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SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P<0·01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1·11-43·9, P<0·02). Mass vaccination (>10 000 plant employees) stopped propagation in the plant, but not in the larger community. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production.Methods: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-alpha and IL-10 levels.Results: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 +/- 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 +/- 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-gamma at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-alpha were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels.Conclusion: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the marginal and internal misfit of fixed partial denture zirconia frameworks developed from conventional impression and intraoral scanning, before and after being subjected to the thermal cycle of the covering ceramic., Methods: A three-elements fixed partial denture was prepared, molded, and poured with polyurethane. Group CI (n= 7) was impressed by the conventional technique with polyvinyl siloxane material, and the plaster models scanned on the inEosX5 bench scanner. Group DI (n=07) was scanned using the CEREC Bluecam intraoral scanner. The models and images obtained were sent to the laboratory and the frameworks were made using zirconia blocks. After this, they were subjected to the ceramic thermal cycle, simulating the ceramic application. Marginal and internal misfits of the frameworks were measured before (T1) and after (T2) thermal cycle simulation using the replica technique in an optical microscope. Statistical analysis was performed using the mixed effects of linear model tests and comparisons., Results: There were no statistical differences for axial misfit. Significant differences were found between the groups for occlusal, vertical, horizontal, and absolute misfit, where group CI had higher values than group DI (P< 0.001). At the time, there was a statistical difference only in the absolute misfit, where T1 had lower values than T2. The misfit in group CI was greater than in group DI; however, the average misfit values found are low and considered clinically acceptable., Clinical Significance: Knowing marginal and internal misfit is an important step to consolidating digital impressions in fixed partial dentures, implying a secure use of this technique., Competing Interests: The authors declared no conflict of interest. The project was funded by FORP/USP and the National Council for Scientific and Technological Development (Grant number: 1678421, 2017)., (Copyright©American Journal of Dentistry.)

Introduction: Postural balance impairment can affect the quality of life of patients with Parkinson's disease. Previous studies have described connections of the vestibular system with postural functions, suggesting a potential participation of the basal ganglia in receiving vestibular stimuli. This systematic review aims to summarize the evidence on the effectiveness of vestibular rehabilitation on postural balance in patients with Parkinson's disease., Methods: A systematic review was conducted using the electronic databases: PubMed, Embase, Scopus and PEDro. The study selection was independently conducted by two reviewers, and disagreements were evaluated by a third reviewer. The included studies had no restrictions on publication dates or languages and the last update occurred in July 2023., Results: From the 485 studies found in the searches, only 3 studies were deemed eligible for the systematic review involving a total of 130 participants. The Berg Balance Scale was described as the tool for evaluation of postural balance in all studies. The meta-analysis showed statistically significant results in favor of vestibular rehabilitation (MD = 5.35; 95% CI = 2.39, 8.31; P < 0.001), regardless of the stage of Parkinson's disease. Although the effect size was suggested as a useful functional gain, the analysis was done with caution, as it only included 3 randomized controlled trials. The risk of bias using the RoB-2 was considered as being of "some concern" in all studies. Furthermore, the quality of the evidence based on the Grading of Recommendations Assessment Development and Evaluation system, produced by pooling the included studies was considered very low., Conclusion: Compared to other interventions, vestibular rehabilitation has potential to assist the postural balance of patients with Parkinson's disease. However, the very low quality of the evidence demonstrates uncertainty about the impact of this clinical practice. More robust studies are needed to confirm the benefits of this therapy in patients with Parkinson's disease. This study was prospectively registered in PROSPERO: CRD42020210185., (© 2024. The Author(s).)

Introduction: In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression., Methods: To investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4 + and CD8 + T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure., Results: We found that the frequency of IFN-γ-producingCD4 + T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4 + T cells peaked on day 7 following the start of treatment. Although the frequency of CD4 + IL-17 + cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4 + T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4 + IL-10 + cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4 + producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8 + single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8 + single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8 + double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8 + T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels., Discussion: Our results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4 + Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8 + single-producers of IFN-γ and double producers of IFN-γ and IL-17., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 de Franca, Rodrigues, Barreto, da Cruz, Aragão-Santos, da Silva, de Jesus, Palatnik-de-Sousa, de Almeida and Corrêa.)

Purpose: This study aimed to develop and evaluate a simple, non-destructive method for assessing the misfit and passivity of implant-retained prostheses frameworks., Materials and Methods: To simulate the rehabilitation of a mandible posterior partially edentulous area using 3-unit screw-retained frameworks supported by two implants were fabricated and divided into the following five groups (n = 10 in each group): OP = one-piece framework cast in Co-Cr with the conventional method (control-group); Co-Cr frameworks sectioned and welded by laser (=LAS) or tungsten inert gas (=TIG); Co-Cr CAD-CAM = milled Co-Cr framework; Zir CAD-CAM = milled zirconia framework. The horizontal |X| and vertical |Y| misfits were measured using confocal laser scanning microscopy with one or both screws tightened. Data were analyzed by a two-way ANOVA with repeated measures and Bonferroni correction (α = 0.05)., Results: The greatest |X| misfit was observed in the OP group with both screws tightened (290 µm) and one screw tightened (388 and 340 µm). The conventional casting groups sectioned and welded by laser or TIG had lower mean values (235.35 µm, both screws tightened; and 275 µm, one screw tightened) than the OP framework. However, these values still exceeded those of the milled Co-Cr and zirconia frameworks (190 and 216 µm with both screws tightened). Across all reading conditions, every framework subjected to testing consistently maintained vertical |Y| misfit levels below the threshold of 53 µm; however, the milled frameworks exhibited higher vertical misfits than the frameworks obtained by the conventional cast method., Conclusions: The frameworks, whether cast and sectioned with laser welding or milled from Co-Cr, exhibit improved marginal misfit and enhanced passive fit when compared to other fabrication methods. Additionally, the use of confocal laser scanning microscopy is highly effective for passivity and misfit analysis., (© 2024 by the American College of Prosthodontists.)

Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53-independent quiescent state in immature hepatoma cells and in pluripotent stem cell-derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity-regulated growth arrest followed by cell maturation, mediated by activation of NF-κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long-term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study focuses on developing accurate immunoassays for diagnosing Chagas disease (CD), a challenging task due to antigenic similarities between Trypanosoma cruzi and other parasites, leading to cross-reactivity. To address this challenge, chimeric recombinant T. cruzi antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) were synthesized to enhance specificity and reduce cross-reactivity in tests. While these antigens showed minimal cross-reactivity with leishmaniasis, their performance with other trypanosomatid infections was unclear. This study aimed to assess the diagnostic potential of these IBMP antigens for detecting CD in patients with Crithidia sp. LVH-60A, a parasite linked to visceral leishmaniasis-like symptoms in Brazil. This study involved seven Crithidia sp. LVH-60A patients and three Leishmania infantum patients. The results indicated that these IBMP antigens displayed 100% sensitivity, with specificity ranging from 87.5% to 100%, and accuracy values between 90% and 100%. No cross-reactivity was observed with Crithidia sp. LVH-60A, and only one L. infantum -positive sample showed limited cross-reactivity with IBMP-8.1. This study suggests that IBMP antigens offer promising diagnostic performance, with minimal cross-reactivity in regions where T. cruzi and other trypanosomatids are prevalent. However, further research with a larger number of Crithidia sp. LVH-60A-positive samples is needed to comprehensively evaluate antigen cross-reactivity., Competing Interests: The authors declare no conflicts of interest.

Background Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases.

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1 -/- mice, which when infected with CHIKV or o'nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1 -/- and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease., (© 2023. Springer Nature Limited.)

COVID-19 is caused by SARS-CoV-2 infection and leads from asymptomatic to severe outcomes. The recurrence of the COVID-19 has been described, however, mechanisms involved remains unclear. Thus, the work aimed to investigate the role of multifunctional T cells in patients with recurrent COVID-19. We evaluated clinical characteristics, presence of anti-S1 and anti-Nucleocapsid IgG in patients' sera, and multifunctional T cells (for IFN-γ, IL-2, and TNF-α) in patients with multiple episodes of COVID-19 and controls. Data demonstrate that patients with recurrent COVID-19 have a T cell pattern predominantly related to IFN-γ production. Also, patients with COVID-19 history and absence of anti-S1 IgG had lower levels of CD4+ IFN + IL-2 + TNF + T cells independently of number of disease episodes. Complementary, vaccination changed the patterns of T cells phenotypes and induced IgG seroconversion, despite not induce higher levels of multifunctional T cells in all patients. In conclusion, the data suggest that recurrent disease is related to early-disease T cell profile and absence of anti-S1 IgG is related to lower multifunctional CD4 T cell response, what suggests possibility of new episodes of COVID-19 in these patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Visceral leishmaniasis (VL) is a neglected disease considered a serious public health problem, especially in endemic countries. Several studies have discovered monoxenous trypanosomatids ( Leptomonas and Crithidia ) in patients with VL. In different situations of leishmaniasis, investigations have examined cases of co-infection between Leishmania spp. and Crithidia spp. These coinfections have been observed in a wide range of vertebrate hosts, indicating that they are not rare. Diagnostic techniques require improvements and more robust tools to accurately detect the causative agent of VL. This study aimed to develop a real-time quantitative dye-based PCR (qPCR) assay capable of distinguishing Leishmania infantum from Crithidia -related species and to estimate the parasite load in samples of VL from humans and animals. The primer LinJ31&#95;2420 targets an exclusive phosphatase of L. infantum ; the primer Catalase&#95;LVH60-12060&#95;1F targets the catalase gene of Crithidia . Therefore, primers were designed to detect L. infantum and Crithidia sp. LVH60A (a novel trypanosomatid isolated from VL patients in Brazil), in samples related to VL. These primers were considered species-specific, based on sequence analysis using genome data retrieved from the TriTryp database and the genome assembling of Crithidia sp. LVH60A strain, in addition to experimental and clinical data presented herein. This novel qPCR assay was highly accurate in identifying and quantifying L. infantum and Crithidia sp. LVH60A in samples obtained experimentally (in vitro and in vivo) or collected from hosts (humans, dogs, cats, and vectors). Importantly, the screening of 62 cultured isolates from VL patients using these primers surprisingly revealed that 51 parasite cultures were PCR+ for Crithidia sp. In addition, qPCR assays identified the co-infection of L. infantum with Crithidia sp. LVH60A in two new VL cases in Brazil, confirming the suspicion of co-infection in a previously reported case of fatal VL. We believe that the species-specific genes targeted in this study can be helpful for the molecular diagnosis of VL, as well as for elucidating suspected co-infections with monoxenous-like trypanosomatids, which is a neglected fact of a neglected disease.

Objective: The aim of this study was to examine the impact of symptom-based screening on the prevalence and outcomes of neonatal coronavirus disease 2019 in pregnant women admitted for delivery., Methods: A retrospective observational study was conducted from June to August 2020 at Gonzaga Mota of Messejana Hospital, Fortaleza, CE, Brazil. All pregnant women were screened for coronavirus disease 2019 based on symptoms. Reverse transcription-polymerase chain reaction or immunology assays for severe acute respiratory syndrome coronavirus 2 were performed when a patient reported a symptom. All newborns of symptomatic patients were submitted for Reverse transcription-polymerase chain reaction. Newborns were divided into groups according to the Reverse transcription-polymerase chain reaction results to identify the relationship between maternal symptoms and neonatal coronavirus disease 2019., Results: A total of 55 (55/1,026, 5.4%) and 50 (50/1,026, 4.8%) pregnant women reported symptoms and had a positive confirmatory test, respectively. The most common symptom of coronavirus disease 2019 among the pregnant women with positive confirmatory test was cough (n=23, 46%). Seven newborns (7/50, 14%) of symptomatic mothers had positive Reverse transcription-polymerase chain reaction. Upon birth, no newborn had serious complications., Conclusion: Universal screening of pregnant women admitted for delivery can reduce the perinatal transmission of coronavirus disease 2019. Symptom-based screening can be an alternative for regions with a low prevalence of the disease where a better allocation of financial resources is necessary.

Leprosy reaction (LR) and physical disability (PD) are the most significant clinical complications of leprosy. Herein, we assessed the circulating serum-sTREM-1 and TNF-α levels and their genetic polymorphisms in leprosy. Serum-sTREM-1 and TNF-α levels were measured in leprosy patients (LP) before treatment ( n = 51) and from their household contacts (HHCs; n = 25). DNA samples were genotyped using TREM-1 rs2234246 and TNF-α rs1800629-SNP in 210 LPs and 168 endemic controls. The circulating sTREM-1 and TNF-α levels are higher in the multibacillary form. The ROC curve of the serum-sTREM-1 levels was able to differentiate LR from non-LR and PD from non-PD. Similarly, LPs with serum-sTREM-1 levels >210 pg/ml have 3-fold and 6-fold higher chances of presenting with LR and PD, respectively. Genotypes CC+CT of the TREM-1 were associated with leprosy. Taken together, our analyses indicated that sTREM-1 and TNF-α play an important role in the pathogenesis of leprosy and provide promising biomarkers to assist in the diagnosis of leprosy complications., Competing Interests: Authors SR and MD are employed by HDT Bio Corp. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bezerra-Santos, Bomfim, Santos, Cunha, de Moraes, Cazzaniga, Tenório, Araujo, Menezes-Silva, Magalhães, Barreto, Reed, Duthie, Lipscomb, de Almeida, de Moura and de Jesus.)

In the Americas, visceral leishmaniasis (VL) is caused by the protozoan Leishmania infantum, leading to death if not promptly diagnosed and treated. In Brazil, the disease reaches all regions, and in 2020, 1,933 VL cases were reported with 9.5% lethality. Thus, an accurate diagnosis is essential to provide the appropriate treatment. Serological VL diagnosis is based mainly on immunochromatographic tests, but their performance may vary by location, and evaluation of diagnostic alternatives is necessary. In this study, we aimed to evaluate the performance of ELISA with the scantily studied recombinant antigens, K18 and KR95, comparing their performance with the already known rK28 and rK39. Sera from parasitologically confirmed symptomatic VL patients (n = 90) and healthy endemic controls (n = 90) were submitted to ELISA with rK18 and rKR95. Sensitivity (95% CI) was, respectively, 83.3% (74.2-89.7) and 95.6% (88.8-98.6), and specificity (95% CI) was 93.3% (85.9-97.2) and 97.8% (91.8-99.9). For validation of ELISA with the recombinant antigens, we included samples from 122 VL patients and 83 healthy controls collected in three regions in Brazil (Northeast, Southeast, and Midwest). When comparing the results obtained with the VL patients' samples, significantly lower sensitivity was obtained by rK18-ELISA (88.5%, 95% CI: 81.5-93.2) compared with rK28-ELISA (95.9%, 95% CI: 90.5-98.5), but the sensitivity was similar comparing rKR95-ELISA (95.1%, 95% CI: 89.5-98.0), rK28-ELISA (95.9%, 95% CI: 90.5-98.5), and rK39-ELISA (94.3%, 95% CI: 88.4-97.4). Analyzing the specificity, it was lowest with rK18-ELISA (62.7%, 95% CI: 51.9-72.3) with 83 healthy control samples. Conversely, higher and similar specificity was obtained by rKR95-ELISA (96.4%, 95% CI: 89.5-99.2), rK28-ELISA (95.2%, 95% CI: 87.9-98.5), and rK39-ELISA (95.2%, 95% CI: 87.9-98.5). There was no difference in sensitivity and specificity across localities. Cross-reactivity assessment, performed with sera of patients diagnosed with inflammatory disorders and other infectious diseases, was 34.2% with rK18-ELISA and 3.1% with rKR95-ELISA. Based on these data, we suggest using recombinant antigen KR95 in serological assays for VL diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fujimori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case-control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants., (© 2023. The Author(s).)

This dataset is related to the article "Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection" by S.R. Maruyama, C.A. Fuzo, A.E.R. Oliveira, L.A. Rogerio, N.T. Takamiya, G. Pessenda, E.V. de Melo, A.M. da Silva, A.R. Jesus, V. Carregaro, H.I. Nakaya, R.P. Almeida and J.S. da Silva. Frontiers in Immunology, 2022. Through the reuse of raw sequencing data, we generated original dataset by performing a dual RNA-seq mapping procedure to survey the parasite transcripts found in RNA-seq samples from blood of visceral leishmaniasis patients. Diseased patients with active infection displayed the highest number of reads mapped to L. infantum genome. Even after six months later of the treatment, when the patients were considered cured, parasite reads were still detected. Parasite reads were also detected in asymptomatic individuals. The original dual RNA-seq alignment read count data provided here can be further explored to evaluate either host or parasite transcripts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer VA declared a shared affiliation with the author MR to the handling editor at the time of review., (Copyright © 2022 Magalhães, Melo, Damascena, Albuquerque, Santos, Rebouças, Bezerra, Louzada da Silva, de Oliveira, Santos, da Silva, Lipscomb, da Silva, de Jesus and de Almeida.)

Commercial Yttria-tetragonal zirconia polycrystalline (Y-TZP) was subjected to surface treatments, and the bond strength of dual resin cement to Y-TZP and failure modes were evaluated. Disks (12 mm × 2 mm), cylinders (7 mm × 3.3 mm), and bars (25 mm × 5 mm × 2 mm) were milled from Y-TZP CAD-CAM blocks, divided into seven groups, and subjected to different surface treatments; silicatization was used as control. On the basis of the literature, this study evaluated modifications with films containing SiO2 nanoparticles and silane; SiO2+ZrO2—SiO2 (50%) and ZrO2 (50%) nanoparticles, SiO2+ZrO2/Silane-SiO2 (50%) and ZrO2 (50%) nanoparticles, and silane. Specimens were analyzed by wettability (n = 3), surface free energy (n = 3), X-ray diffraction (n = 1), Fourier transform infrared spectroscopy (FTIR) (n = 1), roughness (n = 5), shear bond test (n = 10), and dynamic modulus (n = 3). Specimens treated with hydrofluoric acid—HF 40% presented significantly higher contact angle and lowest surface free energy (p < 0.05). The SiO2/Silane presented crystalline SiO2 on the surface. The surface roughness was significantly higher for groups treated with nanofilms (p < 0.05). Shear bond strength was significantly higher for silicatization, HF 40%/silicatization, SiO2/Silane, and SiO2+ZrO2/Silane groups. The proposed treatments with nanofilms had potentially good results without prejudice to the physicochemical characteristics of zirconia. Generally, groups that underwent silica surface deposition and silanization had better bond strength (p < 0.005).

Background and Aims: The Point of Care Ultrasound and Point-of-Care Ultrasound in Resource-Limited Settings are differentiated diagnostic methods using ultrasound, essential in urgent patients screening, allowing better guidance in the diagnostic process and therapeutic approach. This study intends to observe the impact of these techniques in two Basic Emergency Services (SUB) in Portugal., Methods: A longitudinal study was carried out in two remote locations in Portugal (SUB N and SUB S). Data were collected by trained radiographers in each location, and a total of 972 exams were considered. Imaging findings were documented by exam type, the exam normality and the resolution after exam. χ 2 and Cramer's V tests were performed to check significant correlations between the variables., Results: Regarding the type of echographic findings, 289 (29.7%) were considered normal, 628 (64.6%) were classified as abnormal and 55 (5.7%) were considered inconclusive. As for the type of resolution, 58% had local resolution, 24% were referred to a hospital emergency service and 18% referred to ambulatory care. Regarding the Location versus Resolution after exam versus Findings variables, it was verified a stronger statistically significant association for the exams considered "Abnormal" (Cramer's V  = 0.414; p  < 0.001). In the variables Location versus Findings versus Resolution after exam, it was verified a stronger statistical significance for "Referral to Ambulatory" (Cramer V  = 0.443; p  < 0.001) although Referral for Hospital (Cramer V  = 0.252; p  = 0.003) or Local Resolution (Cramer V  = 0.252; p  < 0.001) also had a moderate association strength., Conclusion: Ultrasonography is a useful diagnostic tool for patients screening, having an influence on patient management in remote settings. Given the limited literature in Portugal about this matter, further research and literature will be needed to support and complement the results of this study., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Spatial arrangement of distinct Amazonian environments through time and its effect on specialized biota remain poorly known, fueling long-lasting debates about drivers of biotic diversification. We address the late Quaternary sediment deposition that assembled the world's largest seasonally flooded ecosystems. Genome sequencing was used to reconstruct the demographic history of bird species specialized in either early successional vegetation or mature floodplain forests. Sediment deposition that built seasonally flooded habitats accelerated throughout the Holocene (last 11,700 years) under sea level highstand and intensification of the South American Monsoon, at the same time as global increases in atmospheric methane concentration. Bird populations adapted to seasonally flooded habitats expanded due to enlargement of Amazonian river floodplains and archipelagos. Our findings suggest that the diversification of the biota specialized in seasonally flooded habitats is coupled to sedimentary budget changes of large rivers, which rely on combined effects of sea level and rainfall variations., (© 2022. The Author(s).)

The Aptian was characterized by dramatic tectonic, oceanographic, climatic and biotic changes and its record is punctuated by Oceanic Anoxic Events (OAEs). The timing and duration of these events are still contentious, particularly the age of the Barremian-Aptian boundary. This study presents a cyclostratigraphic evaluation of a high-resolution multiproxy dataset (δ 13 C, δ 18 O, MS and ARM) from the Poggio le Guaine core. The identification of Milankovitch-band imprints allowed us to construct a 405-kyr astronomically-tuned age model that provides new constraints for the Aptian climato-chronostratigraphic framework. Based on the astronomical tuning, we propose: (i) a timespan of ~7.2 Myr for the Aptian; (ii) a timespan of ~420 kyr for the magnetic polarity Chron M0r and an age of ~120.2 Ma for the Barremian-Aptian boundary; and (iii) new age constraints on the onset and duration of Aptian OAEs and the 'cold snap'. The new framework significantly impacts the Early Cretaceous geological timescale., (© 2022. The Author(s).)

Alphaviral arthritides caused by mosquito-borne arboviruses such as chikungunya virus (CHIKV) can persist for months after the initial acute disease. Here, we investigated the contribution of interleukin-17 (IL-17), a cytokine involved in chronic autoimmune arthropathies such as rheumatoid arthritis, to the development of alphaviral arthropathy. Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease. We sought to validate these findings using a mouse model of CHIKV infection and disease using wild-type and IL-17A-deficient mice. Mice were infected with CHIKV, and joint and muscle tissues were harvested at designated time points. Tissue infiltrates were examined by immunohistochemistry, and tissue mRNA and protein expression of cytokines was assessed. Joint and muscle pathology was assessed using histology. CHIKV-infected mice lacking IL-17A showed reduced tissue inflammation and neutrophil infiltration, compared to wild-type mice. These investigations showed a role for IL-17 in the acute phase of CHIKV infection and also during the postacute disease resolution phase. IMPORTANCE CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV. The upregulation of IL-17 detected in CHIKV disease patients and the reduced disease seen in IL-17-deficient mice suggest a correlation between IL-17 signaling pathways and CHIKV-induced arthritic inflammation. With an established role in contributing to the pathogenesis of immune-mediated diseases, such as psoriatic arthritis and rheumatoid arthritis, IL-17 signaling plays an important role in alphavirus arthritides.

Visceral leishmaniasis (VL) is a vector-borne infectious disease that can be potentially fatal if left untreated. In Brazil, it is caused by Leishmania infantum parasites. Blood transcriptomics allows us to assess the molecular mechanisms involved in the immunopathological processes of several clinical conditions, namely, parasitic diseases. Here, we performed mRNA sequencing of peripheral blood from patients with visceral leishmaniasis during the active phase of the disease and six months after successful treatment, when the patients were considered clinically cured. To strengthen the study, the RNA-seq data analysis included two other non-diseased groups composed of healthy uninfected volunteers and asymptomatic individuals. We identified thousands of differentially expressed genes between VL patients and non-diseased groups. Overall, pathway analysis corroborated the importance of signaling involving interferons, chemokines, Toll-like receptors and the neutrophil response. Cellular deconvolution of gene expression profiles was able to discriminate cellular subtypes, highlighting the contribution of plasma cells and NK cells in the course of the disease. Beyond the biological processes involved in the immunopathology of VL revealed by the expression of protein coding genes (PCGs), we observed a significant participation of long noncoding RNAs (lncRNAs) in our blood transcriptome dataset. Genome-wide analysis of lncRNAs expression in VL has never been performed. lncRNAs have been considered key regulators of disease progression, mainly in cancers; however, their pattern regulation may also help to understand the complexity and heterogeneity of host immune responses elicited by L. infantum infections in humans. Among our findings, we identified lncRNAs such as IL21-AS1, MIR4435-2HG and LINC01501 and coexpressed lncRNA/mRNA pairs such as CA3-AS1/CA1, GASAL1/IFNG and LINC01127/IL1R1-IL1R2. Thus, for the first time, we present an integrated analysis of PCGs and lncRNAs by exploring the lncRNA-mRNA coexpression profile of VL to provide insights into the regulatory gene network involved in the development of this inflammatory and infectious disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maruyama, Fuzo, Oliveira, Rogerio, Takamiya, Pessenda, de Melo, da Silva, Jesus, Carregaro, Nakaya, Almeida and da Silva.)

Background: To demonstrate the value of implementation of an artificial intelligence solution in health care service, a winning project of the Massachusetts Institute of Technology Hacking Medicine Brazil competition was implemented in an urgent care service for health care professionals at Hospital das Clínicas of the Faculdade de Medicina da Universidade de São Paulo during the COVID-19 pandemic., Objective: The aim of this study was to determine the impact of implementation of the digital solution in the urgent care service, assessing the reduction of nonvalue-added activities and its effect on the nurses' time required for screening and the waiting time for patients to receive medical care., Methods: This was a single-center, comparative, prospective study designed according to the Public Health England guide "Evaluating Digital Products for Health." A total of 38,042 visits were analyzed over 18 months to determine the impact of implementing the digital solution. Medical care registration, health screening, and waiting time for medical care were compared before and after implementation of the digital solution., Results: The digital solution automated 92% of medical care registrations. The time for health screening increased by approximately 16% during the implementation and in the first 3 months after the implementation. The waiting time for medical care after automation with the digital solution was reduced by approximately 12 minutes compared with that required for visits without automation. The total time savings in the 12 months after implementation was estimated to be 2508 hours., Conclusions: The digital solution was able to reduce nonvalue-added activities, without a substantial impact on health screening, and further saved waiting time for medical care in an urgent care service in Brazil during the COVID-19 pandemic., (©Kaio Jia Bin, Adler Araujo Ribeiro Melo, José Guilherme Moraes Franco da Rocha, Renata Pivi de Almeida, Vilson Cobello Junior, Fernando Liebhart Maia, Elizabeth de Faria, Antonio José Pereira, Linamara Rizzo Battistella, Suzane Kioko Ono. Originally published in JMIR Formative Research (https://formative.jmir.org), 01.02.2022.)

In American Tegumentary Leishmaniasis production of cytokines, reactive oxygen species and nitric oxide (NO) by host macrophages normally lead to parasite death. However, some Leishmania braziliensis strains exhibit natural NO resistance. NO-resistant strains cause more lesions and are frequently more resistant to antimonial treatment than NO-susceptible ones, suggesting that NO-resistant parasites are endowed with specific mechanisms of survival and persistence. To tests this, we analyzed the effect of pro- and antioxidant molecules on the infectivity in vitro of L. braziliensis strains exhibiting polar phenotypes of resistance or susceptibility to NO. In addition, we conducted a comprehensive quantitative mass spectrometry-based proteomics analysis of those parasites. NO-resistant parasites were more infective to peritoneal macrophages, even in the presence of high levels of reactive species. Principal component analysis of protein concentration values clearly differentiated NO-resistant from NO-susceptible parasites, suggesting that there are natural intrinsic differences at molecular level among those strains. Upon NO exposure, NO-resistant parasites rapidly modulated their proteome, increasing their total protein content and glutathione (GSH) metabolism. Furthermore, NO-resistant parasites showed increased glucose analogue uptake, and increased abundance of phosphotransferase and G6PDH after nitrosative challenge, which can contribute to NADPH pool maintenance and fuel the reducing conditions for the recovery of GSH upon NO exposure. Thus, increased glucose consumption and GSH-mediated redox capability may explain the natural resistance of L. braziliensis against NO.

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 μg/ml) or egg (SEA-10 μg/ml) antigens or purified protein derivative of turberculin (PPD-10 μg/ml) or phytohemagglutinin (PHA-1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17 , IL10 , and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Franco, de Amorim, Santos, Rollemberg, de Oliveira, França, Santos, Magalhães, Cazzaniga, de Lima, Benevides, Carregaro, Silva, Brito, Fernandes, da Silva, de Almeida, Bezerra-Santos and de Jesus.)

Visceral leishmaniasis (VL) is a tropical disease endemic to Brazil. The clinical manifestations of the infection range from asymptomatic to severe. In VL, changes in lipid metabolism, such as hypocholesterolemia and hypertriglyceridemia, occur that are believed to be related to its progression and severity. This study investigated the associations between serum levels of cholesterol, triglycerides, and lipoproteins (high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein) with clinical and hematological parameters that predict severity in a case series of 83 VL patients. Severely ill patients had higher mean serum triglyceride levels than non-severely ill patients. There was a significant positive correlation between disease severity score and serum triglyceride levels, very low-density lipoprotein, international normalized ratio for prothrombin time test, total bilirubin, and age. An inverse correlation was detected between the disease severity score and mean platelet and neutrophil counts. Hypertriglyceridemia can be a prognostic indicator of severity in patients diagnosed with VL.

Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti- Leishmania -specific CD4 + T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4 + and CD8 + T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4 + TNF-α + IFN-γ + and the multifunctional CD4 + IL-2 + TNF-α + IFN-γ + , together with CD4 + TNF-α + and CD4 + IFN-γ + T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8 + IL-2 + TNF-α + IFN-γ + and CD8 + TNF-α + IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4 + and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8 Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8 High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4 + and CD8 + cytokine-secreting T cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rodrigues, Barreto, Bomfim, Gomes, Ferreira, da Cruz, Magalhães, de Jesus, Palatnik-de-Sousa, Corrêa and de Almeida.)

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are successful orthopaedic procedures with an ever-increasing demand annually worldwide, and persistent wound drainage (PWD) is a well-known complication following these procedures. Despite many definitions for PWD having been proposed, a validated description remains elusive.PWD is a risk factor for periprosthetic joint infection (PJI). PJI is a devastating complication of THA and TKA, and a leading cause of revision surgery with dramatic morbidity and mortality and a significant burden on health socioeconomics.Prevention of PJI has become an essential focus in THA and TKA. Understanding the pathophysiology, risk factors and subsequent management of PWD may aid in decreasing the rate of PJI.Risk factors of PWD can be divided into modifiable and non-modifiable patient risk factors, pharmacological and surgical risk factors. No gold standard treatment protocol to address PWD exists; however, non-operative options progressing to surgical interventions have been described.The aim of this study was to review the current literature regarding PWD and consolidate the risk factors and management strategies available. Cite this article: EFORT Open Rev 2021;6:872-880. DOI: 10.1302/2058-5241.6.200054., Competing Interests: ICMJE Conflict of interest statement: LM reports consultancy and lecture fees paid by Zimmerbiomet, and Consultancy fees also from Advanced Orthopaedics, and Implantcast, for relevant financial activities outside the submitted work. All other authors declare no conflicts of interest relevant to this work., (© 2021 The author(s).)

Functionally, cluster of differentiation 14 (CD14) is a co-receptor of the complex formed by lipopolysaccharide (LPS) and LPS-binding protein expressed on the membrane of a variety of cells. However, CD14 can be shed from the cell membrane into the circulation as soluble CD14 (sCD14) upon cell activation. Previously, our group reported that elevated sCD14 serum levels were associated with the clinical and laboratory findings in the context of visceral leishmaniasis (VL), but not in the context of LPS stimulation or bacterial infection. In the present study, we investigated the secretion dynamics of sCD14 in the context of Leishmania infantum (syn. L. chagasi) in vitro infection. Macrophages from treated VL patients and delayed-type hypersensitivity positive (DTH + ) subjects were infected with L. infantum (syn. L. chagasi) promastigotes, and the infection index was evaluated (number of amastigotes per 100 infected macrophages). Additionally, the levels of sCD14, Inteleukin (IL)10, IL-6 and tumour necrosis factor alpha (TNF-α) were measured in the culture supernatants using the Luminex assay. Interestingly, the release of sCD14 was inversely correlated with the L. infantum (syn. L. chagasi) infection index. Of note, the release of sCD14 was upregulated and downregulated in the context of infected macrophages from DTH + subjects and treated VL patients, respectively. Additionally, we also observed that the levels of sCD14 in the culture supernatants were positively correlated with the levels of TNF-α, IL-6 and IL-10. Therefore, our data suggest that macrophages from treated VL patients and DTH + subjects respond differently to L. infantum (syn. L. chagasi) infection in the context of the release of sCD14; therefore, the release of sCD14 may be associated with the outcome of VL., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Methylmalonic acidemia is a rare metabolic disorder caused by the deficient activity of l-methylmalonyl-CoA mutase or its cofactor 5-deoxyadenosylcobalamin and is characterized by accumulation of methylmalonic acid (MMA) and alternative metabolites. The brain is one of the most affected tissues and neurologic symptoms, characterized by seizures, mental retardation, psychomotor abnormalities, and coma, commonly appear in newborns. The molecular mechanisms of neuropathogenesis in methylmalonic acidemia are still poorly understood, specifically regarding the impairments in neuronal development, maturation, and differentiation. In this study, we investigated the effects of MMA in both undifferentiated and differentiated phenotypes of SH-SY5Y human neuroblastoma cells. We observed an increase in glucose consumption and reduction in respiratory parameters of both undifferentiated and differentiated cells after exposition to MMA, suggesting that differentiated cells are slightly more prone to perturbations in respiratory parameters by MMA than undifferentiated cells. Next, we performed qPCR of mature neuronal-specific gene markers and measured mitochondrial functioning to evaluate the role of MMA during differentiation. Our results showed that MMA impairs the respiratory parameters only at the late stage of differentiation and downregulates the transcriptional gene profile of mature neuronal markers neuron-specific enolase (ENO2) and synaptophysin (SYP). Altogether, our findings point out important changes observed during neuronal maturation and energetic stress vulnerability that can play a role in the neurological clinical symptoms at the newborn period and reveal important molecular mechanisms that could help the screening of targets to new approaches in the therapies of this disease.

Mastitis is a bacterial infection that affects all lactating mammals, and in dairy cattle, it leads to a reduction in their milk production and, in worse cases, it may lead to animal death. One viable therapeutic modality for overcoming bacterial resistance can be photodynamic inactivation (PDI), a therapeutic modality for bacterial infection treatment. One of the main factors that can lead to an efficient PDI process is the association of metallic nanoparticles in the close vicinity of photosensitizers, which has shown promising results due to localized surface plasmon resonance phenomena. In this work, methylene blue (MB) molecules were associated with Ag prismatic nanoplatelets (AgNPrs) to use as PDI photosensitizer against Staphylococcus aureus isolated from bubaline mastitis. The optical plasmonic activity of AgNPrs was tuned to the MB absorption region (600-700 nm) by inducing their growth into prismatic shapes by a seed-mediated procedure, using poly (sodium 4-styrene sulfonate) as the surfactant. A simulation on the plasmonic properties of the nanoprisms, applying particle size within the dimensions determined by TEM image analysis (d = 32 ± 6 nm), showed a 30 % increase of the incident field on the prismatic tips. Photodynamic results showed that the electrostatic AgNPr-MB conjugates promoted enhancement (ca. 15 %) of the reactive oxygen species production. Besides, PDI mediated by AgNPrs-MB led to the complete inactivation of the mastitis S. aureus strain after 6 min inactivation, in contrast to PDI mediated by MB, which reduced less than a 0.5 bacterial log. Thus, the results show this plasmonic enhanced photodynamic tool's potential to be applied in the inactivation of multi-resistant bacterial strains., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term., Methods: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database., Results: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p <0.0001)), and blood type A (OR 4.8 (p = 0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19  (2.4 ± 0.610; p<0.0001) and after recurrence (6.4 ± 11.34; p = 0.007).  Virus genome sequencing identified reinfection by a different isolate in one patient., Conclusions: This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode., Competing Interests: Declaration of Competing Interests All authors report there are no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate whether a common measure of sagittal pelvic torsion based on the superior iliac spines behave similarly to predictions of a rigid (non-torsioned) plane, when leg length discrepancies (LLD) are induced., Method: Twenty-four young asymptomatic participants were subjected to pelvic posture measurements that use the anterior-superior iliac spines (ASISs) and posterior-superior iliac spines (PSISs) as references, while standing on level ground and with a one-, two- and three-centimeter lifts under the left foot. A special caliper with digital inclinometers was used. The following angles were measured: angles of the right and left PSIS-to-ASIS lines; right-left relative angle (RLRA), as the angle between the right and left PSIS-to-ASIS lines, which is a traditional lateral-view measure intended to detect sagittal torsions; angle of the inter-ASISs line; angle of the inter-PSISs line; anterior-posterior relative angle (APRA), as the angle between the inter-ASISs and inter-PSISs lines. According to trigonometric predictions based on the geometry given by the lines linking the superior iliac spines (i.e. a trapezoid plane), a pure lateral tilt of the pelvis, without interinnominate sagittal motion, would change RLRA in a specific direction and would not change APRA., Results: Repeated-measures ANOVAs revealed that RLRA (p<0.001) and right and left PSIS-to-ASIS angles (p≤0.001) changed, and APRA did not change (p=0.33), as predicted., Conclusions: At least part of the sagittal torsion detected by measures that assume the PSIS-to-ASIS angles as the sagittal angles of the innominates is due to pelvic geometry and not to the occurrence of actual torsion, when LLDs are induced., (Copyright © 2021. Published by Elsevier Inc.)

Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Plasmodium vivax is the most prevalent cause of malaria outside of Africa. P. vivax biology and pathogenesis are still poorly understood. The role of one highly occurring phenotype in particular where infected reticulocytes cytoadhere to noninfected normocytes, forming rosettes, remains unknown. Here, using a range of ex vivo approaches, we showed that P. vivax rosetting rates were enhanced by plasma of infected patients and that total immunoglobulin M levels correlated with rosetting frequency. Moreover, rosetting rates were also correlated with parasitemia, IL-6 and IL-10 levels in infected patients. Transcriptomic analysis of peripheral leukocytes from P. vivax-infected patients with low or moderated rosetting rates identified differentially expressed genes related to human host phagocytosis pathway. In addition, phagocytosis assay showed that rosetting parasites were less phagocyted. Collectively, these results showed that rosette formation plays a role in host immune response by hampering leukocyte phagocytosis. Thus, these findings suggest that rosetting could be an effective P. vivax immune evasion strategy.

[This corrects the article DOI: 10.1371/journal.pone.0230610.].

Background: The development of rK39-based immunochromatographic rapid diagnostic tests represents an important advance for serodiagnosis of visceral leishmaniasis, being cheap and easy to use at the point of care (POC). Although the use of rK39 have considerably improved the sensitivity and specificity of serological tests compared with total antigens, great variability in sensitivity and specificity was reported. This study aimed at the evaluation of "Kalazar Detect™ Rapid Test, Whole Blood" (Kalazar Detect RDT) for Visceral Leishmaniasis (VL) diagnosis using oral fluid, whole blood and serum specimens collected at different endemic areas of VL of Brazil., Methodology: To evaluate Kalazar Detect RDT, oral fluid, whole blood and serum specimens from 128 VL patients, 85 healthy individuals, 22 patients with possible cross-reactivity diseases and 20 VL/aids coinfected patients were collected and assayed at the POC., Principal Findings and Conclusions: The performance of Kalazar Detect RDT in whole blood and serum was similar; however, using oral fluid, the sensitivity was low. Particularly in samples from the city of Natal, Rio Grande do Norte state in Northeastern Brazil, we observed low sensitivity, 80.0% (95% CI: 62.7-90.5), using whole blood and serum, and poor sensitivity, 43.3% (95% CI: 27.4-60.8) with oral fluid. Those values were much lower than in the other regions, where sensitivity ranged from 92.7-96.3% in whole blood and serum, and 80.0-88.9% in oral fluid. Besides, in VL/aids coinfected patients, lower sensitivity was achieved compared with VL patients. In samples from Natal, the sensitivity was 0.0% (95% CI: 0.0-49.0) and 25.0% (95% CI: 4.6-69.9), using oral fluid and serum/whole blood, respectively; in samples from the other regions, the sensitivity ranged from 40.0-63.6% and 80.0-81.8%, respectively. As for specificity, high values were observed across the fluids, 100.0% (95% CI: 96.5-100.0) in whole blood, 96.3% (95% CI: 90.8-98.5) in serum, and 95.3% (95% CI: 89.5-98.0) in oral fluid; across localities, specificity ranged from 85.7-100.0%. Serum samples sent by the collaborating centers to Instituto de Medicina Tropical (n = 250) were tested by Kalazar Detect RDT, Direct Agglutination Test, Indirect immunofluorescence assay, Enzyme-linked immunosorbent assay, and IT-Leish® RDT. The regional difference in the performance of rK39-based RDT and lower sensitivity in Leishmania/HIV coinfected patients raise concern on the routine use of these products for the diagnosis of VL., Competing Interests: The authors have declared that no competing interests exist.