The Role of Transplacental Infection in Leptospira spp. Epidemiology in Cattle in Caatinga Biome, Brazil.

Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic impact on livestock. This study aims to investigate the importance of genital and transplacental infection in the epidemiology of leptospirosis in cows maintained in Caatinga biome conditions, Northeastern Brazil, as well as reporting organs colonized by Leptospira spp. in embryos and fetuses. Blood, urinary tract (urine, bladder, and kidney), and reproductive tract (vaginal fluid, uterus, uterine tube, ovary, and placenta) samples were collected from 15 slaughtered pregnant cows. Two embryos and 13 fetuses were sampled. Central nervous system and choroid ovoid samples were collected from embryos. Blood, central nervous system, lung, peritoneal liquid, abomasal content, liver, spleen, urine, bladder, kidney, and reproductive system samples were collected from fetuses. Diagnostic methods included the microscopic agglutination test (MAT) using a collection of 24 serovars belonging to 17 different pathogenic serogroups of five species as antigens, as well as polymerase chain reaction (PCR). Anti-Leptospira spp. antibodies were found in 9 cows (60%), while 13 cows (86.67%) had at least one organ or urine with leptospiral DNA. No fetus was seroreactive. Among the embryos and fetuses, 13 (86.67%) presented leptospiral DNA, proving a high frequency of transplacental infection (100%). For cows, the most frequent biological materials regarding Leptospira spp. DNA detection were placenta (13 out of 15 samples; 86.7%), uterus (10 out of 15 samples; 66.7%), and vaginal fluid (5 out of 15 samples; 33.3%), while, for fetuses/embryos, the most frequent PCR-positive samples were choroid ovoid (1/2; 50%), spleen (6/13; 46.2%), kidney (5/13; 38.5%), and central nervous system (5/15; 33.3%). Sequenced samples based on the LipL32 gene presented 99% similarity with L. borgpetersenii. The results indicate that transplacental infection is an efficient way of spreading Leptospira spp. in cows maintained in Caatinga biome conditions. Therefore, prevention and control strategies must include actions that interrupt transmission through this alternative route.

Incorporating versus coating antimicrobials for polymethyl methacrylate: A systematic review.

STATEMENT OF PROBLEM: Incorporating and coating with antimicrobials are techniques that can confer antimicrobial action on polymethyl methacrylate (PMMA) denture bases, which can accumulate microorganisms and promote oral and systemic disease. PURPOSE: The purpose of this systematic review was to answer the question: "Do techniques for incorporating and coating antimicrobial agents in PMMA promote antimicrobial action?" MATERIAL AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist guidelines were followed, and the SCOPUS, PubMed/Medline, EMBASE, and Science Direct databases searched. The studies were selected in 2 stages, reading the titles and abstracts and then reading the selected studies in full. The risk of bias was analyzed by adapting the quasi-experimental studies tool by the Joanna Briggs Institute (JBI). RESULTS: A total of 970 articles were found in the databases; 71 were duplicates and, after reading the abstracts, 38 were selected for full reading. From these, 6 were excluded because they did not fulfill the inclusion criteria, and 32 studies were included in this review. Autopolymerizing, heat- polymerizing, and light-polymerizing resins were evaluated, with the incorporating technique prevailing over the coating, but both techniques effectively promoted antimicrobial activity. CONCLUSIONS: Incorporating and coating antimicrobial agents are effective methods of promoting antimicrobial activity in PMMA. Combining the 2 methods led to increased antimicrobial activity compared with each individually.

BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility.

Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1-/- macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1-/- mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection.

The heme oxygenase-1 metalloporphyrin inhibitor stannsoporfin enhances the bactericidal activity of a novel regimen for multidrug-resistant tuberculosis in a murine model.

Multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) poses significant challenges to global tuberculosis (TB) control efforts. Host-directed therapies (HDTs) offer a novel approach to TB treatment by enhancing immune-mediated clearance of Mtb. Prior preclinical studies found that the inhibition of heme oxygenase-1 (HO-1), an enzyme involved in heme metabolism, with tin-protoporphyrin IX (SnPP) significantly reduced mouse lung bacillary burden when co-administered with the first-line antitubercular regimen. Here, we evaluated the adjunctive HDT activity of a novel HO-1 inhibitor, stannsoporfin (SnMP), in combination with a novel MDR-TB regimen comprising a next-generation diarylquinoline, TBAJ-876 (S), pretomanid (Pa), and a new oxazolidinone, TBI-223 (O) (collectively, SPaO), in Mtb-infected BALB/c mice. After 4 weeks of treatment, SPaO + SnMP 5mg/kg reduced mean lung bacillary burden by an additional 0.69 log10 (P = 0.01) relative to SPaO alone. As early as 2 weeks post-treatment initiation, SnMP adjunctive therapy differentially altered the expression of pro-inflammatory cytokine genes and CD38, a marker of M1 macrophages. Next, we evaluated the sterilizing potential of SnMP adjunctive therapy in a mouse model of microbiological relapse. After 6 weeks of treatment, SPaO + SnMP 10mg/kg reduced lung bacterial burdens to 0.71 ± 0.23 log10 colony-forming units (CFUs), a 0.78 log-fold greater decrease in lung CFU compared to SpaO alone (P = 0.005). However, adjunctive SnMP did not reduce microbiological relapse rates after 5 or 6 weeks of treatment. SnMP was well tolerated and did not significantly alter gross or histological lung pathology. SnMP is a promising HDT candidate requiring further study in combination with regimens for drug-resistant TB.

Effectiveness of deep dry needling versus manual therapy in the treatment of myofascial temporomandibular disorders: a systematic review and network meta-analysis.

BACKGROUND: Temporomandibular disorders (TMDs) are the most common cause of orofacial pain of non-dental origin, with approximately 42% of diagnoses corresponding to myofascial pain. Manual therapy and dry needling are commonly used interventions for the treatment of myofascial temporomandibular disorders. However, it is unclear whether one of them could be superior to the other. OBJECTIVES: The aim of the present systematic review and network meta-analysis was to compare the effectiveness of manual therapy and dry needling in patients with myofascial TMD. METHODS: This is a systematic review and network meta-analysis. Randomized clinical trials were searched in the databases of Pubmed, PEDro, CINAHL, Web of Science, Scopus, Cochrane, Google Academic and EMBASE. The methodological quality of studies included in this review was judged using the Physiotherapy Evidence Database (PEDro) scale. A frequentist network meta-analysis was carried out, assuming random effects, to estimate the effects of interventions for temporomandibular joint pain measured on a 10-point visual analogue scale. RESULTS: Out of 3190 records identified, 17 met the inclusion criteria for qualitative analysis and eight were included in the network meta-analysis. Indirect comparisons between dry needling and manual therapy showed no significant differences in their effects on pain reduction (Odds Ratio [95%CI]; - 0.263 [- 1.517, 0.992]). The ranking of treatments shows that manual therapy (SUCRA = 0.932) followed by deep dry needling (SUCRA = 0.775) present the highest values of estimation and can be considered the most likely to reduce pain. CONCLUSIONS: The results of the network meta-analysis should be considered with caution due to the low quality of the evidence available and the high variability of the study protocols in terms of the method of application of dry needling and manual therapy interventions. PROSPERO under identifier: (CRD42020186470).

The heme oxygenase-1 metalloporphyrin inhibitor stannsoporfin enhances the bactericidal activity of a novel regimen for multidrug-resistant tuberculosis in a murine model.

Multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) poses significant challenges to global tuberculosis (TB) control efforts. Host-directed therapies (HDT) offer a novel approach for TB treatment by enhancing immune-mediated clearance of Mtb. Prior preclinical studies found that inhibition of heme oxygenase-1 (HO-1), an enzyme involved in heme metabolism, with tin-protoporphyrin IX (SnPP) significantly reduced mouse lung bacillary burden when co-administered with the first-line antitubercular regimen. Here we evaluated the adjunctive HDT activity of a novel HO-1 inhibitor, stannsoporfin (SnMP), in combination with a novel MDR-TB regimen comprising a next-generation diarylquinoline, TBAJ-876 (S), pretomanid (Pa), and a new oxazolidinone, TBI-223 (O) (collectively, SPaO) in Mtb-infected BALB/c mice. After 4 weeks of treatment, SPaO + SnMP 5 mg/kg reduced mean lung bacillary burden by an additional 0.69 log10 (P=0.01) relative to SPaO alone. As early as 2 weeks post-treatment initiation, SnMP adjunctive therapy differentially altered the expression of pro-inflammatory cytokine genes, and CD38, a marker of M1 macrophages. Next, we evaluated the sterilizing potential of SnMP adjunctive therapy in a mouse model of microbiological relapse. After 6 weeks of treatment, SPaO + SnMP 10 mg/kg reduced lung bacterial burdens to 0.71 ± 0.23 log10 CFU, a 0.78 log-fold greater decrease in lung CFU compared to SpaO alone (P=0.005). However, adjunctive SnMP did not reduce microbiological relapse rates after 5 or 6 weeks of treatment. SnMP was well tolerated and did not significantly alter gross or histological lung pathology. SnMP is a promising HDT candidate requiring further study in combination with regimens for drug-resistant TB.

The Endogenous Retinoic Acid Receptor Pathway Is Exploited by Mycobacterium tuberculosis during Infection, Both In Vitro and In Vivo.

Retinoic acid (RA) is a fundamental vitamin A metabolite involved in regulating immune responses through the nuclear RA receptor (RAR) and retinoid X receptor. While performing experiments using THP-1 cells as a model for Mycobacterium tuberculosis infection, we observed that serum-supplemented cultures displayed high levels of baseline RAR activation in the presence of live, but not heat-killed, bacteria, suggesting that M. tuberculosis robustly induces the endogenous RAR pathway. Using in vitro and in vivo models, we have further explored the role of endogenous RAR activity in M. tuberculosis infection through pharmacological inhibition of RARs. We found that M. tuberculosis induces classical RA response element genes such as CD38 and DHRS3 in both THP-1 cells and human primary CD14+ monocytes via a RAR-dependent pathway. M. tuberculosis-stimulated RAR activation was observed with conditioned media and required nonproteinaceous factor(s) present in FBS. Importantly, RAR blockade by (4-[(E)-2-[5,5-dimethyl-8-(2-phenylethynyl)-6H-naphthalen-2-yl]ethenyl]benzoic acid), a specific pan-RAR inverse agonist, in a low-dose murine model of tuberculosis significantly reduced SIGLEC-F+CD64+CD11c+high alveolar macrophages in the lungs, which correlated with 2× reduction in tissue mycobacterial burden. These results suggest that the endogenous RAR activation axis contributes to M. tuberculosis infection both in vitro and in vivo and reveal an opportunity for further investigation of new antituberculosis therapies.

Strong Evidence of the Role of Donkeys in the Epidemiology of Leptospira spp. in Semiarid Conditions.

Donkeys (Equus asinus) are historically known for their close relationship to humanity, which raises the need to study zoonotic diseases that affect them. In this perspective, leptospirosis stands out as a disease with an economic and public health impact, and its occurrence is facilitated in times of higher rainfall indexes, especially in large urban centers. In view of the scarcity of information about leptospirosis in donkeys, the objective of this study was to detect the presence of Leptospira spp. and anti-leptospiral antibodies in donkeys rescued by a zoonosis center located in the Caatiga biome, Brazilian semiarid region. Overall, 30 donkeys of both sexes, aged between 4 months and 15 years, were used, from which 64 serum samples were collected and submitted to the microscopic agglutination test (MAT). In addition, 64 samples of urine, vaginal and preputial fluid, in duplicates, were subjected to the polymerase chain reaction (PCR) and microbiological. Sixteen (53.3%) animals tested positive in at least one diagnostic test, 12 (40%) of which were positive at MAT and seven (23.3%) in the molecular and bacteriological detection (urine, vaginal, and preputial fluid samples). This is the first report identifying donkeys infected with Leptospira spp. by molecular and bacteriological diagnosis in Brazil, and the first in the world to detect this agent in their genital fluids. The study also shows that donkeys are commonly exposed to leptospires in the Caatinga biome, and this constitutes a One Health-based concern, demonstrating the importance of broad studies where large numbers of humans and animals coexist when investigating zoonotic infections and when planning and implementing control measures for donkeys-associated leptospirosis.

Sandpaper: Efficient Medium for Analysis of Polishable Solid Samples by Ambient Mass Spectrometry.

In this paper, we employed sandpaper as an efficient medium to analyze polishable solid samples. As proof of principle, the surfaces of coffee beans were sanded with pieces of sandpaper cut into a triangular shape. The triangle was placed in front of the mass spectrometer inlet, and methanol was dropped on its surface. After a high-voltage application, the fingerprints of the coffee beans (n = 100) were achieved in the positive and negative ion modes in an identical procedure employed for paper spray mass spectrometry (PS-MS) analysis. The new methodology, named sandpaper spray mass spectrometry (SPS-MS), allowed for identifying many compounds in coffee beans, mainly caffeine, sugars, and carboxylic acids, among other molecules. The new technique shows advantages over PS-MS in analyzing polishable solid samples. Furthermore, compared to the direct analysis of tissues such as leaves, grains, and seeds, in which the pieces must be cut in a triangular shape (a difficult task depending on the samples' hardness), the SPS-MS technique is much more straightforward. Finally, SPS-MS can be potentially applied to analyze other hard surfaces such as wood, plastic, and assorted crop grains.

Accuracy between 2D Photography and Dual-Structured Light 3D Facial Scanner for Facial Anthropometry: A Clinical Study.

(1) Background: Facial scanners are used in different fields of dentistry to digitalize the soft tissues of the patient's face. The development of technology has allowed the patient to have a 3-dimensional virtual representation, facilitating facial integration in the diagnosis and treatment plan. However, the accuracy of the facial scanner and the obtaining of better results with respect to the manual or two-dimensional (2D) method are questionable. The objective of this clinical trial was to evaluate the usefulness and accuracy of the 3D method (a dual-structured light facial scanner) and compare it with the 2D method (photography) to obtain facial analysis in the maximum intercuspation position and smile position. (2) Methods: A total of 60 participants were included, and nine facial landmarks and five interlandmarks distances were determined by two independent calibrated operators for each participant. All measurements were made using three methods: the manual method (manual measurement), the 2D method (photography), and the 3D method (facial scanner). All clinical and lighting conditions, as well as the specific parameters of each method, were standardized and controlled. The facial interlandmark distances were made by using a digital caliper, a 2D software program (Adobe Photoshop, version 21.0.2), and a 3D software program (Meshlab, version 2020.12), respectively. The data were analyzed by SPSS statistical software. The Kolmogorov-Smirnov test revealed that trueness and precision values were normally distributed (p > 0.05), so a Student's t-test was employed. (3) Results: Statistically significant differences (p ≤ 0.01) were observed in all interlandmark measurements in the 2D group (photography) to compare with the manual group. The 2D method obtained a mean accuracy value of 2.09 (±3.38) and 2.494 (±3.67) in maximum intercuspation and smile, respectively. On the other hand, the 3D method (facial scanner) obtained a mean accuracy value of 0.61 (±1.65) and 0.28 (±2.03) in maximum intercuspation and smile, respectively. There were no statistically significant differences with the manual method. (4) Conclusions: The employed technique demonstrated that it influences the accuracy of facial records. The 3D method reported acceptable accuracy values, while the 2D method showed discrepancies over the clinically acceptable limits.

Association of hemostasis and inflammation biomarkers with outcomes in acute coronary syndromes.

Plaque rupture triggers a prothrombotic response that is counterbalanced by a fibrinolytic response. d -dimer serves as a marker of both processes. Inflammatory mediators are also released, evidenced with the rise of high-sensitive C reactive protein (hsCRP). Current evidence with these biomarkers has shown conflicting results. Determine an association between d -dimer and hsCRP within hospital and 1-year mortality in patients with acute coronary syndromes. In total, 127 patients were included. In-hospital mortality was 5.7%, and 1-year all-cause and cardiovascular mortality were 14.6 and 9.7%, respectively. The median of admission d -dimer for patients who died during hospital stay was higher than those who survived [4.59 (interquartile ranges (IQR) 1.94-6.05 µg/ml fibrinogen equivalent units (FEU)) vs. 0.56 (IQR 0.31-1.12 µg/ml FEU), P  = 0.001]. At 1-year follow-up, the median of admission d -dimer for patients who died was significantly higher than those who survived: 1.55 (IQR 0.91-5.08 µg/ml FEU) vs. 0.53 (IQR 0.29-0.90 µg/ml FEU), P  < 0.001. Positive d -dimer vs. negative d -dimer at admission analysis evidenced that almost 25% of the positive patients were dead at 1-year follow-up (22.4 vs. 2.4% negative d -dimer, P  = 0.011). Multivariate logistic regression analysis showed that d -dimer has an independent association with 1-year mortality [odds ratio 1.06 (95% confidence interval 1.02-1.10), P  = 0.006]. Positive significative correlations between d -dimer and hsCRP levels ( R  = 0.56, P  < 0.001) were found. High levels of admission d -dimer were strongly associated with in-hospital and 1-year mortality. Significant correlations with hsCRP could explain the inflammatory nature that led to poorer outcomes. d -dimer could be useful in risk stratification in acute coronary syndromes; however, a specific threshold should be defined for this type of patient.

Bovine Leptospirosis in Caatinga Biome, Brazil: New Insights into Diagnosis and Epidemiology.

Bovine leptospirosis causes economic losses and raises public health concerns. It is possible that there are peculiarities in the epidemiology of leptospirosis in regions with a semiarid climate, such as the Caatinga biome in Brazil, where the climate is hot and dry, and the etiological agent require alternative routes of transmission. This study aimed to close knowledge gaps to the diagnosis and epidemiology of Leptospira spp. infection in cows from the Caatinga biome, Brazil. Samples of the blood, urinary tract (urine, bladder and kidney) and reproductive tract (vaginal fluid, uterus, uterine tube, ovary and placenta) were collected from 42 slaughtered cows. Diagnostic tests included were the microscopic agglutination test (MAT), polymerase chain reaction (PCR) and bacterial isolation. Anti-Leptospira spp. antibodies were found in 27 (64.3%) of the animals analyzed using MAT at a 1:50 dilution (cut-off 50), while 31 (73.8%) animals had at least one organ/fluid where the presence of Leptospira spp. DNA was identified, and 29 animals (69%) were positive at bacteriological culture. The highest sensitivity values for MAT were obtained at the cut-off point of 50. In conclusion, even under hot and dry climate conditions, it is possible that Leptospira spp. can spread through alternative routes such as venereal transmission; moreover, a cut-off of 50 is recommended for the serological diagnosis of cattle from the Caatinga biome.

Antiplasmodial activity of coumarins isolated from Polygala boliviensis: in vitro and in silico studies.

Polygala boliviensis is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. Polygala spp. have different metabolites, especially coumarins. Studies indicate that coumarins have antimalarial potential, denoting the importance of researching new active compounds from plants, since the resistance of Plasmodium strains to conventional therapy has increased. The present study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum. Coumarins were isolated from P. boliviensis by open column chromatography and identified by Nuclear Magnetic Resonance Spectroscopy. A cytotoxicity assay was carried out using MTT test, and the in vitro antiplasmodial activity was evaluated using the W2 strain. The antiplasmodial activity results found were IC50=0.171 ± 0.016 for auraptene and 0.164 ± 0.012 for poligalen; the selectivity indexes were 78.71 and 609.76, respectively. Inverse virtual screening in the BRAMMT database by OCTOPUS 1.2 was applied to coumarins to find potential P. falciparum targets and showed higher affinity energy of auraptene for purine nucleoside phosphorylase (PfPNP) and of poligalen for dihydroorotate dehydrogenase (PfDHODH). Molecular Dynamics studies (MD and MM-GBSA) approach were applied to calculate binding energies against selected P. falciparum targets and showed that all coumarins were stable at the binding site during simulations. Furthermore, energies were favorable for complexation. This is the first report of auraptene in P. boliviensis species and of in vitro antiplasmodial activity of auraptene and poligalen. In silico studies indicated that the mechanism of action of coumarins is the inhibition of PfPNP and PfDHODH.Communicated by Ramaswamy H. Sarma.

Evaluating the Quality of Rigid Optic Videolaryngoscopy Image Taken Through Dental Protection Cap and Its Feasibility as Additional Barrier Method Against COVID-19.

Videolaryngoscopy screening is essential to help assessing human larynx. The use of 70° optical fiber in association with image recording by analog or digital cameras is one of the methods adopted to perform this examination. Endoscopic exams can contaminate the equipment with several microorganisms. The pandemic caused by the new coronavirus reinforces the importance of developing efficient barrier methods to be adopted in videolaryngoscopy procedures. Although dental intraoral camera covers are a barrier method authorized by Brazilian health organs, it has not yet been used in videolaryngoscopy examinations. The aim of the current longitudinal, individualized, single-blind, prospective, self-controlled, and accurate study is to evaluate the quality of images generated through, and confidence level of, diagnosis based on videolaryngoscopy performed with intraoral dental camera equipped with disposable protection cap and connected to 70° rigid laryngoscope in vocally healthy individuals. Videolaryngoscopy examinations based on 70° rigid optics were performed in 13 euphonic and asymptomatic volunteers at an otorhinolaryngology specialist clinic; only 1 patient was excluded from the study. Images were taken with, and without, disposable intraoral dental camera protection cap; high-grade disinfection protocol was applied between examinations. Recorded videos were randomly distributed in a single-blind manner in order to be evaluated by four otorhinolaryngologists, who answered a questionnaire comprising three questions. Statistical analysis was used to compare groups - which were defined by the use, or not, of protection cap - based on Wilcoxon nonparametric test. Statistical significance was set at 5% with 95% confidence interval. There was no statistically significant difference in image quality between examinations performed with, and without, protection cap (P= 0.646) or in the diagnosis confidence level of examinations performed with, or without, the barrier method. The use of disposable protection cap on intraoral dental camera did not significantly change the quality of images taken through videolaryngoscopy performed with 70° rigid optics in vocally healthy patients.

Cell death induced by NLRP3-palmitate axis impairs pulmonary damage tolerance and aggravates immunopathology during obesity-tuberculosis comorbidity.

A low-grade and persistent inflammation, which is the hallmark of obesity, requires the participation of NLRP3 and cell death. During Mycobacterium tuberculosis infection, NLRP3 signaling is important for bacterial killing by macrophages in vitro but was shown to be dispensable for host protection in vivo. We hypothesized that during obesity-tuberculosis (TB) comorbidity, NLRP3 signaling might play a detrimental role by inducing excessive inflammation. We employed a model of high-fat-diet-induced obesity, followed by M. tuberculosis infection in C57BL/6 mice. Obese mice presented increased susceptibility to infection and pulmonary immunopathology compared to lean mice. Using treatment with NLRP3 antagonist and Nlrp3-/- mice, we showed that NLRP3 signaling promoted cell death, with no effect in bacterial loads. The levels of palmitate were higher in the lungs of obese infected mice compared to lean counterparts, and we observed that this lipid increased M. tuberculosis-induced macrophage death in vitro, which was dependent on NLRP3 and caspase-1. At the chronic phase, although lungs of obese Nlrp3-/- mice showed an indication of granuloma formation compared to obese wild-type mice, there was no difference in the bacterial load. Our findings indicate that NLRP3 may be a potential target for host-directed therapy to reduce initial and severe inflammation-mediated disease and to treat comorbidity-associated TB. © 2022 The Pathological Society of Great Britain and Ireland.

Progression From Patterns A to B in Wellens Syndrome: Electrocardiographic Progression in Wellens Syndrome.

We describe a clinical case series of 3 patients whose electrocardiogram evolved from type A Wellens syndrome to a type B. We emphasize that the diagnosis and treatment for both patterns is the same and that these findings suggest the evolution of the same disease.

Neurohumoral response and stress hyperglycemia in myocardial infarction.

Background: Hyperglycemia is associated with an increased risk for death in acute coronary syndromes. This could be related to underlying glucose metabolism abnormalities or be caused by a counter-regulatory stress response. However, there is a paucity of data on the relationship between stress hormones, hyperglycemia, and clinical outcomes in myocardial infarction. Methods: Single-center, prospective, observational study. Patients admitted to the coronary care unit with a diagnosis of myocardial infarction were included. On admission, blood samples were obtained to measure serum glucose, cortisol, and catecholamines. A second sample was obtained at 8 AM after 48 h from admission. Results: There was a mild and positive correlation between serum cortisol and glucose (Spearman's rho = 0.24, p = 0.005), and no significant correlation was found between glucose and catecholamines. A similar correlation between cortisol and glucose among diabetics and non-diabetics was observed. Significantly higher serum cortisol and glucose levels were present in patients who developed heart failure or died during hospitalization. The association between glycemia and mortality lost significance in multivariate analysis, with a significant interaction term with cortisol (p = 0.003). Conclusion: Cortisol is a key responsible for stress hyperglycemia, and its deleterious effects on the cardiovascular system could be the cause for worst outcomes associated with hyperglycemia in ACS. Further research is warranted to ascertain this relationship and to investigate potential therapeutic targets.

Risk factors associated with Leptospira sp. seroprevalence in goats in Northeast of Brazil.

Goat farming is of great importance for agriculture in Northeast of Brazil, which owns more than 90 % of the national herd, however, most studies on leptospirosis in goats in this region are local surveys with unplanned sampling. Thus, the objective of this study was to determine the factors associated with the seroprevalence of leptospirosis in goats in Northeast region of Brazil. Blood samples were collected from 4121 goats from 222 herds, belonging to the states of Ceará, Paraíba, Piauí , Rio Grande do Norte and Sergipe. Serological diagnosis was carried out using the microscopic agglutination test (MAT). In 82.9 % (95 % CI = 77.3-87.2 %) of the herds there was at least one animal seropositive for at least one of the serogroups of Leptospira sp., and 18.73 % (95 % CI = 17.5-19.9 %) of the animals were seropositive. Antibody titers ranged from 100 to 800 and the most frequent serogroups were Autumnalis (23.06 %) and Australis (20.98 %). According to the robust Poisson regression analysis, four factors were associated with seroprevalence: animal sex (female) (P = 0.040), educational level of the farmer (elementary school) (P < 0.001), contacting institution for technical support (P = 0.040) and presence of irrigation area (P = 0.002). There was a high frequency of Leptospira sp. in goats in the states of Northeast region of Brazil, and it's suggested the need for better technological and preventive assistance of herds.

GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection.

Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation-mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis.

Detection of Leptospira spp. in genitourinary tract of female goats managed in the brazilian semiarid.

Studies related to the prevalence of leptospirosis in the semiarid region showed that even during long periods of drought, the disease has a remarkable frequency in herds in the region. It is a neglected disease and the extent of its effects in the Brazilian semiarid region is not known. The dynamics of this agent is well studied in the urinary tract, however, there are not many studies regarding the genital tract in female goats. Observing this scenario, the present work aimed to diagnose Leptospira spp. in female goats kept in the Brazilian semiarid region by means of serological, molecular and isolation techniques. Blood samples, vaginal fluid, urine and fragments of organs from the genitourinary tract were collected from 40 goats destined for slaughter. Microscopic agglutination test (MAT) was used as a serological technique, with a battery of 24 serovars. The Polymerase Chain Reaction (PCR) of the vaginal fluid, urine and organ fragments was performed, as well as the bacterial growth of these same products in a selective medium. Isolation positive samples were subjected to PCR. It was observed that two (5%) animals were serologically positive for the Pyrogenes serogroup. A total of 29 (72.5%) animals were PCR positive, with DNA present in 51/160 (31.8%) samples from the genital tract and 34/120 (28.3%) from the urinary tract, with no statistical difference. For bacterial growth, 22/40 (55%) animals were positive for growth, with morphology being observed in 19/160 (11.8%) for the genital tract and 16/120 (13.3%) for the urinary tract, with no statistical difference. Two uterus samples showed 99% similarity with L. interrogans after sequencing. Thus, female goats kept under semiarid conditions were positive for Leptospira spp, with positive samples from both the urinary and genital tracts, which possible is an alternative way of adapting and maintaining the agent for severe and adverse conditions.