for the detection of motile trypomastigotes. Parasite DNA was obtained by salting out methods from positive blood cultures. Trypanosomatids diagnosis was done by Polymerase Chain Reaction-sequencing of V7V8 region of 18S ribosomal RNA (18S-rRNA) gene. Amplicons were sequenced, and consensus sequences were aligned with reference sequences from GenBank. Four isolates corresponded to T. rangeli (20%) and one to T. cruzi (5%). The natural infection of D. marsupialis by T. rangeli and T. cruzi constitutes the first record of these parasites in didelphids in Los Montes de María and the first record of T. rangeli in this marsupial, in the Colombian Caribbean., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest and disclose no financial relationship with people or organizations that could bias this work., (© Indian Society for Parasitology 2021.)

Introduction: Trypanosoma cruzi, Trypanosoma rangeli and Leishmania spp. are parasites that coexist in several endemic areas. The identification of these parasites in hosts is important for the control programs., Methods: 216 samples from human blood (101), blood of other mammals (45) and triatomine intestinal content and hemolymph (70), from an endemic area of Venezuela, were analysed. The samples were evaluated by; serology (only humans) and PCR for T. cruzi in human, other mammals and triatomines, PCR for T. rangeli in mammals-including human and triatomines and PCR for Leishmania in mammals-including human., Results: The 9.9% of the human samples were positive for T. cruzi by serology, 11.9% by PCR, 4% for T. rangeli PCR and none for Leishmania spp. PCR. 60% of the samples of other mammals showed DNA amplification for T. cruzi, 42.2% for T. rangeli and 4.4% for Leishmania spp. 61.4% of the triatomine samples showed DNA amplification for T. cruzi and 10% for T. rangeli., Conclusions: High T. cruzi infection was detected in mammals and triatomines compared with T. rangeli. Low leishmanial infection was detected in other mammals. It is the first time that T. cruzi/T. rangeli coinfection, in humans, Canis familiaris (dog), and Bos Taurus (cow), were reported world-wide, and that this coinfection was described in Tamandua tetradactyla (anteater) from Venezuela. The coinfection T. cruzi/T. rangeli in mammals-including humans and triatomines, and coinfection T. cruzi/Leishmania spp. in non-human mammals, show the risk for trypanosomic zoonoses in this endemic area., (© 2021. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Background: There is increasing incidence of pulmonary nodules due to the promotion and popularization of low-dose computed tomography (LDCT) screening for potential populations with suspected lung cancer. However, a high rate of false-positive and concern of radiation-related cancer risk of repeated CT scanning remains a major obstacle to its wide application. Here, we aimed to investigate the clinical value of a non-invasive and simple test, named the seven autoantibodies (7-AABs) assay (P53, PGP9.5, SOX2, GAGE7, GUB4-5, MAGEA1, and CAGE), in distinguishing malignant pulmonary diseases from benign ones in routine clinical practice, and construct a neural network diagnostic model with the development of machine learning methods., Method: A total of 933 patients with lung diseases and 744 with lung nodules were identified. The serum levels of the 7-AABs were tested by an enzyme-linked Immunosorbent assay (ELISA). The primary goal was to assess the sensitivity and specificity of the 7-AABs panel in the detection of lung cancer. ROC curves were used to estimate the diagnosis potential of the 7-AABs in different groups. Next, we constructed a machine learning model based on the 7-AABs and imaging features to evaluate the diagnostic efficacy in lung nodules., Results: The serum levels of all 7-AABs in the malignant lung diseases group were significantly higher than that in the benign group. The sensitivity and specificity of the 7-AABs panel test were 60.7% and 81.5% in the whole group, and 59.7% and 81.1% in cases with early lung nodules. Comparing to the 7-AABs panel test alone, the neural network model improved the AUC from 0.748 to 0.96 in patients with pulmonary nodules., Conclusion: The 7-AABs panel may be a promising method for early detection of lung cancer, and we constructed a new diagnostic model with better efficiency to distinguish malignant lung nodules from benign nodules which could be used in clinical practice., Competing Interests: QS is employed by Amoy Diagnostics Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Chang, Yang, Lang, Zhang, Che, Xi, Zhang, Song, Zhou, Yang, Yang, Qu and Zhang.)

Objective: To determine the genetic diversity of Aedes aegypti in the Central-Alto Paraná cross-border road corridor of Paraguay, an area that has reports of dengue cases., Materials and Methods: Twenty adult females were selected from hatching Ae. aegypti eggs from households geolocated in the departments of Alto Paraná, Caaguazú, Cordillera and Central, between 2018 and 2019. DNA was extracted from the tissue of females for amplifying their polymorphic patterns by random amplification of polymorphic DNA by PCR (RAPD-PCR), using primers H3 and B03 in order to identify genetic parameters of population diversity. The relationships between mosquito populations according to locality were observed by unpaired arithmetic mean analysis. We used DIVA-GIS 7.3.0 and MAXENT to analyze the suitable areas of actual and potential geographic distribution of these Ae. aegypti populations., Results: Forty loci were identified by RAPD-PCR profiling, with moderate gene differentiation (Gst = 0.12). The cross-border corridor presented bioclimatic conditions for the presence of variant populations of Ae. aegypti, with precipitation in the warmest quarter and mean temperature in the driest quarter being determinant in the distribution., Conclusions: There is evidence of moderate genetic diversity in Ae. aegypti populations from areas that have reported dengue cases in the cross-border road corridor linking the Central and Alto Paraná departments of Paraguay. The study of genetic variability of Ae. aegypti is very useful for entomo-epidemiological surveillance and evaluation of possible resistance to chemical control.

Background: Increasing evidence shows that the ubiquitin-proteasome system has a crucial impact on lung adenocarcinoma. However, reliable prognostic signatures based on ubiquitination and immune traits have not yet been established., Methods: Bioinformatics was performed to analyze the characteristic of ubiquitination in lung adenocarcinoma. Principal component analysis was employed to identify the difference between lung adenocarcinoma and adjacent tissue. The ubiquitin prognostic risk model was constructed by multivariate Cox regression and least absolute shrinkage and selection operator regression based on the public database The Cancer Genome Atlas, with evaluation of the time-dependent receiver operating characteristic curve. A variety of algorithms was used to analyze the immune traits of model stratification. Meanwhile, the drug response sensitivity for subgroups was predicted by the "pRRophetic" package based on the database of the Cancer Genome Project., Results: The expression of ubiquitin genes was different in the tumor and in the adjacent tissue. The ubiquitin model was superior to the clinical indexes, and four validation datasets verified the prognostic effect. Additionally, the stratification of the model reflected distinct immune landscapes and mutation traits. The low-risk group was infiltrating plenty of immune cells and highly expressed major histocompatibility complex and immune genes, which illustrated that these patients could benefit from immune treatment. The high-risk group showed higher mutation and tumor mutation burden. Integrating the tumor mutation burden and the immune score revealed the patient's discrepancy between survival and drug response. Finally, we discovered that the drug targeting ubiquitin and proteasome would be a beneficial prospective treatment for lung adenocarcinoma., Conclusion: The ubiquitin trait could reflect the prognosis of lung adenocarcinoma, and it might shed light on the development of novel ubiquitin biomarkers and targeted therapy for lung adenocarcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Che, Jiang, Xu, Sun, Wu, Liu, Chang, Fan, Xi, Qiu, Ju, Pan, Zhang, Yang and Zhang.)

Introduction: The sensitivity and specificity of diagnostic techniques for Chagas disease depend largely on the antigens and targets used and on the immune response and characteristics of the infection of the population where it is applied, hence the need for evaluation of the diagnostic techniques available in a given area. So, the objective of this work was to evaluate two commercial kits for the immunological and molecular diagnosis of Chagas disease in endemic areas of Venezuela., Methods: The evaluated kits were: Chagas ELISA IgG+IgM® and Speed Oligo Chagas® (Vircell®, Granada, Spain). They were evaluated with 129 samples (35 from patients in the acute phase, 33 in the chronic phase, 31 from patients with other diseases, and 30 from healthy individuals). The results were compared with those obtained in the conventional ELISA and PCR-satellite DNA tests for Trypanosoma cruzi., Results: With Chagas ELISA IgG+IgM® a sensitivity of 94.1% and specificity of 93.4% were obtained, with Speed Oligo Chagas® a sensitivity of 92.6% and specificity of 100% were achieved, values similar to those showed by conventional ELISA and satDNA-PCR., Conclusion: The sensitivity and specificity of the commercial kits evaluated make them suitable for the diagnosis of Chagas disease in endemic areas of Venezuela., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Background: Lung cancer is the leading source of cancer-caused disability-adjusted life years. Medical cost burden impacts the well-being of patients through reducing income, cutting daily expenses, curtailing leisure activities, and depleting exhausting savings. The COmprehensive Score for Financial Toxicity (COST) was created and validated by De Souza and colleagues. Our study intends to measure the financial burdens of cancer therapy and investigate the link between financial toxicity and health-related quality of life (HRQoL) in an advanced lung cancer population. Methods: Patients aged ≥ 18 years with confirmed stage III to IV lung cancer were eligible. The COST questionnaire verified by de Souza et al. was used to identify financial toxicity. Multivariable linear regression analysis with log transformation univariate analysis and Pearson correlations were used to perform the analysis. Results: The majority of the patients (90.8%, n = 138/152) had an annual income of $50,000 ($7,775). The cohort's insurance situation was as follows: 64.5% of the cohort had social insurance, 20.4% had commercial insurance, and 22.0% had both. Patients who were younger age (50-59, P < 0.001), employed but on sick leave, and had lower income reported increased levels of financial toxicity ( P < 0.05). The risk factors for high financial toxicity: (i) younger age (50-59), (ii) <1 month of savings, and (iii) being employed but on sick leave. Increased financial toxicity is moderately correlated with a decrease in QoL. Conclusion: Poorer psychological status and specific demographics are linked to increased financial toxicity (lower COST). Financial toxicity has a modest relationship with HRQoL and may have a clear link with HRQoL measurements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Xu, Xi, Zhang, Zhou, Chang, Yang, Zhang, Wang, Ju, Yang, Chen, Che, Chen, Qu and Zhang.)

The objective of this study was to determine ocular manifestations of toxocariasis in schoolchildren. A study was conducted in two schools in the Anzoátegui state in Venezuela in 2019. The ELISA test was used to determine IgG antibodies against Toxocara spp. The families completed a questionnaire, and the children were clinically evaluated by pediatricians and ophthalmologists. 118 children participated, 18.6% presented anti-Toxocara spp. The clinical manifestations with a statistically significant association were allergic reactions, epiphora, and decreased visual acuity. The ophthalmological evaluation found keratitis, uveitis, iritis, retinal granuloma, endophthalmitis, amaurosis, leukocoria, retinal detachment and endotropia. The findings show a high frequency of eye disease in children with toxocariasis from a state of Venezuela.

Objective: To evaluate the relationship between pancreatic parenchyma loss and early postoperative hyperglycemia in patients with benign pancreatic diseases., Methods: A total of 171 patients with benign pancreatic tumors or chronic pancreatitis, whose preoperative fasting blood glucose (FBG) was normal and who underwent partial pancreatectomy were reviewed. The pancreatic volume was measured by CT imaging before and after the operation. According to their different pancreatic resection volume (PRV), 171 patients were divided into five groups: < 30%, 30%-39%, 40%-49%, 50%-59%, and ≥ 60%. The correlation between the PRV and postoperative FBG was investigated. According to the postoperative FBG value, the patients were divided into a hyperglycemia group (HG) and nonhyperglycemia group (non-HG) to explore the best cutoff value of the PRV between the two groups., Results: There were significant differences in the postoperative FBG among the five groups (PRV < 30%, 30%-39%, 40%-49%, 50%-59%, and ≥ 60%). The PRV was positively correlated with postoperative FBG in the benign tumor group and chronic pancreatitis group (R = 0.727 and 0.651, respectively). ROC curve analysis showed that the best cutoff value of the PRV between the HG (n = 84) and non-HG (n = 87) was 39.95% with an AUC = 0.898; the sensitivity was 89.29%, and the specificity was 82.76%., Conclusion: There was a linear positive correlation between the postoperative FBG level and PRV. Patients with a PRV ≥ 40% are more likely to develop early postoperative hyperglycemia., (© 2021. The Author(s).)

The development of new molecules for the treatment of leishmaniasis is, a neglected parasitic disease, is urgent as current anti-leishmanial therapeutics are hampered by drug toxicity and resistance. The pyrrolo[1,2-b]isoquinoline core was selected as starting point, and palladium-catalyzed Heck-initiated cascade reactions were developed for the synthesis of a series of C-10 substituted derivatives. Their in vitro leishmanicidal activity against visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis was evaluated. The best activity was found, in general, for the 10-arylmethyl substituted pyrroloisoquinolines. In particular, 2ad (IC 50  = 3.30 μM, SI > 77.01) and 2bb (IC 50  = 3.93 μM, SI > 58.77) were approximately 10-fold more potent and selective than the drug of reference (miltefosine), against L. amazonensis on in vitro promastigote assays, while 2ae was the more active compound in the in vitro amastigote assays (IC 50  = 33.59 μM, SI > 8.93). Notably, almost all compounds showed low cytotoxicity, CC 50  > 100 μg/mL in J774 cells, highest tested dose. In addition, we have developed the first Perturbation Theory Machine Learning (PTML) algorithm able to predict simultaneously multiple biological activity parameters (IC 50 , K i , etc.) vs. any Leishmania species and target protein, with high values of specificity (>98%) and sensitivity (>90%) in both training and validation series. Therefore, this model may be useful to reduce time and assay costs (material and human resources) in the drug discovery process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The cestode Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a severe helminthic zoonotic disease distributed in the Northern Hemisphere. The lifecycle of the parasite is mainly sylvatic, involving canid and rodent hosts. The absence of genetic data from most eastern European countries is a major knowledge gap, affecting the study of associations with parasite populations in Western Europe. In this study, EmsB microsatellite genotyping of E. multilocularis was performed to describe the genetic diversity and relatedness of 785 E. multilocularis isolates from four western and nine eastern European countries, as well as from Armenia and the Asian parts of Russia and Turkey. The presence of the same E. multilocularis populations in the Benelux resulting from expansion from the historical Alpine focus can be deduced from the main profiles shared between these countries. All 33 EmsB profiles obtained from 528 samples from the nine eastern European countries belonged to the European clade, except one Asian profile form Ryazan Oblast, Russia. The expansion of E. multilocularis seems to have progressed from the historical Alpine focus through Hungary, Slovakia, the Czech Republic and southern Poland towards Latvia and Estonia. Most of the samples from Asia belong to the Asian clade, with one EmsB profile shared between Armenia and Turkey, and two between Turkey and Russia. However, two European profiles were described from two foxes in Turkey, including one harboring worms from both European and Asian clades. Three EmsB profiles from three Russian samples were associated with the Arctic clade. Two E. multilocularis profiles from rodents from Lake Baikal belonged to the Mongolian clade, described for the first time here using EmsB. Further worldwide studies on the genetic diversity of E. multilocularis using both mitochondrial sequencing and EmsB genotyping are needed to understand the distribution and expansion of the various clades., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Waterlogging has negative effects on crop yield. Physiological and transcriptome data of two peanut cultivars [Zhongkaihua 1 (ZKH 1) and Huayu 39 (HY 39)] were studied under normal water supply and waterlogging stress for 5 or 10 days at the flowering stage. The results showed that the main stem height, the number of lateral branches, lateral branch length, and the stem diameter increased under waterlogging stress, followed by an increase in dry matter accumulation, which was correlated with the increase in the soil and plant analysis development (SPAD) and net photosynthetic rate (Pn) and the upregulation of genes related to porphyrin and chlorophyll metabolism and photosynthesis. However, the imbalance of the source-sink relationship under waterlogging was the main cause of yield loss, and waterlogging caused an increase in the sucrose and soluble sugar contents and a decrease in the starch content; it also decreased the activities of sucrose synthetase (SS) and sucrose phosphate synthetase (SPS), which may be due to the changes in the expression of genes related to starch and sucrose metabolism. However, the imbalance of the source-sink relationship led to the accumulation of photosynthate in the stems and leaves, which resulted in the decrease of the ratio of pod dry weight to total dry weight (PDW/TDW) and yield. Compared with ZKH 1, the PDW of HY 39 decreased more probably because more photosynthate accumulated in the stem and leaves of HY 39 and could not be effectively transported to the pod., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeng, Chen, Wang, Cao, Li, Xu, Chen, Xia, Dong, Huang, Wang, Zhang and Zhang.)

Direct test over the gut material from triatomine vectors and xenodiagnosis over mammalian hosts are classical techniques for Trypanosoma cruzi parasitological diagnosis. Nevertheless, negative results can be a source of uncertainty. Experimental models have allowed evaluating the tissue invasion of different strains of T. cruzi, but conventional techniques for tissue biopsies involve time-consuming and elaborated procedures and have low sensitivity. Gut material of collected triatomines (microscopically negative) (n = 114), material of mammal xenodiagnoses (microscopically negative) (n = 138), and biopsy material (microscopically negative) from experimentally infected animals (n = 34) with isolates from endemic areas of Chagas' disease from Venezuela were used for DNA extraction and PCR for the amplification of kinetoplast DNA (kDNA) and satellite DNA (sDNA) of T. cruzi. Positive PCR was observed in 53.6% of collected triatomine material, 15.8% of parasitological negative xenodiagnosis material, and 70.6% in biopsies, revealing underestimation by the parasitological tests and the valour of this analysis with preserved material. Anzoátegui was the state with the highest percentage of infection, and the triatomine species Rhodnius prolixus and Panstrongylus geniculatus had the highest percentages of infection. Didelphis marsupialis and Canis familiaris were the most infected by T. cruzi revealed by PCR of xenodiagnosis material. In addition, the PCR technique allowed demonstrating the invasion of T. cruzi in all tissues analyzed, constituting a molecular marker of tissue invasion.

Background: FBXW7 m 6 A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear., Methods: The correlation between FBXW7 and various genes related to m 6 A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m 6 A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m 6 A modification on LUAD development., Results: Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m 6 A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m 6 A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m 6 A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo., Conclusions: Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m 6 A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

Introduction: We define a fluid library as a library of samples of different biological fluids (from humans, animals or vectors) collected and properly stored on filter paper, which allows retrospective studies, especially of diagnosis or detection of infectious agents in these samples, using different techniques. The objective of this work was the retrospective diagnosis of American trypanosomiasis by PCR in a Venezuelan endemic area using a fluid library., Methods: A fluid library with samples that had been collected on filter paper, 5 years ago, was used for the detection of Trypanosoma cruzi DNA. 165 blood samples of humans, 30 samples of 25 animals (Didelphis marsupialis, Canis familiaris, Equus asinus and Felis catus) and 8 samples of vectors from endemic areas of Anzoátegui state, were analysed by PCR., Results: The results revealed that 16.4% of the humans samples were positive, 11.1% of those detected positive were children younger than 10 years old, and 26.72% young people aged 11-20 years, suggesting that T. cruzi infection has been active for the past two decades. 56% of the animal samples showed amplification; Didelphis marsupialis 66%, Canis familiaris 54.5%, Equus asinus 50%, and Felis catus 33.3%. On the other hand, positivity (50%) was detected in the studied vectors, of which the 3 most important species in Venezuela (Rhodnius prolixus, Triatoma maculata and Panstrongylus geniculatus) were involved., Conclusions: The PCR using a fluid library allowed the detection of T. cruzi DNA in old samples from the three host of the epidemiological chain, suggesting that retrospective diagnosis can be made through this strategy and demonstrate that there has been active transmission, which helps to clarify the epidemiological situation in areas where there are no previous reports.

Hydrochoerus hydrochaeris (capybara), is a widely distributed rodent in Latin America, with exploitation for food purposes and also used in leather industry products. The infection of this rodent by trypanosomatids may not be detected by parasitological methods, due to low parasitemias. The Capybaras blood samples from the Apure State were collected on filter paper, DNA was extracted and PCR was performed. The PCR technique was used for the detection of Trypanosoma cruzi satellite and kinetoplast DNA, T. rangeli miniexon, T. evansi RIME sequence, and DNA encoding ribosomal RNA and internal transcribed spacer 1 from Leishmania spp. Of the 16 evaluated samples, 12 (75%) were positive for T. cruzi, two for T. rangeli (12.5%), one for Leishmania spp. (6.3%) and none for T. evansi. Regarding coinfection, the two specimens infected with T. rangeli were also infected with T. cruzi (12.5%) and the positive sample for Leishmania spp. was also infected with T. cruzi (6.3%). The results shown in this study represent the first finding of T. cruzi infection, detected by molecular methods, world-wide and the first time that T. rangeli and Leishmania spp. have been found in capybaras. In addition, we report coinfections by T. cruzi/T. rangeli and T. cruzi/Leishmania spp. in H. hydrochaeris for the first time world-wide. Capybaras are widely managed as a source of animal protein, the results obtained require evaluating their possible role as a reservoir in trypanosomiasis and leishmaniasis. A 'One Health' approach through combination of ecological, veterinary and human health including the diagnosis and treatment of diseases of both humans and animals is essential for the development of more successful health programs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Objectives: Trypanosoma cruzi, the causative agent of American trypanosomiasis, has been reported in 180 mammalian species and 154 triatomines species of Neotropic. This is a clonal parasite with variable biological behaviour, associated with the genetics of the parasite and its hosts. To know the eco-pathogenic complex of this zoonosis, it was proposed to characterize T. cruzi isolates obtained from triatomines and domestic, peridomestic and wild mammals of the eastern and central-western regions of Venezuela., Methods: The positivity to T. cruzi was established and the isolates were genetically characterized by PCR amplification of the mini-exon gene, the DNA coding for 24Sa and 18S rRNA, and polymorphic sequences-RFLPs. The sampling sites were georeferenced using the MapSource Software and ArcGis 9.3 programs to generate distribution maps of the isolates., Results: Of the 460 hosts (205 triatomines and 255 mammals), 49% were positive for the parasite. On the other hand, 38 isolates obtained from the triatomines and 23 isolates obtained from mammals were evaluated. The TcI genotype predominated in most of the isolates; however, in those obtained from triatomines the presence of the TcIII genotype in single infections and TcI + TcIII or TcI + TcIV in mixed infections was also evidenced., Interpretation & Conclusion: There is a possibility that the triatomines act as biological syringes for these genotypes associated exclusively to them. The heterogeneity in T. cruzi isolates demonstrated the complexity of parasitosis in these regions, presenting its control and prevention as a challenge., Competing Interests: None

Leaf area index (LAI) is used to predict crop yield, and unmanned aerial vehicles (UAVs) provide new ways to monitor LAI. In this study, we used a fixed-wing UAV with multispectral cameras for remote sensing monitoring. We conducted field experiments with two peanut varieties at different planting densities to estimate LAI from multispectral images and establish a high-precision LAI prediction model. We used eight vegetation indices (VIs) and developed simple regression and artificial neural network (BPN) models for LAI and spectral VIs. The empirical model was calibrated to estimate peanut LAI, and the best model was selected from the coefficient of determination and root mean square error. The red (660 nm) and near-infrared (790 nm) bands effectively predicted peanut LAI, and LAI increased with planting density. The predictive accuracy of the multiple regression model was higher than that of the single linear regression models, and the correlations between Modified Red-Edge Simple Ratio Index (MSR), Ratio Vegetation Index (RVI), Normalized Difference Vegetation Index (NDVI), and LAI were higher than the other indices. The combined VI BPN model was more accurate than the single VI BPN model, and the BPN model accuracy was higher. Planting density affects peanut LAI, and reflectance-based vegetation indices can help predict LAI.

Drought negatively affects the growth and yield of terrestrial crops. Seed priming, pre-exposing seed to a compound, could induce improved tolerance and adaptation to stress in germinated plants. To understand the effects and regulatory mechanism of seed priming with brassinosteroid (BR) on peanut plants, we treated seeds with five BR concentrations and examined dozens of physiological and biochemical features, and transcriptomic changes in leaves under well-watered and drought conditions. We found optimal 0.15 ppm BR priming could reduce inhibitions from drought and increase the yield of peanut, and priming effects are dependent on stage of plant development and duration of drought. BR priming induced fewer differentially expressed genes (DEGs) than no BR priming under well-watered condition. Drought with BR priming reduced the number of DEGs than drought only. These DEGs were enriched in varied gene ontologies and metabolism pathways. Downregulation of DEGs involved in both light perceiving and photosynthesis in leaves is consistent with low parameters of photosynthesis. Optimal BR priming partially rescued the levels of growth promoting auxin and gibberellin which were largely reduced by drought, and increased levels of defense associated abscisic acid and salicylic acid after long-term drought. BR priming induced many DEGs which function as kinase or transcription factor for signal cascade under drought. We proposed BR priming-induced regulatory responses will be memorized and recalled for fast adaptation in later drought stress. These results provide physiological and regulatory bases of effects of seed priming with BR, which can help to guide the framing improvement under drought stress.

Intercropping improves land utilization with more crops grown together; however, shorter crops in intercropping experience stress, being shaded by the taller crops. Systematic changes in phenotype, physiology, yield, and gene regulation under shade stress in peanut are largely unknown, although shade responses have been well analyzed in model plants. We exposed peanut plants to simulated 40% and 80% shade for 15 and 30 days at the seedling stage, flowering stage, and both stages. Shade caused the increased elongation growth of the main stem, internode, and leaf, and elongation was positively associated with auxin levels. Shade stress reduced peanut yield. Further comparative RNA-seq analyses revealed expressional changes in many metabolism pathways and common core sets of expressional regulations in all shade treatments. Expressional downregulation of most genes for light-harvesting and photosynthesis agreed with the observed decreased parameters of photosynthesis processes. Other major regulations included expressional downregulation of most core genes in the sucrose and starch metabolism, and growth-promoting genes in plant hormone signal pathways. Together, the results advance our understanding of physiological and molecular regulation in shade avoidance in peanut, which could guide the breeding designing in the intercropping system., Competing Interests: The authors declare no conflicts of interests.

Objective: To determine the incidence and the clinical, bacteriological and cerebrospinal fluid characteristics of neonatal meningitis in Lima hospitals., Materials and Methods: An observational, multicenter study was conducted in six hospitals in the city of Lima during 1 year of epidemiological surveillance., Results: The cumulative hospital incidence was 1.4 cases per 1000 live births. A total of 53 cases of neonatal meningitis were included, 34% (18/53) were early and 66% (35/53) late. The associated maternal factors were meconium-stained amniotic fluid and urinary tract infection. Insufficient prenatal check-ups were found in 58.8% (30/51). The most associated neonatal factor was sepsis. The main symptoms were fever, irritability, hypoactivity and respiratory distress. Pleocytosis in cerebrospinal fluid (CSF) was significant, without predominance of polymorphonuclear lymphocytes (PMN), hypoglycorrhagia and proteinorrhagia. The most frequent pathogens isolated were Escherichia coli and Listeria monocytogenes., Conclusions: The hospital incidence of neonatal meningitis was 1.4 per 1000 live births, being ten times higher in preterm infants. Breathing difficulty was the most frequent symptom in the early stage, while fever and irritability in the late stage. CSF showed pleocytosis without predominance of PMN. The most frequent germs were Escherichia coli and Listeria monocytogenes. Ventriculitis and hydrocephalus were the most common neurological complications.

Umbilical cord mesenchymal stromal cells (UC-MSC) are promising candidates for cell therapy due to their potent multilineage differentiation, enhanced self-renewal capacity, and immediate availability for clinical use. Clinical experience has demonstrated satisfactory biosafety profiles and feasibility of UC-MSC application in the allogeneic setting. However, the use of UC-MSC for bone regeneration has not been fully established. A major challenge in the generation of successful therapeutic strategies for bone engineering lies on the combination of highly functional proosteogenic MSC populations and bioactive matrix scaffolds. To address that, in this study we proposed a new approach for the generation of bone-like constructs based on UC-MSC expanded in human platelet lysate (hPL) and evaluated its potential to induce bone structures in vivo . In order to obtain UC-MSC for potential clinical use, we first assessed parameters such as the isolation method, growth supplementation, microbiological monitoring, and cryopreservation and performed full characterization of the cell product including phenotype, growth performance, tree-lineage differentiation, and gene expression. Finally, we evaluated bone-like constructs based on the combination of stimulated UC-MSC and collagen microbeads for in vivo bone formation. UC-MSC were successfully cultured from 100% of processed UC donors, and efficient cell derivation was observed at day 14 ± 3 by the explant method. UC-MSC maintained mesenchymal cell morphology, phenotype, high cell growth performance, and probed multipotent differentiation capacity. No striking variations between donors were recorded. As expected, UC-MSC showed tree-lineage differentiation and gene expression profiles similar to bone marrow- and adipose-derived MSC. Importantly, upon osteogenic and endothelial induction, UC-MSC displayed strong proangiogenic and bone formation features. The combination of hPL-expanded MSC and collagen microbeads led to bone/vessel formation following implantation into an immune competent mouse model. Collectively, we developed a high-performance UC-MSC-based cell manufacturing bioprocess that fulfills the requirements for human application and triggers the potency and effectivity of cell-engineered scaffolds for bone regeneration., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Ingrid Silva-Cote et al.)

American trypanosomiasis and leishmaniases are diseases caused by protozoans of the Trypanosomatidae family. In Venezuela, although several endemic foci of both diseases coincide, there are no reports of coinfection in mammals. The molecular diagnosis of the coinfection T. cruzi-Leishmania spp. was done in 527 blood samples collected on filter paper of several species of mammals (Canis familiaris, Equus asinus, Didelphis marsupialis, Equus mulus, Rattus rattus, Equus caballus, Artibeus fraterculus, Felis catus, Sus scrofa, Bos taurus, Capra hircus and Sciurus granatensis) from the states Cojedes, Aragua, Anzoátegui, Guárico, Miranda and Capital District. The T. cruzi infection was determined through PCR amplification of DNA of kinetoplast minicircles (kDNA) and satellite DNA (sDNA). The Leishmania spp. infection was detected by Leishmania nested PCR (Ln-PCR), and ribosomal DNA internal transcribed spacer 1 PCR (ITS1-PCR). The percentage of infection by T. cruzi was 23.5%, by Leishmania spp. 12.9% and coinfection was 5.7%. D. marsupialis was the species with the highest percentage of infection for each parasitosis (T. cruzi 34.3%, Leishmania spp. 20.0%) and coinfection (14.3%). Anzoátegui was the state with the highest percentage of infection for each parasitosis (T. cruzi 64.9%, Leishmania spp. 64.9%) and coinfection (43.2%). Infections were determined in species not reported as natural reservoirs of T. cruzi (E. asinus and E. mulus) and of Leishmania spp. (E. mulus and S. scrofa). Coinfection was a frequent phenomenon in mammals in several co-endemic zones evaluated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: To know the natural infestation by triatominae and their infection by Trypanosoma cruzi (T. cruzi) in Acrocomia Aculeata (A. aculeata) or coyol palm in the state of Anzoátegui, Venezuela., Materials and Methods: Triatominic infestation and its infection by T. cruzi was studied in non-affected A. aculeata in phytosanitary campaigns. The presence of the parasite was determined by microscopy and PCR-kDNA, and its characterization was made by means of molecular markers., Results: Fourteen palm trees with triatominic infestation were found; 48.8% of the individuals corresponded to Rhodnius prolixus and 48.2% to Maculata Triatoma, with ontogenetic development towards adult. The parasitology and molecular tests, their typical morphology and the infection in the murine model revealed the presence of T. cruzi in an average of 54,8%, for both species of triatominae, with circulation of the TcI genotype of T. cruzi., Conclusions: The infestation of coyol palm trees with Rhodnius prolixus and Maculata Triatoma was reported for the state of Anzoátegui in Venezuela, as well as the presence of TcI sub-populations of T. cruzi, being this palm tree the peridomicilar habitat of the triatominae-T. cruzi binomial and possible bioindicador of risk of infection for surrounding human populations.

Red fox (Vulpes vulpes) is the most widely distributed canid in the world and an important source of multiple zoonotic pathogens capable of causing life-threatening diseases, such as rabies and alveolar echinococcosis. Informing general public of potential risks related to foxes is becoming more important since the fox densities have increased in many countries and the species is colonizing urban areas in Europe and around the world with increasing pace, bringing zoonotic pathogens to the immediate neighbourhood of humans and their companion animals. The aim of this study was to examine the parasite fauna of red foxes in Estonia. We found in Estonian foxes a total of 17 endoparasite taxa, including ten zoonotic species. All the analysed individuals were infected and the average parasite species richness was 6·37. However, the infection rates varied to a very large extent for different parasite species, ranging from 0·9 to 91·5%. Of zoonotic species, the highest infection rate was observed for Alaria alata (90·7%), Eucoleus aerophilus (87·6%) and Uncinaria stenocephala (84·3%). The prevalence of tapeworm Echinococcus multilocularis, a causative agent for alveolar echinococcosis, was also relatively high (31·5%), presenting a potential risk to human health.

The emerging vector of Chagas disease, Triatoma maculata (Hemiptera, Reduviidae), is one of the most widely distributed Triatoma species in northern South America. Despite its increasing relevance as a vector, no consistent picture of the magnitude of genetic and phenetic diversity has yet been developed. Here, several populations of T. maculata from eleven Colombia and Venezuela localities were analyzed based on the morphometry of wings and the mitochondrial NADH dehydrogenase subunit 4 (ND4) gene sequences. Our results showed clear morphometric and genetic differences among Colombian and Venezuelan populations, indicating high intraspecific diversity. Inter-population divergence is suggested related to East Cordillera in Colombia. Analyses of other populations from Colombia, Venezuela, and Brazil from distinct eco-geographic regions are still needed to understand its systematics and phylogeography as well as its actual role as a vector of Chagas disease., (© 2016 The Society for Vector Ecology.)

The raccoon dog (Nyctereutes procyonoides) is a canid that is indigenous in East Asia and alien in Europe, where it was introduced more than half a century ago. The aim of this study was to compare the parasite faunas associated with raccoon dogs in their native and introduced ranges, and to identify zoonotic parasite species. We examined 255 carcasses of hunted raccoon dogs from Estonia and recorded a total of 17 helminth species: 4 trematodes, 4 cestodes and 9 nematodes. The most prevalent parasite species were Uncinaria stenocephala (97.6%) and Alaria alata (68.3%). Average parasite species richness was 2.86 (the highest was 9) and only two animals were not parasitized at all. Although the infection intensity was determined by weight and not by sex, all animals infected with more than five helminth species were males. We also found that animals infected with higher numbers of helminth species fed significantly more on natural plants. Intentional consumption of grass may represent a self-medicating behaviour among raccoon dogs. We included the Estonian data into a wider comparison of raccoon dog parasite faunas and found a total of 54 helminth taxa, including 28 of zoonotic potential. In Europe, raccoon dogs are infected with a minimum of 32 helminth species of which 19 are zoonotic; in the native range they are infected with 26 species of which 17 are zoonotic. Most species were nematodes or trematodes, with fewer cestodes described. The recent increase in the number and range of raccoon dogs in Europe and the relatively high number of zoonotic parasite taxa that it harbours suggests that this species should be considered an important source of environmental contamination with zoonotic agents in Europe., (Copyright © 2016 Elsevier B.V. All rights reserved.)