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Bovine babesiosis, caused by the protozoan Babesia bigemina, is one of the most important hemoparasite diseases of cattle in Mexico and the world. An attenuated B. bigemina strain maintained under in vitro culture conditions has been used as a live attenuated vaccine; however, the biological mechanisms involved in attenuation are unknown. The objective of this study was to identify, through a comparative transcriptomics approach, the components of the B. bigemina virulent parasites that are differentially expressed in vivo, as opposed to those expressed by B. bigemina attenuated vaccine parasites when inoculated into naïve cattle. The biological material under study was obtained by inoculating spleen-intact cattle with infected erythrocytes containing either the attenuated strain or a virulent field strain. After RNA extraction, transcriptomic analysis (RNA-seq) was performed, followed by bioinformatic Differential Expression (DE) analysis and Gene Ontology (GO) term enrichment. The high-throughput sequencing results obtained by analyzing three biological replicates for each parasite strain ranged from 9,504,000 to 9,656,000, and 13,400,000 to 15,750,000 reads for the B. bigemina attenuated and virulent strains, respectively. At least 519 differentially expressed genes were identified in the analyzed strains. In addition, GO analysis revealed both similarities and differences across the three categories: cellular components, biological processes, and molecular functions. The attenuated strain of B. bigemina derived from in vitro culture presents global transcriptomic changes when compared to the virulent strain. Moreover, the obtained data provide insights into the potential molecular mechanisms associated with the attenuation or pathogenicity of each analyzed strain, offering molecular markers that might be associated with virulence or potential vaccine candidates.

Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators by mast cells and basophils. Although anaphylaxis is often under-communicated and thus underestimated, its incidence appears to have risen over recent decades. Drugs are among the most common triggers in adults, being analgesics and antibiotics the most common causal agents. Anaphylaxis can be caused by immunologic or non-immunologic mechanisms. Immunologic anaphylaxis can be mediated by IgE-dependent or -independent pathways. The former involves activation of Th2 cells and the cross-linking of two or more specific IgE (sIgE) antibodies on the surface of mast cells or basophils. The IgE-independent mechanism can be mediated by IgG, involving the release of platelet-activating factor, and/or complement activation. Non-immunological anaphylaxis can occur through the direct stimulation of mast cell degranulation by some drugs, inducing histamine release and leading to anaphylactic symptoms. Work-up of a suspected drug-induced anaphylaxis should include clinical history; however, this can be unreliable, and skin tests should also be used if available and validated. Drug provocation testing is not recommended due to the risk of inducing a harmful reaction. testing can help to confirm anaphylaxis by analyzing the release of mediators such as tryptase or histamine by mast cells. When immunologic mechanisms are suspected, serum-sIgE quantification or the use of the basophil activation test can help confirm the culprit drug. In this review, we will discuss multiple aspects of drug-induced anaphylaxis, including epidemiology, mechanisms, and diagnosis.

Chagas disease was originally reported in Panama in 1931. Currently, the best knowledge of this zoonosis is restricted to studies done in historically endemic regions. However, little is known about the distribution and epidemiology of Chagas disease in other rural areas of the country. A cross-sectional descriptive study was carried out between May 2005 - July 2008 in four rural communities of the Santa Fe District, Veraguas Province. The study included an entomologic search to collect triatomines, bloodmeal type identification and infection rate with trypanosomes in collected vectors using a dot- blot and PCR analysis, genotyping of circulating Trypanosoma cruzi (mini-exon gene PCR analysis) and the detection of chagasic antibodies among inhabitants. The vector Rhodnius pallescens was more frequently found in La Culaca and El Pantano communities (788 specimens), where it was a sporadic household visitor. These triatomines presented darker coloration and larger sizescompared with typical specimens collected in Central Panama. Triatoma dimidiata was more common in Sabaneta de El Macho (162 specimens). In one small sub-region (El Macho), 60% of the houses were colonized by this vector. Of the examined R. pallescens, 54.7.0% (88/161) had fed on Didelphis marsupialis, and 24.6% (34/138) of T. dimidiata specimens collected inside houses were positive for human blood. R. pallescens presented an infection index with T. cruzi of 17.7% (24/136), with T. rangeli of 12.5% (17/136) and 50.7% (69/136) were mixed infections. In 117 T. dimidiata domestic specimens the infection index with T. cruzi was 21.4%. Lineage I of T. cruzi was confirmed circulating in these vectors. A T. cruzi infection seroprevalence of 2.3% (24/1,056) was found in this population. This is the first report of Chagas disease endemicity in Santa Fe District, and it should be considered a neglected public health problem in this area of Panama.

Coastal regions in Mexico face significant exposure to hydrometeorological hazards, often resulting in severe flooding and socioeconomic disruption. This study assesses the hydrometeorological resilience of the Veracruz–Boca del Río Conurbation (VBC), a region comprising two coastal municipalities with shared hazard exposure despite distinct governance structures. The hydrometeorological resilience evaluation employs the City Resilience Index (CRI), developed by Bahena which integrates the Technical Resilience Index (TRI) and the Technical Profile of Resilience (TPR) across nine hierarchical indicators. Results reveal moderate resilience levels—59.83% for Veracruz and 58.32% for Boca del Río—with Disaster Risk Reduction Plans and Vital Services indicators as the strongest contributors, while Risk Assessments and Budget Allocation for Emergency Response indicators scored lowest due to limited municipal data. These findings highlight the need for enhanced data transparency, institutional coordination, and resource allocation in disaster management. Beyond its local significance, this study advances the global understanding of resilience assessment frameworks in data-scarce contexts, offering insights applicable to similar regions worldwide. As the first hydrometeorological resilience assessment for the VBC, this research provides a methodological and empirical foundation for future studies and informs targeted resilience strategies for Mexico’s coastal urban areas.

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax . Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 59 P . vivax samples from Panama. The P . vivax samples were collected from two periods (2007–2009 and 2017–2019) to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a highly genetically related lineage (termed CL1) was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007–2019) and all regions of the country. We also found a second, smaller clonal lineage (termed CL2) of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P . vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of Panamanian P . vivax samples not belonging to either CL1 or CL2 clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P . vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P . vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination.

Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although the malaria incidence in Panama is low, a recent outbreak resulted in a 6-fold increase in reported cases. We hypothesized that parasites sampled from this epidemic might be related and exhibit a clonal population structure. We tested the genetic relatedness of parasites, using informative single-nudeotide polymorphisms and drug resistance loci. We found that parasites were clustered into 3 clonal subpopulations and were related to parasites from Colombia. Two clusters of Panamanian parasites shared identical drug resistance haplotypes, and all clusters shared a chloroquine-resistance genotype matching the pfcrt haplotype of Colombian origin. Our findings suggest these resurgent parasite populations are highly clonal and that the high clonality likely resulted from epidemic expansion of imported or vestigial cases. Malaria outbreak investigations that use genetic tools can illuminate potential sources of epidemic malaria and guide strategies to prevent further resurgence in areas where malaria has been eliminated.

Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Hyperuricemia has been associated with renal disease. Because glomerular hemodynamic alterations critically contribute to initiation and progression of renal disease, we evaluated the effect of mild hyperuricemia in glomerular microcirculatory changes in rats under normal conditions and with renal injury induced by subtotal renal ablation (RK). Hyperuricemia was induced in normal and remnant kidney (RK) rats on a normal sodium diet by administration of oxonic acid (OA). To prevent hyperuricemia, allopurinol (AP) was administered concomitantly. Glomerular hemodynamics were evaluated by micropuncture techniques. Systolic blood pressure (SBP), proteinuria, arterial morphology, and serum uric acid were measured. In RK rats, glomerulosclerosis, fibrosis, and inflammatory cell infiltration (CD5+) were also assessed. In normal rats, hyperuricemia resulted in afferent arteriole thickening associated with renal cortical vasoconstriction [single nephron glomerular filtration rate (SNGFR) -35%, P < 0.05) and glomerular hypertension (P < 0.05). Allopurinol treatment prevented structural and functional alterations. In RK rats, hyperuricemia produced more renal vascular damage than control animals coupled with severe cortical vasoconstriction (SNGFR -40%, P < 0.05) and persistent glomerular hypertension. Allopurinol partially prevented cortical vasoconstriction, and fully prevented arteriolopathy and glomerular hypertension associated with significantly less infiltration of CD5+ cells. Hyperuricemia induces arteriolopathy of preglomerular vessels, which impairs the autoregulatory response of afferent arterioles, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening produces severe renal hypoperfusion. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis, as well as arterial hypertension. These studies provide a potential mechanism by which hyperuricemia can mediate hypertension and renal disease.

BackgroundOn the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved chimeric antigen receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and costimulation of T cells will facilitate clinical development of CD137 agonists in the clinic.MethodsWe used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored on treatment with agonist anti-CD137 monoclonal antibodies (mAbs). Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 mAb (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISA and Luminex. Flow cytometry was used to monitor CD137 surface expression.ResultsCD137 costimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 costimulation inside subcutaneously implanted Matrigel plugs. The CD137 signaling domain-containing CAR T cells readily released sCD137 and acquired CD137 surface expression on antigen recognition. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137.ConclusionsCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic costimulatory activity elicited by agonist CD137-targeted agents.