Accelerating Patterned Vascularization Using Granular Hydrogel Scaffolds and Surgical Micropuncture.

Bulk hydrogel scaffolds are common in reconstructive surgery. They allow for the staged repair of soft tissue loss by providing a base for revascularization. Unfortunately, they are limited by both slow and random vascularization, which may manifest as treatment failure or suboptimal repair. Rapidly inducing patterned vascularization within biomaterials has profound translational implications for current clinical treatment paradigms and the scaleup of regenerative engineering platforms. To address this long-standing challenge, a novel microsurgical approach and granular hydrogel scaffold (GHS) technology are co-developed to hasten and pattern microvascular network formation. In surgical micropuncture (MP), targeted recipient blood vessels are perforated using a microneedle to accelerate cell extravasation and angiogenic outgrowth. By combining MP with an adjacent GHS with precisely tailored void space architecture, microvascular pattern formation as assessed by density, diameter, length, and intercapillary distance is rapidly guided. This work opens new translational opportunities for microvascular engineering, advancing reconstructive surgery, and regenerative medicine.

The Oxente Chagas Bahia Project: evaluating the efficacy of a rapid diagnostic test and treatments for Chagas disease.

Chagas disease (CD), caused by Trypanosoma cruzi, is a life-threatening neglected anthropozoonosis primarily transmitted by triatomine bugs. Affecting an estimated 5.7 million people globally, CD has significant morbidity and mortality, particularly in Latin America. The Oxente Chagas Bahia Project aims to screen approximately 30,000 individuals, validate a rapid diagnostic test in a real-world setting, and provide crucial data on its diagnostic performance and cost-effectiveness. Additionally, a biobank will be established to support further research on disease biomarkers and treatment cure rates. By enhancing access to timely diagnosis and treatment, the project will evaluate a strategy to reduce the CD burden.

Evaluation of Semiautomatic and Deep Learning-Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.

Development of a Nanoformulation for Oral Protein Administration: Characterization and Preclinical Orofacial Antinociceptive Effect.

Nanoencapsulation is a valid alternative for the oral administration of peptide drugs and proteins, as nanoparticles protect them from proteolytic degradation in the gastrointestinal tract and promote the absorption of these macromolecules. The orofacial antinociceptive effect of frutalin (FTL), through the intraperitoneal route, has already been proven. This study aimed to develop, characterize, and evaluate the orofacial antinociceptive activity of an oral formulation containing FTL in acute and neuropathic preclinical tests. Nanoencapsulated FTL was administered by oral route. The acute nociceptive behavior was induced by administering capsaicin to the upper lip and NaCl to the right cornea. The nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The neuropathic pain model involved infraorbital nerve transection (IONX), which induced mechanical hypersensitivity and was assessed by von Frey stimulation. Trpv1 gene expression was analyzed in the trigeminal ganglion. The analyzed sample did not show any cytotoxicity; 52.2% of the FTL was encapsulated, and the size of the nanocapsule was less than 200 nm, the polydispersion was 0.361, and the zeta potential was - 5.87 and - 12.8 mV, with and without FTL, respectively. Nanoencapsulated FTL administered by oral route had an orofacial antinociceptive effect in acute and neuropathic rodent models. The antinociceptive effect of FTL was prevented by ruthenium red, but not by camphor. FTL reduced Trpv1 gene expression. FTL promotes orofacial antinociception, probably due to the antagonism of TRPV1 channels, and the nanoformulation represents an effective method for the oral administration of this protein. HIGHLIGHTS: • Nanoformulation for oral protein administration. • Nanocapsule containing FTL prevents orofacial nociceptive acute and neuropathic pain. • Frutalin promotes orofacial antinociception behavior antagonism of TRPV1 channels.

123I-FP-CIT SPECT in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease: a new quantitative analysis of autopsy confirmed cases.

PURPOSE: The aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and Parkinson's disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans. METHODS: Thirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR). RESULTS: Patients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC. CONCLUSIONS: This study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.

Assessment of Liaison XL Murex Chagas diagnostic performance in blood screening for Chagas disease using a reference array of chimeric antigens.

BACKGROUND: Chagas disease (CD) serological screening at blood banks is usually performed by a single highly sensitive serological assay, with chemiluminescent immunoassays (CLIAs) being the method of choice. CLIAs employ recombinant, fusion peptides and/or chimeric antigens that selectively capture anti-Trypanosoma cruzi antibodies. However, despite high sensitivity, the ability of these tests to identify CD-positive cases should be evaluated against T. cruzi strains circulating in specific locales. Herein, we used a latent class analysis (LCA) approach employing an array of four chimeric antigens to assess the diagnostic performance of the Liaison XL Murex Chagas CLIA for the detection of anti-T. cruzi IgG in serum samples. STUDY DESIGN AND METHODS: The study included a panel of 5014 serum samples collected from volunteer blood donors at the Hematology and Hemotherapy Foundation of the State of Bahia, submitted to anti-T. cruzi antibody detection using Liaison Chagas CLIA and LCA as a reference test in the absence of a gold standard. RESULTS: LCA classified 4993 samples as negative, while positivity for T. cruzi antibodies was predicted in 21 samples. Compared with LCA, CLIA demonstrated sensitivity and specificity of 76.2% and 99.5%, respectively, providing an overall accuracy of 99.4%. DISCUSSION: In blood banks lacking a de facto highly sensitive screening immunoassay, the low sensitivity offered by Liaison Chagas CLIA renders it unsuitable for standalone use in serological screening procedures for CD. Moreover, blood banks are encouraged to carefully assess the ability of diagnostic methods to identify local T. cruzi strains in circulation.

Are lesion features reproducible between 18F-FDG PET/CT images when acquired on analog or digital PET/CT scanners?

OBJECTIVES: To compare lesion features extracted from 18F-FDG PET/CT images acquired on analog and digital scanners, on consecutive imaging data from the same subjects. METHODS: Whole-body 18F-FDG PET/CT images from 55 oncological patients were acquired twice after a single 18F-FDG injection, with a digital and an analog PET/CT scanner, alternately. Twenty-nine subjects were examined first on the digital, and 26 first on the analog equipment. Image reconstruction was performed using manufacturer standard clinical protocols and protocols that fulfilled EARL1 specifications. Twenty-five features based on lesion standardized uptake value (SUV) and geometry were assessed. To compare these features, intraclass correlation coefficient (ICC), relative difference (RD), absolute value of RD (|RD|), and repeatability coefficient (RC) were used. RESULTS: In total, 323 18F-FDG avid lesions were identified. High agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both scanners' imaging data, especially when reconstruction protocols fulfilled EARL1 specifications. For EARL1 reconstruction images, the features frequently used in clinics, SUVmax, SUVpeak, SUVmean, metabolic tumor volume, and total lesion glycolysis, reached an ICC of 0.92, 0.95, 0.87, 0.98, and 0.98, and a median RD (digital-analog) of 3%, 5%, 4%, - 3% and 1%, respectively. Using standard reconstruction protocols, the ICC were 0.84, 0.93, 0.80, 0.98, and 0.98, and the RD were 20%, 11%, 13%, - 7%, and 7%, respectively. CONCLUSION: Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work. This is especially important for multicenter studies and patient follow-ups. KEY POINTS: • Using manufacturer standard clinical reconstruction protocols, lesions SUV was significantly higher when using the digital scanner, especially the SUVmax that was approximately 20% higher. • High agreement was obtained for the majority of the lesion features when using reconstruction protocols that fulfilled EARL1 specifications. • Longitudinal patient studies can be performed interchangeably between digital and analog scanners when both fulfill EARL1 specifications.

Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators.

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.

Cross-Reactivity Using Chimeric Trypanosoma cruzi Antigens: Diagnostic Performance in Settings Where Chagas Disease and American Cutaneous or Visceral Leishmaniasis Are Coendemic.

Chimeric T. cruzi antigens have been proposed as a diagnostic tool for chronic Chagas disease (CD) in both settings where Chagas disease is endemic and those where it is not endemic. Antibody response varies in accordance to each T. cruzi strain, presenting challenges to the use of antigens lacking demonstrated cross-reactivity with Leishmania spp. Our group expressed four chimeric proteins (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) and previously assessed their diagnostic performance to determine cross-reactivity with Leishmania spp. Here, we validated our findings using serum samples from different Brazilian geographic areas reporting endemic Chagas disease, endemic visceral or American cutaneous leishmaniasis (ACL), or both. Overall, 829 serum samples were evaluated using commercial and IBMP enzyme-linked immunosorbent assays. Due to the absence of a reference assay to diagnosis CD, latent class analysis (LCA) was performed through the use of a statistical model. The incidence of cross-reactivity for ACL-positive samples varied from 0.35% (IBMP-8.3) to 0.70% (IBMP-8.1 and IBMP-8.2). Regarding visceral leishmaniasis (VL)-positive samples, the IBMP-8.2 and IBMP-8.3 antigens cross-reacted with six (3.49%) and with only one sample (0.58%), respectively. No cross-reactivity with either ACL or VL was observed for the IBMP-8.4 antigen. Similarly, no cross-reactions were found when VL-positive samples were assayed with IBMP-8.1. The agreement among the results obtained using IBMP antigens ranged from 97.3% for IBMP-8.2 and 99% for IBMP-8.1 and IBMP-8.3 to 100% for IBMP-8.4, demonstrating almost perfect agreement with LCA. Accordingly, in light of the negligible cross-reactivity with both ACL and VL, we suggest the use of IBMP antigens in regions where T. cruzi and Leishmania spp. are coendemic.

Arabica coffee fruits phenology assessed through degree days, precipitation, and solar radiation exposure on a daily basis.

Knowledge regarding reproductive cycle duration is important in terms of scheduling harvests and estimating coffee cultivars adaptability. Nine Coffea arabica cultivars were evaluated during two successive reproductive cycles. Dates of occurrence of the major blossoms, and the green and ripe fruits, on 64 branches for each cultivar, were registered during each reproductive cycle. These dates were used to calculate the duration of the fruit development (blossom to green) and ripening (green to ripe) phases, the quantities of degree days, precipitation, and solar radiation accumulated throughout each phase, and also degree days, precipitation, and radiation on a daily basis, all of which are novelties in coffee research. The differences between cultivars and reproductive cycles were tested by ANOVA. Cultivars were grouped in clusters according to the above-cited variables. Principally, the daily quantities of degree days and precipitation determined the differences between reproductive cycles and coffee cultivars during development phases. Early and very early cultivars accumulated high numbers of degree days.day-1, in periods of relatively good water availability, with high exposure to solar radiation. Late cultivars accumulated less degree days.day-1 and were exposed to lower amounts of daily solar radiation and longer periods of water scarcity. Regarding the fruit ripening phase, cultivars were principally distinguished by degree days and solar radiation on a daily basis. Two of the coffee cultivars were classified or confirmed as early and very early and another three as late and very late. One cultivar, Siriema, displayed an interesting conjugation of early and intermediate characteristics.

Correction to: Arabica coffee fruits phenology assessed through degree days, precipitation, and solar radiation exposure on a daily basis.

The article was published with an erroneous rendering of Table 1. The correct rendering of this table is provided below. The original article has been corrected.

Orofacial antinociceptive effect of sulphated polysaccharide from the marine algae Hypnea pseudomusciformis in rodents.

This study aimed to evaluate the antinociceptive effect of sulphated polysaccharide from the marine algae Hypnea pseudomusciformis (PLS) using rodent models of orofacial pain. Acute pain was induced by formalin, capsaicin, cinnamaldehyde, acidified saline or glutamate (cutaneous modes) and hypertonic saline (corneal model). In one experiment, animals were pretreated with ruthenium red, glibenclamide, naloxone, L-NAME, methylene blue or ketamine to investigate the mechanism of antinociception. In another experiment, animals pretreated with PLS or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to craniofacial pain induced by mustard oil. Motor activity was evaluated with the open-field test. Cytotoxicity and antioxidant activities were also assessed. Pre-treatment with PLS significantly reduced nociceptive behavior associated with acute pain. Antinociception was effectively reduced, but not inhibited, by ruthenium red and ketamine. L-NAME and glibenclamide enhanced the PLS effect. PLS antinociception was resistant to methylene blue, naloxone and heating. PLS presented no cytotoxicity or antioxidant properties. Our results confirm the potential pharmacological relevance of PLS as an inhibitor of orofacial nociception in acute pain probably mediated by glutamatergic, nitrergic, TRPs and K + ATP pathways.

Performance Assessment of Treponemal and Nontreponemal Tests for the Diagnosis of Acquired Syphilis.

There are a variety of nontreponemal test (NTT) and treponemal test (TT) kits for the serologic diagnosis of syphilis. Because of the complexity of the infection (multiple clinical stages) and the different antigens used in these kits, a systematic evaluation of the accuracy of the currently available commercial tests is warranted. Our objective was to evaluate the performance of commercially available tests for the diagnosis of syphilis infection. In this study, we analyzed one NTT (Venereal Disease Research Laboratory [VDRL] test, Wiener Laboratories, Rosario, Argentina) and two TTs (fluorescent treponemal antibody absorption [FTA-ABS] test, Euroimmun, Lübeck, Germany, and syphilis recombinant ELISA v. 4.0 test [ELISA], Wiener Laboratories, Rosario, Argentina) using a panel of 187 samples, including serum samples from 31 individuals with primary syphilis, 77 with secondary syphilis, and 79 with latent syphilis. An additional 192 samples from uninfected individuals and 323 serum samples from individuals with other diseases were included. The sensitivities of the VDRL, ELISA, and FTA-ABS tests were 97.9%, 100%, and 96.3%, respectively. The VDRL and ELISA tests showed a specificity of 100%, and the FTA-ABS test showed a specificity of 99.5%. Accuracy was 98.9% for the VDRL test, 100% for the ELISA, and 97.9% for the FTA-ABS test. For primary, secondary, and latent syphilis, the ELISA achieved a diagnostic performance of 100%, whereas the sensitivity for the VDRL and FTA-ABS tests ranged from 96.8% to 98.7% and 93.7% to 98.7%, respectively. No difference was observed when the tests were used as traditional or reverse algorithms. In general, all three tests are able to discriminate positive and negative samples for syphilis, regardless of the diagnostic algorithm.

Evaluating the diagnostic accuracy of TpN17 and TmpA recombinant proteins in syphilis detection: a phase II study.

Syphilis is a sexually transmitted infection (STI) caused by the spiral bacterium Treponema pallidum. Diagnosis is based on epidemiology, clinical and serology, but serodiagnosis is challenging because distinct clinical forms of the infection may influence serological performance. Several recombinant Treponema pallidum-proteins have already been tested for syphilis diagnosis and they are critical to achieve high accuracy in serological testing. A total of 647 samples were included in the study: 180 T. pallidum-positive samples, 191 T. pallidum-negative samples and 276 sera from individuals infected with unrelated diseases. The diagnostic potential was validated by analysis of ROC curves. For the indirect ELISA, TpN17 (100%) and TmpA (99%) showed excellent AUC values. Sensitivity values were 97.2% for TpN17 and 90.6% for TmpA, while specificity was 100% for both molecules. According to the clinical phase, TmpA ranged from 84% to 97%, with the highest value for secondary syphilis. TpN17 was 100% sensitive for the primary and secondary stages and 93.2% for recent latent syphilis. All clinical phases achieved 100% specificity. Accuracy values showed that TmpA (> 95%) and TpN17 (> 98%) presented high diagnostic accuracy for all clinical stages of syphilis. Cross-reactivity was only observed in one sample positive for Chagas disease (1.5%), when TpN17 was evaluated. On the other hand, TmpA showed reactivity for two samples positive for Chagas disease (3.1%), one sample positive for HBV (1.25%), two samples positive for HIV (9.5%) and one sample positive for HTLV (1.6%). The TmpA antigen's performance was evaluated in multiple studies for syphilis diagnosis, corroborating our findings. However, TpN17 sensitivity values have ranged in other studies. According to clinical stages of the infection, our findings obtained close performance values.

Post-therapeutic cure criterion in chronic Chagas disease using Trypanosoma cruzi chimeric proteins.

Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi Chagas, 1909. Causative treatment can be achieved with two drugs: benznidazole or Nifurtimox. There are some gaps that hinder progress in eradicating the disease. There is no test that can efficiently assess cure control after treatment. Currently, the decline in anti-T. cruzi antibody titres is assessed with conventional serological tests, which can take years. However, the search for new markers of cure must continue to fill this gap. The present study aimed to evaluate the decline in serological titres using chimeric proteins after treatment with benznidazole in chronic patients diagnosed with CD. It was a prospective cross-sectional cohort study between 2000 and 2004 of T. cruzi-positive participants from the Añatuya region (Argentina) treated with benznidazole. Serum samples from ten patients were collected before treatment (day zero) and after the end of treatment (2, 3, 6, 12, 24 and 36 months). For the detection of anti-T. cruzi antibodies, an indirect ELISA was performed using two chimeric recombinant proteins (IBMP-8.1 and IBMP-8.4) as antigens. The changes in reactivity index within the groups before and after treatment were evaluated using the Friedman test. All participants experienced a decrease in serological titres after treatment with benznidazole, especially IBMP-8.1. However, due to the small number of samples and the short follow-up period, it is premature to conclude that this molecule serves as a criterion for sustained cure. Further studies are needed to validate tests based on these or other biomarkers to demonstrate parasitological cure.

Comparison of Four Chimeric Antigens and Commercial Serological Assays for the Diagnosis of Trypanosoma cruzi Infection.

Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, is a significant public health issue particularly in Latin America, affecting millions worldwide. Diagnosis is a challenge owing to the genetic diversity of T. cruzi and the complexities involved in selecting antigens for the detection of anti-T. cruzi antibodies. This study evaluated four chimeric recombinant antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) designed to enhance diagnostic accuracy by addressing assay variability. We compared the diagnostic performance of these chimeric antigens using indirect ELISA as a diagnostic platform, with three commercial serological assays in Brazil, analyzing 100 serum samples from individuals with confirmed CD and 86 from non-infected controls. The results revealed that all assays and antigens demonstrated an area under the receiver operating characteristic curve of 100%, signifying their exceptional ability to distinguish between CD-positive and CD-negative samples. Notably, the chimeric antigens achieved 100% sensitivity, specificity, accuracy, and kappa index, equaling or surpassing the commercial assays. This research highlights the efficacy of IBMP chimeric antigens as reliable diagnostic tools for CD, suggesting their potential integration into commercial diagnostic platforms to enhance the accuracy and reliability of CD detection.

Evaluation of chimeric recombinant antigens for the serodiagnosis of Trypanosoma cruzi in dogs: a promising tool for Chagas disease surveillance.

BACKGROUND: Chagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA). METHODS: We examined 663 canine serum samples, employing indirect ELISA with the chimeric antigens. LCA was utilized to establish a latent variable as a gold standard for T. cruzi infection, revealing distinct response patterns for each antigen. RESULTS: The IBMP (Portuguese acronym for the Molecular Biology Institute of Paraná) antigens achieved area under the ROC curve (AUC) values ranging from 90.9% to 97.3%. The highest sensitivity was attributed to IBMP-8.2 (89.8%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved 73.5%, 79.6%, and 85.7%, respectively. The highest specificity was observed for IBMP-8.4 (98.6%), followed by IBMP-8.2, IBMP-8.3, and IBMP-8.1 with specificities of 98.3%, 94.4%, and 92.7%, respectively. Predictive values varied according to prevalence, indicating higher effectiveness in endemic settings. CONCLUSIONS: Our findings underscore the remarkable diagnostic performance of IBMP-8.2 and IBMP-8.4 for the serodiagnosis of Trypanosoma cruzi in dogs, representing a promising tool for the diagnosis of CD in dogs. These chimeric recombinant antigens may not only enhance CD surveillance strategies but also hold broader implications for public health, contributing to the global fight against this neglected tropical disease.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Positron Emission Tomography-Derived Metrics Predict the Probability of Local Relapse After Oligometastasis-Directed Ablative Radiation Therapy.

PURPOSE: Early positron emission tomography-derived metrics post-oligometastasis radioablation may predict impending local relapses (LRs), providing a basis for a timely ablation. METHODS AND MATERIALS: Positron emission tomography data of 623 lesions treated with either 24 Gy single-dose radiation therapy (SDRT) (n = 475) or 3 ×  9 Gy stereotactic body radiation therapy (SBRT) (n = 148) were analyzed in a training data set (n = 246) to obtain optimal cutoffs for pretreatment maximum standardized uptake value (SUVmax) and its 3-month posttreatment decline (ΔSUVmax) in predicting LR risk, validated in a data set unseen to testing (n = 377). RESULTS: At a median of 21.7 months, 91 lesions developed LRs: 39 of 475 (8.2%) after SDRT and 52 of 148 (35.1%) after SBRT. The optimal cutoff values were 12 for SUVmax and -75% for ΔSUVmax. Bivariate SUVmax/ΔSUVmax permutations rendered a 3-tiered LR risk stratification of dual-favorable (low risk), 1 adverse (intermediate risk) and dual-adverse (high risk). Actuarial 5-year local relapse-free survival rates were 93.9% versus 89.6% versus 57.1% (P < .0001) and 76.1% versus 48.3% versus 8.2% (P < .0001) for SDRT and SBRT, respectively. The SBRT area under the ROC curve was 0.71 (95% CI, 0.61-0.79) and the high-risk subgroup yielded a 76.5% true positive LR prediction rate. CONCLUSIONS: The SBRT dual-adverse SUVmax/ΔSUVmax category LR prediction power provides a basis for prospective studies testing whether a timely ablation of impending LRs affects oligometastasis outcomes.

Technological advances in the serological diagnosis of Chagas disease in dogs and cats: a systematic review.

BACKGROUND: Chagas disease (CD) is caused by Trypanosoma cruzi, which is transmitted mainly through the feces/urine of infected triatomine bugs. The acute phase lasts 2-3 months and is characterized by high parasitemia and nonspecific symptoms, whereas the lifelong chronic phase features symptoms affecting the heart and/or digestive tract occurring in 30-40% of infected individuals. As in humans, cardiac abnormalities are observed in T. cruzi-infected dogs and cats. We reviewed the technological advances in the serological diagnosis of CD in dogs and cats. METHODS: A review of the published literature during the last 54 years (1968-2022) on the epidemiology, clinical features, diagnosis, treatment and prevention of CD in dogs and cats was conducted. RESULTS: Using predefined eligibility criteria for a search of the published literature, we retrieved and screened 436 publications. Of these, 84 original studies were considered for inclusion in this review. Dogs and cats are considered as sentinels, potentially indicating an active T. cruzi transmission and thus the risk for human infection. Although dogs and cats are reputed to be important for maintaining the T. cruzi domestic transmission cycle, there are no commercial tests to detect past or active infections in these animals. Most published research on CD in dogs and cats have used in-house serological tests prepared with native and/or full-length recombinant antigens, resulting in variable diagnostic performance. In recent years, chimeric antigens have been used to improve the diagnosis of chronic CD in humans with encouraging results. Some of them have high performance values (> 95%) and extremely low cross-reactivity rates for Leishmania spp., especially the antigens IBMP-8.1 to IBMP-8.4. The diagnostic performance of IBMP antigens was also investigated in dogs, showing high diagnostic performance with negligible cross-reactivity with anti-Leishmania infantum antibodies. CONCLUSIONS: The development of a commercial immunodiagnostic tool to identify past or active T. cruzi infections in dogs and cats is urgently needed. The use of chimeric recombinant T. cruzi antigens may help to fill this gap and is discussed in this review.