Indeterminate Form Research Articles

Evaluation of Four Biomarkers in Patients Chronically Infected with Trypanosoma cruzi and Their Relationship with Disease Progression.

This study evaluated four biomarkers of inflammation or fibrosis as progression indicators for heart disease in patients with Chagas disease. We compared values of these markers at the time of the first sample collection of blood (first time point) and at the time of the last collection of blood (second time point) for 103 individuals positive for Trypanosoma cruzi antibodies. They were split into two clinical groups: 52 individuals with the indeterminate form of the disease at the first time point and 51 controls that already had either cardiac involvement (N = 25) or megaviscera (megaesophagus and/or megacolon; N = 26) at that time. All individuals had an electrocardiogram performed both at the first and second time point (mean time between time points: 11 years). All samples were blind tested for galectin-3, brain natriuretic peptide (NT-proBNP), lysyl oxidase-like protein 2 (LOXL2), and troponin. Differences in concentrations between samples were analyzed using the months between samples as the covariate. This analysis showed that values for all markers, except troponin biomarkers had a significative increase at the second time point for the 91 patients without progression. A similar result was obtained for NT-proBNP and LOXL2 with sera from 12 patients that progressed with cardiac disease. The single marker that showed a significative difference between groups (P = 0.01) was galectin-3. We concluded that galectin-3 was the only marker with a prognostic value in relation to the progression or worsening of heart disease in patients with Chagas disease.

Theropod and ornithischian dinosaur track assemblages from Middle to ?Late Jurassic deposits of the Central High Atlas, Morocco

ABSTRACT Tridactyl theropod and ornithischian dinosaur tracks and trackways from Imilchil and Isli formations (Middle–?Late Jurassic, Bajocian–?) of the central High Atlas region (Morocco) are described. The Imilchil Formationconsists of brackish marine-continental deposits, and the Isli Formation is a continental red-bed succession. Considering numerous new footprint discoveries, including recently described Polyonyx sauropod trackways, tridactyl dinosaur tracks from the Imilchil-Tounfite region are revised. Dominating are theropod footprints resembling the ichnogenus Changpeipus and known from Lower-Middle Jurassic deposits of China. Other theropod ichnotaxa are Trisauropodiscus isp., cf. Wildeichnus isp.,Carmelopodus isp., Megalosauripus isp., Kayentapus isp. and an indeterminate small grallatorid. Ornithischians are represented by small indeterminate ornithischian tracks, large ornithischian footprints cf. Stegopodus isp. and a large indeterminate ornithopod form. Makers of the small theropod trackswere small coelurosaurs or basal tetanurans, larger forms belong toceratosaurs, megalosauroids, allosauroids or tyrannosauroids. Ornithischian tracks suggest dryomorphs, iguanodontians and thyreophorans as producers. Together with crocodylomorph and pterosaur tracks, invertebrate traces and plants, the Imilchil and Isli formations document a flourishing ecosystem and dinosaur habitat. Remarkable is the presence of Changpeipus theropod tracks known from abundant occurrences in East Asia. This suggests an exchange of dinosaur faunas between this region and northern Africa during the Middle Jurassic.

The Non-Trivial Zeros of The Riemann Zeta Function through Taylor Series Expansion and Incomplete Gamma Function

The Riemann zeta <img src=image/13425982_01.gif> function <img src=image/13425982_02.gif> is valid for all complex number <img src=image/13425982_03.gif>, for the line <img src=image/13425982_04.gif> = 1. Euler-Riemann found that the function equals zero for all negative even integers: −2, −4, −6, ... (commonly known as trivial zeros) has an infinite number of zeros in the critical strip of complex numbers between the lines <img src=image/13425982_04.gif> = 0 and <img src=image/13425982_04.gif> = 1. Moreover, it was well known to him that all non-trivial zeros are exhibiting symmetry with respect to the critical line <img src=image/13425982_05.gif>. As a result, Riemann conjectured that all of the non-trivial zeros are on the critical line, this hypothesis is known as the Riemann hypothesis. The Riemann zeta function plays a momentous part while analyzing the number theory and has applications in applied statistics, probability theory and Physics. The Riemann zeta function is closely related to one of the most challenging unsolved problems in mathematics (the Riemann hypothesis) which has been classified as the 8th of Hilbert's 23 problems. This function is useful in number theory for investigating the anomalous behavior of prime numbers. If this theory is proven to be correct, it means we will be able to know the sequential order of the prime numbers. Numerous approaches have been applied towards the solution of this problem, which includes both numerical and geometrical approaches, also the Taylor series of the Riemann zeta function, and the asymptotic properties of its coefficients. Despite the fact that there are around 10¹³, non-trivial zeros on the critical line, we cannot assume that the Riemann Hypothesis (RH) is necessarily true unless a lucid proof is provided. Indeed, there are differing viewpoints not only on the Riemann Hypothesis's reliability, but also on certain basic conclusions see for example [16] in which the author justifies the location of non-trivial zero subject to the simultaneous occurrence of <img src=image/13425982_06.gif>, and omitting the impact of an indeterminate form <img src=image/13425982_07.gif>, that appears in Riemann's approach. In this study, we also consider the simultaneous occurrence <img src=image/13425982_06.gif> but we adopt an element-wise approach of the Taylor series by expanding <img src=image/13425982_08.gif> for all <img src=image/13425982_09.gif> = 1, 2, 3, ... at the real parts of the non-trivial zeta zeros lying in the critical strip for <img src=image/13425982_10.gif> is a non-trivial zero of <img src=image/13425982_11.gif>, we first expand each term <img src=image/13425982_08.gif> at <img src=image/13425982_12.gif> then at <img src=image/13425982_13.gif>. Then in this sequel, we evoke the simultaneous occurrence of the non-trivial zeta function zeros<img src=image/13425982_06.gif>, on the critical strip by the means of different representations of Zeta function. Consequently, proves that Riemann Hypothesis is likely to be true.

Emission distribution for the quantas of Maxwell–Chern–Simons gauge field coupled to external current

In this paper, we have investigated the nature of emission distribution of the Maxwell–Chern–Simons (MCS) theory in [Formula: see text] dimensions. The distribution of the topologically massive quanta seems to be Poissionian in nature just like the Maxwell field theory in [Formula: see text] dimensions but with a condition, without which the distribution takes an indeterminate form when we make the coupling term approach 0.

Longitudinal Speckle Tracking Strain Abnormalities in Chagas Disease: A Systematic Review and Meta-Analysis.

Background: Chronic Chagas cardiomyopathy (CCM) is ranked among heart failure etiologies with the highest mortality rates. CCM is characterized by alterations in left ventricular function with a typical and unique pattern of myocardial involvement. Left ventricle longitudinal speckle tracking strain is emerging as an important additive method for evaluating left ventricular function and risk of future cardiovascular events. This systematic review aimed to characterize the left ventricle (LV) longitudinal strain by speckle tracking patterns in the different stages of Chagas disease, compared to healthy controls. Methods: Searches in Medline, EMBASE, and LILACS databases (from inception to 20 May 2021) were performed. Articles written in any language that assessed patients with Chagas disease and reported any measures derived from the left ventricular strain by speckle tracking were included. Two reviewers independently selected the studies, extracted the data, and assessed the quality of evidence. Standardized mean differences (SMD) were pooled using random-effects meta-analyses. Results: Of 1044 references, ten studies, including a total of 1222 participants (CCM: 477; indeterminate form: 444; healthy controls: 301), fulfilled the selection criteria and were included in the final analysis. Patients with CCM had a significantly higher mean global longitudinal strain (GLS) value than indeterminate form (IF) patients (SMD 1.253; 95% CI 0.53, 1.98. I2 = 94%), while no significant difference was observed between IF patients and healthy controls (SMD 0.197; 95% CI −0.19, 0.59. I2 = 80%). Segmental strain analyses revealed that patients with the IF form of CD had significantly worse strain values in the basal-inferoseptal (SMD 0.49; 95% CI 0.24, 0.74. I2: 24%), and mid-inferoseptal (SMD 0.28; 95% CI 0.05, 0.50. I2: 10%) segments compared to healthy controls. Conclusions: Our results suggest different levels of functional derangements in myocardial function across different stages of Chagas disease. Further research is needed to assess the prognostic role of LV longitudinal strain and other measures derived from speckle tracking in CD patients regarding progression to cardiomyopathy and clinical outcomes prediction.

Hochschild cohomology of twisted tensor products

The tensor product $$R\otimes S$$ of two algebras can have its multiplication deformed by a bicharacter to yield a twisted tensor product $$R\otimes ^t S$$ . We completely describe the Hochschild cohomology of $$R\otimes ^t S$$ in terms of the Hochschild cohomology of the components R and S, including the full Gerstenhaber algebra structure. This description generalizes a result of Bergh and Oppermann. A number of interesting classes of noncommutative algebras arise as bicharacter twisted tensor products, sometimes in non-obvious ways. The main result thereby allows us to significantly simplify various calculations in the literature, and to compute Hochschild cohomology in several new classes of examples. In particular, we fully compute the Hochschild cohomology of quantum complete intersection algebras, with any number of indeterminates. One new tool which goes into the main theorem is orbit Hochschild cohomology, which can be defined for algebras with a group action, and which satisfies twisted versions of the usual Gerstenhaber algebra axioms.

Two-dimensional strain derived parameters provide independent predictors of progression to Chagas cardiomyopathy and mortality in patients with Chagas disease.

BackgroundPatients with chronic Chagas disease (CD) cardiomyopathy have a high mortality. We evaluated if two-dimensional (2D) strain (ε) parameters provide independent predictors of progression to CD cardiomyopathy and all-cause mortality.MethodsA total of 408 patients with chronic CD (58.6% women; 53 ± 11 years; clinical forms: indeterminate 34.1%, cardiac 57.6%, digestive 1.2%, cardiodigestive 7.1%) were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on ε analyses. Primary end-point was a composite of all-cause mortality or heart transplant. Secondary end-point was CD progression defined as the occurrence of changes typical of CD in electrocardiogram, sustained ventricular tachycardia, wall motion abnormalities, or heart failure among patients with the indeterminate form at baseline. Multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the studied end-points. P values < 0.05 were considered significant.ResultsThe primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01–1.18, P = .02) and radial (HR 0.97, 95% CI 0.95–0.99, P = .007) ε, and LV torsion (HR 0.51, 95% CI 0.35–0.74, P = .0004) were independent predictors of the primary end-point. Peak LV radial ε (HR 0.96, 95% CI 0.93–0.99, P = .03) was an independent predictor of CD progression.ConclusionsTherefore, 2D ε derived parameters can be useful for CD progression and mortality prediction.

Approach for noncollinear GGA kernels in closed-shell systems

Exchange-correlation kernels in density functional theory are the second-order derivatives of the exchange-correlation functionals with respect to the density matrix. For collinear functionals, the forms of kernels are well known, and their applications in calculating responses of electrons to predict properties of molecules and materials are mature. However, kernels of noncollinear functionals in closed-shell systems, except for LDA (local density approximation), are generally unknown, at least mathematically ill-defined, suffering from the indeterminate forms of 0 divided by 0. We find that such singularities in noncollinear GGA (generalized gradient approximation) kernels can be removed by introducing a proper limit process and approaching the limit after the calculations of derivatives have been done. Following this idea, mathematically well-defined noncollinear GGA kernels for closed-shell systems emerge naturally. Theoretically, these kernels are shown to be numerically stable and spin-rotational symmetry preserved. Numerical tests on excitation energies and spectroscopy parameters present reasonable results, indicating the applicability of this methodology.

Frequency of exposure to arboviruses and characterization of Guillain Barré syndrome in a clinical cohort of patients treated at a tertiary referral center in Brasília, Federal District.

ABSTRACTBackground: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents. Methods: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed. Results: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff’s encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up. Conclusions: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.

A New Method to Study Goldbach Conjecture

This paper does not claim to prove the Goldbach conjecture, but it does provide a new way of proof (LiKe sequence); And in detailed introduces the proof process of this method: by indirect transformation, Goldbach conjecture is transformed to prove that, for any odd prime sequence (3, 5, 7, …, Pn), there must have no LiKe sequence when the terms must be less than 3 × Pn. This method only studies prime numbers and corresponding composite numbers, replaced the relationship between even numbers and indeterminate prime numbers. In order to illustrate the importance of the idea of transforming the addition problem into the multiplication problem, we take the twin prime conjecture as an example and know there must exist twin primes in the interval [3Pn, P2n]. This idea is very important for the study of Goldbach conjecture and twin prime conjecture. It’s worth further study.

The Concept of Gender and Its Acceptability as a Category of Analysis in Economics: An Islamic Perspective

Changes in the understanding of gender are making it complicated to use gender as a category of analysis. Previously, it was generally accepted that gender is a binary category, comprising of male and female, based on clear biological distinction. Then came the idea that gender is a sociocultural construct. More recently, gender is said to be based on each person’s personal conception of himself or herself. These novel ideas have detached the meaning of gender from its biological foundation and have consequently made the concept of gender ambiguous and subjective, with theoretically infinite possible interpretations that can formulate an indeterminate number of genders. Such arbitrariness is unsuitable for scientific analysis. Accordingly, mainstream economists, in their aspiration to be scientific, have largely ignored these semantic developments and have continued to use the biologically defined binary categorisation of gender, presumably because of its practicality when used in economic analysis. From an Islamic perspective, economists are right to use such definition of gender, not because it is practical to do so, but because it conforms to reality and truth (ḥaqq) as revealed by religion. This article discusses these ideas as well as their history and interactions to show that from an Islamic perspective the number of genders is not indeterminate, nor is gender only practically binary, but it is really and truly binary in line with the worldview of Islam.

Extracellular Vesicles: Potential Role in Remote Signaling and Inflammation in Trypanosoma cruzi-Triggered Disease.

Extracellular vesicles (EVs) act as cell communicators and immune response modulators and may be employed as disease biomarkers and drug delivery systems. In infectious diseases, EVs can be released by the pathogen itself or by the host cells (infected or uninfected), potentially impacting the outcome of the immune response and pathological processes. Chagas disease (CD) is caused by infection by the protozoan Trypanosoma cruzi and is the main cause of heart failure in endemic areas. This illness attracted worldwide attention due to the presence of symptomatic seropositive subjects in North America, Asia, Oceania, and Europe. In the acute phase of infection, nonspecific signs, and symptoms contribute to miss diagnosis and early etiological treatment. In this phase, the immune response is crucial for parasite control; however, parasite persistence, dysregulated immune response, and intrinsic tissue factors may contribute to the pathogenesis of chronic CD. Most seropositive subjects remain in the indeterminate chronic form, and from 30 to 40% of the subjects develop cardiac, digestive, or cardio-digestive manifestations. Identification of EVs containing T. cruzi antigens suggests that these vesicles may target host cells and regulate cellular processes and the immune response by molecular mechanisms that remain to be determined. Parasite-released EVs modulate the host-parasite interplay, stimulate intracellular parasite differentiation and survival, and promote a regulatory cytokine profile in experimental models of CD. EVs derived from the parasite-cell interaction inhibit complement-mediated parasite lysis, allowing evasion. EVs released by T. cruzi-infected cells also regulate surrounding cells, maintaining a proinflammatory profile. After a brief review of the basic features of EVs, the present study focuses on potential participation of T. cruzi-secreted EVs in cell infection and persistence of low-grade parasite load in the chronic phase of infection. We also discuss the role of EVs in shaping the host immune response and in pathogenesis and progression of CD.

Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Soluble TNF receptors (sTNFR1 and sTNFR2) are natural endogenous inhibitors of TNF and are elevated in inflammatory, autoimmune, and chronic degenerative diseases. In Chagas disease, pleiotropic cytokine TNF is considered key in immunopathology. Thus, we aimed to evaluate the levels of TNF, sTNFR1, and sTNFR2 in the serum of patients with chronic Chagas disease. TNF and its soluble receptors were quantified using Cytometric Bead Array in the serum of 132 patients, of which 51 had the indeterminate form (IND), 39 the mild cardiac form (CARD 1), 42 the severe cardiac form (CARD 2), and 20 non-infected individuals (NI). The results indicate that the soluble receptors may regulate TNF in Chagas disease, as their leves were higher in T. cruzi-infected individuals when compared to non-infected individuals. We found a moderate negative correlation between sTNFR1 and TNF in individuals with the IND form, suggesting a relationship with non-progression to more severe forms, such as heart disease. sTNFR1 and sTNFR2 were increased in all clinical forms, but with a moderate positive correlation in more severe patients (r = 0.50 and p = 0.0005). TNF levels showed no statistical differences in the groups of patients. These findings suggest the importance of the endogenous balance of the levels of soluble TNF receptors in the protection and balance in patients with chronic Chagas disease, besides revealing the immunological complexity in chronic T. cruzi-infected individuals.

SLL1-ZH Regulates Spikelets Architecture and Grain Yield in Rice

The spikelet developmental processes that control structure and floral organ identity play critical roles in rice grain yield formation. In this study, we characterized a novel rice mutant, SLL1-ZH, which exhibits a variety of defective agronomic characters, including semi-dwarf, rolling leaf, deformed panicles, and reduced grains production. Morphological analysis also revealed that the SLL1-ZH mutant shows numerous defects of floral organs, such as cracked glumes, hooked and thin lemmas, shrunken but thickened paleas, an indeterminate number of stamens and stigmas, and heterotopic ovaries. Map-based cloning identified a single nucleotide substitution (C to G) in the first exon of LOC_Os09g23200 that is responsible for the SLL1-ZH phenotype. In addition, qPCR analysis showed a significant change in the relative expression of SLL1-ZH in the mutant during inflorescence differentiation and in the different floral organs. Transcription of rice floral organ development-related factors also changed significantly in the mutant. Therefore, our results suggested that SLL1-ZH plays a great role in plant growth, spikelet development, and grain yield in rice.

Distinct CD4-CD8- (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease.

CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form—IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.

Physical Exercise Promotes a Reduction in Cardiac Fibrosis in the Chronic Indeterminate Form of Experimental Chagas Disease.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease and a health problem in Latin America. Etiological treatment has limited effectiveness in chronic CD; thus, new therapeutic strategies are required. The practice of physical exercises has been widely advocated to improve the quality of life of CD patients. The most frequent clinical CD manifestation is the chronic indeterminate form (CIF), and the effect of physical exercises on disease progression remains unknown. Here, in a CIF model, we aimed to evaluate the effect of physical exercises on cardiac histological, parasitological, mitochondrial, and oxidative metabolism, electro and echocardiographic profiles, and immunological features. To establish a CIF model, BALB/c and C57BL/6 mice were infected with 100 and 500 trypomastigotes of the Y T. cruzi strain. At 120 days postinfection (dpi), all mouse groups showed normal PR and corrected QT intervals and QRS complexes. Compared to BALB/c mice, C57BL/6 mice showed a lower parasitemia peak, mortality rate, and less intense myocarditis. Thus, C57BL/6 mice infected with 500 parasites were used for subsequent analyses. At 120 dpi, a decrease in cardiac mitochondrial oxygen consumption and an increase in reactive oxygen species (ROS) were detected. When we increased the number of analyzed mice, a reduced heart rate and slightly prolonged corrected QT intervals were detected, at 120 and 150 dpi, which were then normalized at 180 dpi, thus characterizing the CIF. Y-infected mice were subjected to an exercise program on a treadmill for 4 weeks (from 150 to 180 dpi), five times per week in a 30–60-min daily training session. At 180 dpi, no alterations were detected in cardiac mitochondrial and oxidative metabolism, which were not affected by physical exercises, although ROS production increased. At 120 and 180 dpi, comparing infected and non-infected mice, no differences were observed in the levels of plasma cytokines, indicating that a crucial biomarker of the systemic inflammatory profile was absent and not affected by exercise. Compared with sedentary mice, trained Y-infected mice showed similar parasite loads and inflammatory cells but reduced cardiac fibrosis. Therefore, our data show that physical exercises promote beneficial changes that may prevent CD progression.

Immunosuppressive CD14+/HLA-DRlow/‒ monocytes in patients with Chagas Disease

Chagas Disease (CD) is a neglected illness whose immunopathological mechanisms have not yet been plainly elucidated. The asymptomatic (indeterminate) form of CD is a long-term condition and approximately 20% to 35% of the individuals with this form evolve into one of the three chronic symptomatic clinical forms of CD, namely: cardiac, digestive or cardio-digestive (mixed). A variant of blood monocytes characterized by low expression of the HLA-DR antigen (CD14+/HLA-DRlow/‒) constitutes a subtype of myeloid-derived suppressor cells (MDSCs) whose main function is to regulate exacerbated inflammatory processes. The development of the symptomatic forms of CD can be related to the interaction between the host's immune system and the CD14+/HLA-DRlow/‒ immunosuppressive monocytes. Here, we evaluated, by flow cytometry, the absolute number and the HLA-DR antigenic density of this population of MDSCs in 57 patients with the diagnosis of CD: 34 with the symptomatic clinical forms (26 cardiac and 8 mixed) and 23 with the asymptomatic (indeterminate) form. The asymptomatic form exhibited a greater number of CD14+/HLA-DRlow/‒ monocytes and, accordingly, a low HLA-DR antigenic density, when compared to the symptomatic forms. It is possible to speculate that the predominance of CD14+/HLA-DRlow/– monocytes in the patients with the asymptomatic (indeterminate) form might have been a factor that could delay or even prevent the evolution of the asymptomatic form to the symptomatic forms of Chagas Disease.

The evolutionary relationships of the earliest known cycloneuralians and a new record from the Cambrian Fortunian of South China

The Cambrian Fortunian Kuanchuanpu Formation and coeval strata in southern Shaanxi and northern Sichuan Provinces contain phosphatic carbonate that has yielded unambiguous body fossils of cycloneuralians. To date, six genera and species as well as nine indeterminate forms have been reported, and they provided information on the earliest known cycloneuralians and ecdysozoans. Among them, an indeterminate form is critical for understanding the evolution of the Fortunian cycloneuralians, and here I formally name it as Xinliscolex intermedius n. gen. n. sp. It has a series of at least seven longitudinal spinose sclerites on the dorsal side, and sensory structures such as pores and tubules distributed randomly among the annuli. The trunk end has two pairs of bilaterally arranged caudal spines. Micro-CT analysis reveals the preservation of a pharynx with inverted introvert with internally hollow scalids, an esophagus, midgut and hindgut, and a terminal anus. The digestive tract of Xinliscolex intermedius resembles that of modern priapulids, implying that the earliest known cycloneuralians have evolved a relatively derived digestive system, and this lays a foundation for their further diversification and evolution.

Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects.

Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.

Predictors of development of cardiac and digestive disorders among patients with indeterminate chronic Chagas Disease

American trypanosomiasis (Chagas disease, CD) affects circa 7 million persons worldwide. While of those persons present the asymptomatic, indeterminate chronic form (ICF), many will eventually progress to cardiac or digestive disorders. We studied a nonconcurrent (retrospective) cohort of patients attending an outpatient CD clinic in Southeastern Brazil, who were admitted while presenting the ICF in the period from 1998 through 2018 and followed until 2019. The outcomes of interest were the progression to cardiac or digestive CD forms. We were also interested in analyzing the impact of Benznidazole therapy on the progression of the disease. Extensive review of medical charts and laboratory files was conducted, collecting data up to year 2019. Demographics (upon inclusion), body mass index, comorbidities (including the Charlson index) and use of Benznidazole were recorded. The outcomes were defined by abnormalities in those test that could not be attributed to other causes. Statistical analysis included univariate and multivariable Cox regression models. Among 379 subjects included in the study, 87 (22.9%) and 100 (26.4%) progressed to cardiac and digestive forms, respectively. In the final multivariable model, cardiac disorders were positively associated with previous coronary syndrome (Hazzard Ratio [HR], 2.42; 95% Confidence Interval [CI], 1.53-3.81) and negatively associated with Benznidazole therapy (HR, 0.26; 95%CI, 0.11-0.60). On the other hand, female gender was the only independent predictor of progression to digestive forms (HR, 1.56; 95%CI, 1.03-2.38). Our results point to the impact of comorbidities on progression do cardiac CD, with possible benefit of the use of Benznidazole.