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Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4 + T cell subsets remain unresolved. Here, we examine antigen-experienced CD4 + T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic T EM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with T CM /Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4 + T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4 + T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection., (© 2024. The Author(s).)

Perinatal hypoxia-ischemia (HI) is a leading cause of morbidity and mortality among newborns. Infants with HI encephalopathy may experience lasting consequences, such as depression, in adulthood. In this study, we examined depressive-like behavior, neuronal population, and markers of monoaminergic and synaptic plasticity in the prefrontal cortex (PFC) of adolescent rats subjected to a prenatal HI model. Pregnant rats underwent a surgery in which uterine and ovarian blood flow was blocked for 45 min at E18 (HI procedure). Sham-operated subjects were also generated (SH procedure). Behavioral tests were conducted on male and female pups from P41 to P43, and animals were histologically processed or dissected for western blotting at P45. We found that the HI groups consumed less sucrose in the sucrose preference test and remained immobile for longer periods in the forced swim test. Additionally, we observed a significant reduction in neuronal density and PSD95 levels in the HI group, as well as a smaller number of synaptophysin-positive cells. Our results underscore the importance of this model in investigating the effects of HI-induced injuries, as it reproduces an increase in depressive-like behavior and suggests that the HI insult affects circuits involved in mood modulation., Competing Interests: Declaration of Competing Interest none., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The adsorbed vaccine SARS-CoV-2 (inactivated) produced by Sinovac (SV) was the first vaccine against COVID-19 to be used in Brazil. To understand the metabolic effects of SV in Brazilian subjects, NMR-based metabolomics was used, and the immune response was studied in Brazilian subjects. Forty adults without (group - , n = 23) and with previous COVID-19 infection (group + , n = 17) were followed-up for 90 days postcompletion of the vaccine regimen. After 90 days, our results showed that subjects had increased levels of lipoproteins, lipids, and N -acetylation of glycoproteins (NAG) as well as decreased levels of amino acids, lactate, citrate, and 3-hydroxypropionate. NAG and threonine were the highest correlated metabolites with N and S proteins, and neutralizing Ab levels. This study sheds light on the immunometabolism associated with the use of SV in Brazilian subjects from Rio de Janeiro and identifies potential metabolic markers associated with the immune status.

In this work, we present the potassium niobate (KNbO 3 ) nanoparticles as a suitable mesoporous photoelectrode for dye-sensitized solar cells (DSSCs). The KNbO 3 particles were synthesized by the microwave-assisted hydrothermal method using mild conditions and characterized by SEM, XRD, Raman, and UV-Vis diffuse reflectance. The particles presented a pyramidal tower-like shape with an orthorhombic structure and an indirect bandgap of (3.0 ± 0.1) eV. Dye-sensitized solar cells were assembled using the synthesized KNbO 3 nanoparticles, which were deposited as a photoelectrode on a TiO 2 recombination charge blocking layer. It is noticeable that the synergistic operation of the TiO 2 blocking layer and KNbO 3 photoelectrode is essential to achieve photovoltaic behaviour in our solar cells. The short-circuit current density of J sc = 2.82 mA, open-circuit voltage V oc = 669 mV, fill factor FF = 0.62, and a power conversion efficiency PCE = 1.17%, reports elevated parameters if compared to other DSSCs alternative materials, becoming potassium niobate suitable as photoelectrode.

Mucosal-associated invariant T (MAIT) cells are restricted by MR1 and are known to protect against bacterial and viral infections. Our understanding of the role of MAIT cells in parasitic infections, such as visceral leishmaniasis (VL) caused by protozoan parasites of Leishmania donovani , is limited. This study showed that in response to L. infantum , human peripheral blood MAIT cells from children with leishmaniasis produced TNF and IFN-γ in an MR1-dependent manner. The overall frequency of MAIT cells was inversely correlated with alanine aminotransferase levels, a specific marker of liver damage strongly associated with severe hepatic involvement in VL. In addition, there was a positive correlation between total protein levels and the frequency of IL-17A + CD8 + MAIT cells, whereby reduced total protein levels are a marker of liver and kidney damage. Furthermore, the frequencies of IFN-γ + and IL-10 + MAIT cells were inversely correlated with hemoglobin levels, a marker of severe anemia. In asymptomatic individuals and VL patients after treatment, MAIT cells also produced IL-17A, a cytokine signature associated with resistance to visceral leishmaniasis, suggesting that MAIT cells play important role in protecting against VL. In summary, these results broaden our understanding of MAIT-cell immunity to include protection against parasitic infections, with implications for MAIT-cell-based therapeutics and vaccines. At last, this study paves the way for the investigation of putative MAIT cell antigens that could exist in the context of Leishmania infection., Competing Interests: JM, ZC, and SE are inventor of patents describing MR1 antigens and MR1 tetramers. 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 © 2022 Moreira, Borges-Fernandes, Pascoal-Xavier, Ribeiro, Pereira, Pediongco, Araújo, Teixeira-Carvalho, de Carvalho, Mourão, Campos, Borges, Carneiro, Chen, Saunders, McConville, Tsuji, McCluskey, Martins-Filho, Eckle, Coelho-dos-Reis and Peruhype-Magalhães.)

The growth of ZnS photoelectrodes on ZnO particles identified as ZnO/ZnS(ZC + TAA) by the microwave-assisted hydrothermal method showed excellent photovoltaic parameters of J SC = 1.2 mA cm -2 and FF = 0.66, even compared to ZnS(ZC + TAA) used as a reference sample with J SC = 0.15 mA cm -2 and FF = 0.52. A careful analysis indicates that the better charge transfer and the higher resistance to recombination present in the ZnO/ZnS(ZC + TAA) samples were the origin of the best photovoltaic behavior. These assertions are supported by a set of samples synthesized from different precursors resulting in different crystal structures, which can be directly associated with current densities and fill factors. All aspects about synthesis and optical/electronic parameters associated with structural features will be available in this article.

Osmotic demyelination syndrome is an uncommon neurologic condition, characterized by noninflammatory demyelination involving the pons and other areas of the central nervous system. As chronic hyponatremia is frequently associated with cirrhosis, patients undergoing liver transplantation are at an increased risk for developing this condition. We report the case of a patient who developed refractory hypernatremia and osmotic demyelination syndrome after liver transplantation. The patient was a 40-year-old man, who underwent liver transplantation for the treatment of cryptogenic cirrhosis, and had a preoperative sodium level of 128 mmol/L. Although there were no intraoperative complications, the patient showed signs of mental confusion and drowsiness in the second postoperative day, and we noticed an increase to 136 mmol/L in his serum sodium. Treatment with 5% dextrose and desmopressin was initiated, but his serum sodium continued to increase steadily, while his neurologic condition gradually worsened. Serum sodium rose to 157 mmol/L, and a magnetic resonance imaging of the brain showed extensive lesions consistent with osmotic demyelination syndrome. The clinical condition of the patient continued to deteriorate until his death 17 days after the transplant. Although the occurrence of this syndrome after liver transplantation is well described, the steady increase in serum sodium despite early treatment, as described in this case, is highly unusual, and highlights the great attention that must be taken with monitoring and control of serum sodium in patients who undergo liver transplant in the context of chronic hyponatremia. This manuscript is compliant with the Helsinki Congress and the Istanbul Declaration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HL) is a rare syndrome characterized by a hyperinflammatory state, resulting from an excessive but ineffective immune response. There is a continuous stimulation of TCD8 + lymphocytes, associated with an uncontrolled release of cytokines, causing the infiltration of multiple organs by histiocytes and activated lymphocytes. HL can be a primary condition as a consequence of genetic disorder that most often affects children, or it can be secondary to neoplasms, autoimmune conditions or various infectious diseases in patients of all ages. HL caused by infection by Mycobacterium tuberculosis is highly unusual, with few cases reported in the literature. There is no clinical manifestation or laboratorial finding that is specific to HL, and a high index of clinical suspicion is necessary for the correct diagnosis, which is usually confirmed by biopsy. Treatment consists of controlling the causative event and the use of immunosuppressant drugs such as corticosteroids, etoposide, and cyclosporine to suppress the exacerbated immune response. We report the case of a patient who developed HL 2 months after liver transplantation. The initial presentation was persistent fever, prompting a search for a site of infection and the use of broad-spectrum antibiotics. As the clinical condition of the patient continued to deteriorate, HL was diagnosed through a bone marrow biopsy, and a cerebrospinal fluid culture positive for M. tuberculosis established the diagnosis of disseminated tuberculosis. Despite optimal treatment with immunosuppressors and antituberculosis drugs, there was no significant response and the patient died. This article is compliant with the Helsinki Congress and the Istanbul Declaration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Zinc titanates are compounds that have shown great application versatility, including in the field of semiconductors. Solid state reactions, the polymeric precursor method and the hydrothermal method are the most mentioned synthesis of these compounds in the literature. In the present work, we use microwave assisted hydrothermal method (MAH) to synthesize zinc titanate and evaluate its potential for solar cell applications through structural and optical characterization techniques. The synthesized samples were also subjected to a variable temperature heat treatment in the range of 500 °C-800 °C. The analysis showed that the crystallization of the material starts at 500 °C and that samples submitted to temperatures of 600 °C-800 °C showed the formation of two phases of zinc titanates, being a cubic phase of ZnTiO 3 , considered rare in the literature, predominant up to a temperature of 800 °C. The optical characterization, based on the techniques of photoluminescence spectroscopy and UV-Visible spectroscopy, showed that the photoluminescent activity and the energy of the band gap increased with the increase of the temperature of the heat treatment, having the highest response in 700 °C, facts that can be linked to the predominant formation of the cubic phase of ZnTiO 3 and simultaneous of the cubic and rhombohedral phases of ZnTiO 3 at 700 and 800 °C. Finally, we highlight as the most important results, the fact that it was possible to obtain these titanates at a temperature lower than that reported in the literature, and that the heat-treated sample at 500 °C is the one with the lowest energy expenditure to be synthesized and the one with the greatest potential for application in dye-sensitized solar cells (DSSC's)., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

The dynamics of CD4 + T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4 + T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T H 1) and follicular helper T (T FH ) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T H 1 and T FH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T FH and central memory were revealed, with antimalarials modulating these responses and boosting T H 1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4 + T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).

Inorganic hybrid materials have promising applications in absorbers and for the photon harvesting of solar irradiation, such as in DSSC photoanodes. Moreover, investigation of the interactions between the photoanode constituent materials is extremely important, since it is known that the properties of the materials are strongly dependent on the nucleation and growth process. Therefore, the purpose of this work was to synthesize a system consisting of a synergic combination of two inorganic hosts, BaTiO 3 and CaF 2 , synthesized together through a microwave-assisted hydrothermal method, which allows single-phase materials to be obtained after short synthesis times and at low temperatures. The increase in optical activity was investigated after the insertion of Eu ions. From the structural results, it was possible to observe that the method used to obtain the system was efficient, even using temperatures as low as 140 °C and a reaction time of one minute. The optical properties (emission and excitation) were evaluated in the visible and VUV region from 2.5 to 10.5 eV. The XANES Eu L iii edge differences associated with the XEOL results indicate that the synthesis method incorporated Eu 3+ in the hosts and the surface of the two compounds, BaTiO 3 and CaF 2 . Therefore, the combination between the Eu 3+ activators and the F centers of the host increased the range for photon harvesting, making these systems a promising material for future applications in photoanodes for DSSCs.

Here, we have studied the crystalline structure of bulk ZnX (X = O, S, Se, Te) and ZnF 2 systems as a first step to understand the structures like ZnX and Zn-based systems like ZnO/ZnF 2 interfaces, which are of utmost importance for possible technological applications. In addition, an adequate methodological description based on density functional theory (DFT) calculations is necessary. It is well known that plain DFT calculations based on local or semilocal exchange-correlation functionals fail to describe the correct band gap energy for these systems, whereas nonlocal approaches, such as hybrid-based functionals, can compensate the underestimation of band gap. To contribute to the assessment, DFT studies were performed within semilocal Perdew-Burke-Ernzerhof (PBE) and two nonlocal functionals, hybrid Heyd-Scuseria-Ernzerhof (HSE) and PBE + U functionals. Our results confirm that PBE underestimates the energy band gap values, from 33.0 to 42.8% for ZnX compounds compared to the experimental values. Applying the hybrid HSE functional, we obtained a band gap dependency in relation to the range of separation of the nonlocal exact exchange, in general decreasing the band gap error and improving the lattice constant description. In addition, using the PBE + U approach, we have investigated the localization of the Zn d-states and its effect on the band gap in ZnX and ZnF 2 . We found an increase in the band gap with increasing Hubbard parameter, which introduces on-site Coulomb corrections for the Zn 3d states. In the same context, the relevance to include the Hubbard corrections for the O 2p states (and X p states) is highlighted. Thus, considering PBE + U , the error in ZnO band gap, for example, decreases to 5.1%, in relation to the experimental value. Finally, ZnO-12L/ZnF 2 -4L superlattices are found to exhibit conventional electronic properties, such as low fundamental band gap, smaller than either of the parent materials. Our first-principles calculations reveal that the unexpected band gap reduction is induced by the conducting layers that tend to penetrate the interface and decrease the band gap, leading to the transport of carriers through the interface to ZnF 2 , which, even with a high band gap for charge transfer, can be interesting for photovoltaic applications.

Mucosal-associated invariant T (MAIT) cells are important for immune responses against microbial infections. Although known to undergo marked numerical changes with age in humans, our understanding of how MAIT cells are altered during different phases across the human life span is largely unknown. Although also abundant in the tissues, our study focuses on MAIT cell analyses in blood. Across the human life span, we show that naive-like MAIT cells in umbilical cord blood switch to a central/effector memory-like profile that is sustained into older age. Whereas low-grade levels of plasma cytokine/chemokine were apparent in older donors (>65 y old), surprisingly, they did not correlate with the ex vivo MAIT hyperinflammatory cytokine profile observed in older adults. Removal of MAIT cells from older individuals and an aged environment resulted in the reversal of the baseline effector molecule profile comparable with MAIT cells from younger adults. An upregulated basal inflammatory profile accounted for reduced Escherichia coli -specific responses in aged MAIT cells compared with their young adult counterparts when fold change in expression levels of GzmB, CD107a, IFN-γ, and TNF was examined. However, the magnitude of antimicrobial MR1-dependent activation remained as potent and polyfunctional as with younger adults. Paired TCRαβ analyses of MAIT cells revealed large clonal expansions in older adults and tissues that rivalled, remarkably, the TCRαβ repertoire diversity of virus-specific CD8 + T cells. These data suggest that MAIT cells in older individuals, although associated with large clonal TCRαβ expansions and increased baseline inflammatory potential, demonstrate plasticity and provide potent antimicrobial immunity., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Material processing has become essential for the proper control, tuning and consequent application of the properties of micro/nanoparticles. In this case, we report herein the capability of the microwave-assisted hydrothermal (MAH) method to prepare the SrTiO3 compound, as a case study of inorganic compounds. Analyses conducted by X-ray diffraction, X-ray photoelectron and X-ray absorption spectroscopies confirmed that the MAH route enables the formation of pristine SrTiO3. The results indicated that the combination of thermal and non-thermal effects during the MAH treatment provides ideal conditions for an efficient and rapid synthesis of pristine SrTiO3 mesocrystals. Scanning electron microscopy images revealed a cube-like morphology (of ca. 1 μm) formed via a self-assembly process, influenced by the MAH time. Additionally, photoluminescence measurements revealed a broad blue emission related to intrinsic defects, which decreased with the MAH synthesis time.

Cu 2 O low-index surfaces periodic models have been simulated based on density functional theory. The calculated surfaces energies allowed estimating the morphology by means of the Wulff theorem as well as the investigation of possible paths of morphological changes. Therefore, systematic morphology diagrams and change paths according to the energy modulation in relation to the surfaces stabilizations were elaborated. The applicability of this strategy was exemplified by comparing the obtained results with experimental available data from the literature. The morphology diagrams with the quantitative energetic point of view can be used as a guide to support experimental works in order to understand the relation between surface interactions and crystal growth., (© 2019 The Authors.)

Objectives: To characterize the plasmatic profile of cell-derived microvesicles (MVs) at diagnosis and during the treatment of patients with infective endocarditis (IE)., Methods: Blood samples from 57 patients with IE were obtained on 3 consecutive moments: upon admission (T0), at 2 weeks (T1), and at the end of treatment (T2), and were compared with 22 patients with other bacterial infections. MPs were measured by flow cytometry and labeled for specific cell markers of CD45 (leukocytes), CD66b (neutrophils), CD14 (monocytes), CD41a (platelets), CD51 (endothelial cells), CD3 (T lymphocyte) and CD235a (erythrocytes)., Results: MVs from platelets (pltMVs), leukocytes (leukMVs), neutrophils (neutMVs), monocytes (monoMVs) and lymphocytes (lymphMVs) were significantly more elevated in the patients with IE, compared to the patients with other bacterial infections, despite comparable age, sex, blood counts and C-reactive protein levels. MVs values revealed a relatively stable pattern over time in IE, except for a significant increase in leukMVs and neutMVs in T1. LeukMVs (p = 0.011), neutMVs (p = 0.010), monoMVs (p = 0.016) and lymphMVs (p = 0.020), measured at admission, were significantly higher in IE patients that died during hospitalization in comparison with those that survived. In a multivariable analyses, the levels of neutMVs remained as an independent factor associated with mortality (odds ratio 2.203; 95% confidence interval 1.217 - 3.988; p = 0.009), adjustment for heart failure during the treatment., Conclusions: Plasma levels of pltMVs, leukMVs, neutMVs, monoMVs and lymphMVs were significantly more elevated in patients with IE than in patients with other bacterial infections at hospital admission. Furthermore, neutMVs at admission have been identified as an independent predictor of mortality in patients with IE. Thus, cell derived MPs may become an important tool in the differential diagnosis and mortality risk assessment early in the course of IE suspected cases., (Copyright © 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to identify phenotypic and functional biomarkers associated with distinct clinical status of leprosy or leprosy reactions. The study included tuberculoid/borderline (BB/BT/T) and lepromatous (BL/L) leprosy poles as well as Type-1 and Type-2 leprosy reactions along with healthy controls (NI). A range of peripheral blood biomarkers of innate (neutrophils - NEU and monocytes - MON) and adaptive immunity (CD4 + and CD8 + T-cells) were evaluated ex vivo and upon in vitro stimuli with M. leprae antigen. Data analysis allowed the selection of NEUTLR4 + (ex vivo) and CD4 + IL-10 + (in vitro) as universal biomarkers increased in all leprosy patients and those exhibiting leprosy reactions. A range of biomarkers were commonly found in both poles of leprosy patients, including decreased levels of MONTGF-β + (ex vivo) and increased levels of MONTNF-α + , CD4 + TGF-β + , CD8 + TLR2 + , CD8 + TNF-α + , CD8 + IL-4 + and CD8 + TGF-β + (in vitro). Noteworthy was that MONHLA-DR + (ex vivo) and CD8 + IL-10 + (in vitro) were particularly found in BL/L patients. Leprosy patients with Type-1 reaction exhibited a larger list of altered biomarkers, mainly involving activation markers (TLR2, TLR4, HLA-DR and DAF-2T) in NEU and MON along with CD4 + and CD8 + cells. In summary, this study provided insights about immunological features of leprosy poles and leprosy reactional episodes with putative applicability, including novel biomarkers for complementary diagnosis and future therapeutic approaches in clinical studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Piperlongumine is an amide alkaloid found in Piperaceae species that shows a broad spectrum of biological properties, including antitumor and antiparasitic activities. Herein, the leishmanicidal effect of piperlongumine and its derivatives produced by a biomimetic model using metalloporphyrins was investigated. The results showed that IC 50 values of piperlongumine in promastigote forms of Leishmania infantum and Leishmania amazonensis were 7.9 and 3.3 µM, respectively. The IC 50 value of piperlongumine in the intracellular amastigote form of L. amazonensis was 0.4 µM, with a selectivity index of 25. The piperlongumine biomimetic derivatives, Ma and Mb, also showed leishmanicidal effects. We also carried out an in vitro metabolic degradation study showing that Ma is the most stable piperlongumine derivative in rat liver microsome incubations. The results presented here indicate that piperlongumine is a potential leishmanicidal candidate and support the biomimetic approach for development of new antileishmanial derivatives., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

The engineering of semiconductor materials for the development of solar cells is of great importance today. Two topics are considered to be of critical importance for the efficiency of Grätzel-type solar cells, the efficiency of charge separation and the efficiency of charge carrier transfer. Thus, one research focus is the combination of semiconductor materials with the aim of reducing charge recombination, which occurs by spatial charge separation. From an experimental point of view, the combining of materials can be achieved by decorating a core with a shell of another material resulting in a core-shell system, which allows control of the desired photoelectronic properties. In this context, a computational simulation is mandatory for the atomistic understanding of possible semiconductor combinations and for the prediction of their properties. Considering the construction of ZnO/ZnX (X = S, Se or Te) interfaces, we seek to investigate the electronic influence of the shell (ZnX) on the core (ZnO) and, consequently, find out which of the interfaces would present the appropriate properties for (Grätzel-type) solar cell applications. To perform this study, we have employed density functional theory (DFT) calculations, considering the Perdew-Burke-Ernzerhof (PBE) functional. However, it is well-known that plain DFT fails to describe strong electronic correlated materials where, in general, an underestimation of the band gap is obtained. Thus, to obtain the correct description of the electronic properties, a Hubbard correction was employed, i.e. PBE+U calculations. The PBE+U methodology provided the correct electronic structure properties for bulk ZnO in good agreement with experimental values (99.4%). The ZnO/ZnX interfaces were built and were composed of six ZnO layers and two ZnX layers, which represents the decoration process. The core-shell band gap was 2.2 eV for ZnO/ZnS, ∼1.71 eV for ZnO/ZnSe and ∼0.95 eV for ZnO/ZnTe, which also exhibited a type-II band alignment. Bader charge analysis showed an accumulation of charges in the 6th layer of ZnO for the three ZnO/ZnX interfaces. On the basis of these results, we have proposed that ZnO/ZnS and ZnO/ZnSe core-shell structures can be applied as good candidates (with better efficiency) for photovoltaic devices.

Vitamin D supplementation is universal for postmenopausal women, but not for elderly men, in whom osteoporosis is also commonly neglected. This study aimed to evaluate vitamin D deficiency and its association with secondary hyperparathyroidism, bone resorption, and bone density in Brazilian men. A total of 120 men, 20-93 years, were evaluated for serum calcium, phosphorus, creatinine, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, biochemical markers of bone resorption (carboxy-terminal telopeptide, carboxy-terminal peptide of type I collagen), and bone mineral density (dual-energy X-ray absorptiometry). Glomerular filtration rate (GFR) below 30 mL/min/1.73 m 2 , chronic diseases, and medications affecting bone were the exclusion criteria. No participant reported previous low-impact fractures. In the overall population, 25(OH)D levels were below 30 ng/mL in 46.7%, and below 20 ng/mL in 27.6%. Among the 93 patients 50 years and older, 28 had osteoporosis. In those 70 years and older, the prevalence of vitamin D deficiency (42.1%), secondary hyperparathyroidism (46.4%), high bone resorption (39.6%), decreased GFR (39.2%), and osteoporosis (41.4%) was significantly higher than in the younger subjects (p < 0.005 for all comparisons). Serum parathyroid hormone increased with aging and declining GFR, but was not significantly associated with 25(OH)D or bone mineral density. There was a clear contribution of vitamin D deficiency to increased bone resorption and osteoporosis. Binary logistic regression model considering age, 25(OH)D, and bone resorption identified age ≥70 years as the main determinant of osteoporosis. Our data demonstrate a high prevalence of vitamin D deficiency in a male population living in Rio de Janeiro, and emphasize its participation on the pathogenesis of age-related bone loss. (Vitamin D deficiency and osteoporosis are common in elderly Brazilian men.)., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Statement of Problem: The color of dental poly(methyl methacrylate) (PMMA) is conventionally rendered by organic and inorganic pigments, which are usually not bonded to the polymer network. Functionalized ceramic pigments can be used to color PMMA, allowing improved chemical interaction with the resin matrix., Purpose: The purpose of this in vitro study was to synthesize, functionalize, and characterize pink manganese-doped alumina ceramic pigments. The hypothesis tested was that functionalized ceramic pigments would render pink coloration to a translucent PMMA without jeopardizing its mechanical properties., Material and Methods: Pink alumina powders doped with 1 or 2 mol% of manganese (Al 2 O 3 :Mn) were prepared by means of a polymeric precursor method. Pigment (Pig.) particles were functionalized with a silica coating method followed by silanation before preparation of PMMA-based composite resins (5 wt% pigment). The color of composite resins (Pig.1% and Pig.2%) and PMMA controls (Pink and translucent [Trans]) was evaluated (CIELab color coordinates), and their mechanical properties were tested (3-point bending)., Results: The microstructure of the pigment particles showed approximately 55-nm nanocrystals of manganese-doped α-alumina clustered into irregular porous particles up to 60 μm. The composite resins and pink PMMA showed similar color parameters (CIE a* pink=20.1, Pig.1%=14.6, Pig.2%=16.0, Trans=0.19, P<.001; CIE b* Pink=17.0, Pig.1%=18.6, Pig.2%=19.0, Trans=2.52, P<.001). No statistical differences were observed in mechanical properties among groups (σ f pink=98.4, Pig.1%=98.1, Pig.2%=98.8, trans=89.1, P=.136)., Conclusions: The addition of the functionalized pink ceramic pigments to a translucent PMMA yielded similar coloration to that of the regular pink PMMA used in dentistry and did not jeopardize its mechanical properties., (Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes., Methods: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations., Results: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397)., Conclusions: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway. Indirect activation is also observed during chronic viral infections by and IL-12/IL-18 pathway. In this review, the mechanisms of activation, the timeline of MAIT-cell development in humans as well as their role in human infection are discussed. On the whole, we believe that harnessing the anti-microbial ability of MAIT-cells could contribute for the design of potent immunotherapies and vaccines against "hard-to-kill" infectious agents that remain as public health threats worldwide., (Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Visceral leishmaniasis (VL) is transmitted by phlebotomine sandfly vectors and domestic dogs serve as a reservoir. The elimination of seropositive dogs has been a recommended strategy for managing the disease in Brazil. A protective canine vaccine would be an important tool for controlling the disease, reducing the parasites available to sandfly vectors and, consequently, reducing the number of human VL cases. Leishmune(®) is an anti-canine Leishmaniosis (VL Canine) vaccine produced by Zoetis (Pfizer, Brazil) that was commercially available in Brazil until 2014. The main goal of the present study was to investigate the protective immunological events induced by vaccination with Leishmune(®) in the time frame of one year. Healthy, non-vaccinated dogs and dogs of 1, 6 and 10 months post-vaccination were evaluated. Results showed that Leishmune(®) induced an increase in phagocytic activity of neutrophils and monocytes and also increased NO production. Immunological events were correlated with functional responses, as high levels of IgG and an increase of the receptor Fcγ were detected. Vaccination induced an increased expression of TLR (2, 4, 5, 9), integrin (CD29, CD49f), activation (MHCII) and co-stimulatory (CD80, CD81) molecules by neutrophils and monocytes. Vaccination led to decrease of IL-4 and an increase of IL-8 production by monocytes and higher IFN-γ and IL-17 production by T-cells. The results suggested that Leishmune(®) was able to induce a long-lasting change in immune response, mediated by supportive immunological events that may be participating in protective immunity against CL., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Even though heart diseases are amongst the main causes of mortality and morbidity in the world, existing treatments are limited in restoring cardiac lesions. Cell transplantations, originally developed for the treatment of hematologic ailments, are presently being explored in preclinical and clinical trials for cardiac diseases. Nonetheless, little is known about the possible efficacy and mechanisms for these therapies and they are the center of continuous investigation. In this scenario, noninvasive imaging techniques lead to greater comprehension of cell therapies. Radiopharmaceutical cell labeling, firstly developed to track leukocytes, has been used successfully to evaluate the migration of cell therapies for myocardial diseases. A substantial rise in the amount of reports employing this methodology has taken place in the previous years. We will review the diverse radiopharmaceuticals, imaging modalities, and results of experimental and clinical studies published until now. Also, we report on current limitations and potential advances of radiopharmaceutical labeling for cell therapies in cardiac diseases.

Background: The process for obtaining monoclonal antibodies against a specific antigen is very laborious, involves sophisticated technologies and it is not available in most research laboratories. Considering that most cytokines remain partially conserved among species during evolution, the search for antibody cross-reactivity is an important strategy for immunological studies in veterinary medicine. In this context, the amino acid sequence from human and canine cytokines have demonstrated 49-96 % homology, suggesting high probability of cross-reactivity amongst monoclonal antibodies. For this, 17 commercially available anti-human monoclonal antibodies [IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8 (#1, #2), IL-10, IL-12, IL-13, IL-17A, IFN-γ (#1, #2), TNF-α (#1, #2) and TGF-β], were evaluated in vitro for intracellular cytokine detection in a stimulated canine blood culture by flow cytometry and confocal microscopy. Lymphocytes from peripheral blood of healthy and two unhealthy dogs were analyzed., Results: Eleven anti-human mAbs [IL-1α, IL-4, IL-5, IL-6, IL-8 (#1, #2), IL-12, IL-17A, TNF-α (#1, #2) and TGF-β] cross-reacted against canine intracellular cytokines. The specificity of the assays was not affected after Fc-blocking. Three anti-human cytokine mAbs [IL-4, IL-8 (#2) and TGF-β] when evaluated by confocal microscopy also cross-reacted with intracellular canine cytokines. The identification of human mAbs that cross-reacted with canine cytokines may support their use as immunological biomarkers in veterinary medicine studies., Conclusion: The identification of these 11 anti-human cytokine mAbs that cross-reacted with canine cytokines will be useful immunological biomarkers for pathological conditions by flow cytometry and fluorescence microscopy in dogs.

A microwave-assisted hydrothermal method was applied to synthesize BaZr1-xHfxO3, (BZHO) solid solutions at a low temperature, 140 °C, and relatively short times, 160 min. The detailed features of the crystal structure, at both short and long ranges, as well as the crystal chemistry doping process, are extensively analysed. X-ray diffraction measurements and Raman spectroscopy have been used to confirm that pure and Hf-doped BZO materials present a cubic structure. Extended X-ray absorption fine structure (EXAFS) spectra indicate that Hf(4+) ions have replaced the Zr(4+) ions on the 6-fold coordination and a subsequent change on the Ba(2+) 12-fold coordination can be sensed. X-ray absorption near-edge structure (XANES) spectroscopy measurements reveal a local symmetry breaking process, associated to overlap of the 4d-2p and 5d-2p orbitals of Zr-O and Hf-O bonds, respectively. Field emission scanning electron microscopy (FE-SEM) and high resolution transmission electron microscopy (HRTEM) show the mesocrystalline nature of self-assembled BZHO nanoparticles under a dodecahedron shape. In addition first principle calculations were performed to complement the experimental data. The analysis of the band structures and density of states of the undoped BZO and doped BZHO host lattice allow deep insight into the main electronic features. The theoretical results help us to find a correlation between simulated and experimental Raman modes and allow a more substantial interpretation of crystal structure.

Background: The main control strategy for visceral leishmaniasis in Brazil has been based on the elimination of seropositive dogs, although this is not widely accepted. In this context, the use of a long-lasting protective vaccine against canine visceral leishmaniasis (CVL) has been highly expected. The aim of this work was to determine the timeline kinetics of the cytokine microenvironment derived from circulating leukocytes as supportive immunological biomarkers triggered by Leishmune® vaccine. Cross-sectional kinetic analysis of cellular immunity cytokines was carried out at three times (1, 6 and 12 months) after primovaccination with Leishmune®. In vitro short-term whole blood cultures were stimulated with Leishmania infantum soluble antigen (SLAg). The secreted cytokine signatures and their major sources were determined., Results: At six months after vaccination, Leishmune® induced an increase in IL-8, IFN-γ, IL-17a and TNF-α levels and a decrease in IL-10. Cytokine signature analysis revealed a shift in the microenvironment towards a pro-inflammatory profile mediated by IL-8 and IFN-γ. Both, CD4(+) (↑TNF-α(+) and ↑IFN-γ (+)) and CD8(+) (↑IL-17a and ↓IL-4) T-cells contributed to the acquired immune responses observed after stimulation with SLAg., Conclusions: The changes observed in the cytokine profile suggested that Leishmune® was able to induce an effective response at six months after primovaccination. After one year, it returned to baseline suggesting the need of additional boosting.

OBJECTIVE To describe the migration flows of demand for public and private hospital care among the health regions of the state of Sao Paulo, Brazil.METHODS Study based on a database of hospitalizations in the public and private systems of the state of Sao Paulo, Southeastern Brazil, in 2006. We analyzed data from 17 health regions of the state, considering people hospitalized in their own health region and those who migrated outwards (emigration) or came from other regions (immigration). The index of migration effectiveness of patients from both systems was estimated. The coverage (hospitalization coefficient) was analyzed in relation to the number of inpatient beds per population and the indexes of migration effectiveness.RESULTS The index of migration effectiveness applied to the hospital care demand flow allowed characterizing health regions with flow balance, with high emigration of public and private patients, and with high attraction of public and private patients.CONCLUSIONS There are differences in hospital care access and opportunities among health regions in the state of Sao Paulo, Brazil.

We report two similarly affected cousins (children of monozygotic twin sisters) with phenotypic features consistent with 9p deletion syndrome, including dysmorphic craniofacial features (trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures and long philtrum), intellectual disability and disorders of sex development. Initial cytogenetic examination showed normal karyotypes in the probands and their respective parents, though multiplex ligation probe amplification revealed a 1q terminal duplication and a 9p terminal deletion in both affected children. Further analysis by fluorescence in situ hybridization, identified a familial balanced cryptic translocation t(1;9)(q44;p23) in the mothers, showing the importance of the association of molecular cytogenetic techniques in clinical genetics, given the implications for the care of patients and for genetic counseling.

We report herein a detailed study on the influence of microwave-assisted hydrothermal (MAH) treatment time on both long and short range structures around Ti atoms of SrTiO3 powders. Few studies have been carried out on short-order structural properties as well as the relationship between the local order and the SrTiO3 photocatalytic properties. We use X-ray diffraction to determine the long-range structure, while the local environment around the Ti atom is probed with X-ray absorption spectroscopy and the vibration frequencies are investigated by Raman spectroscopy. The faster crystallization of SrTiO3 powders provided by the MAH system resulted in large distortions of Ti-O bond lengths which remain unchanged even for a longer MAH treatment time. Despite the long-range structure being associated with ideal TiO6 clusters, X-ray absorption spectroscopy measurements identified the presence of undercoordinated TiO5 clusters. Compared with the reference bulk SrTiO3, the hierarchical SrTiO3 cube-like shape showed enhanced photocatalytic activity, which was associated with the presence of these TiO5 clusters. Field emission scanning electron microscopy (FE-SEM) revealed that the superstructures based on a cube-like shape are formed by an assembly process, becoming well defined as a function of MAH treatment time.

The objective of this study was to analyze admissions in the hospital health care system in Brazil in the year of 2006, starting from the admitted subjects. The initial data were the admissions SUS (SIH), non-SUS (CIH) in 2006 and 2007. The identification of the individual was by probabilistic method of associations of registrations (linkage) and, for the composition of the admission data, specific algorithms were applied to the data. A total of 12,391,990 admissions with at least one day in hospital in the year of 2006 were analyzed. The imprecise nature of the probabilistic method at a certain degree, the adoption of conservative parameters in order to avoid the inclusion of false positive, and the subnotification of CIH represent possible limitations of this study. The Hospital Services System in Brazil presented admission rate of 5.6% in total, 5.0% SUS and 1.6% non-SUS, with differences according to age and region. The non-SUS admissions data collected by CIH give important additional information to the analysis of the hospital utilization in the country. The SUS administrative data are valid for analyses of admissions and the algorithms for admission data composition enhance the analysis of the Hospital Services System in Brazil.

Background: Safety transport boxes are increasingly used to ship laboratory specimens but there is little information on their capacity to maintain suitable transportation temperatures., Materials and Methods: Inner temperature was assessed using a commercially available transport box during an 8-h transportation period in the heat., Results: Temperature stability was unsatisfactory during approximately 64% of the transportation time (i.e., from 125 to 450 min)., Conclusions: Transport boxes might be unsuitable for shipping specimens over long periods., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Periodic first-principles calculations based on density functional theory at the B3LYP level has been carried out to investigate the photoluminescence (PL) emission of BaZrO(3) assembled nanoparticles at room temperature. The defect created in the nanocrystals and their resultant electronic features lead to a diversification of electronic recombination within the BaZrO(3) band gap. Its optical phenomena are discussed in the light of photoluminescence emission at the green-yellow region around 570 nm. The theoretical model for displaced atoms and/or angular changes leads to the breaking of the local symmetry, which is based on the refined structure provided by Rietveld methodology. For each situation a band structure, charge mapping, and density of states were built and analyzed. X-ray diffraction (XRD) patterns, UV-vis measurements, and field emission scanning electron microscopy (FE-SEM) images are essential for a full evaluation of the crystal structure and morphology.

Purpose: karyotype is a well established technique in the study of spontaneous miscarriages but is associated with selective overgrowth of maternal cells and other culture artefact (spp) such as tetraploidy, which could mask the true karyotype of the conceptus., Methods: 328 cases of pregnancy losses were studied by karyotype and Multiplex Ligation Dependent Probe Amplification technique. Touch FISH performed in non-cultured cells was used to evaluate the ploidy complement and sex discrepancies using centromeric probes for chromosomes X, Y and 18., Results: touch FISH confirmed 13 cases of maternal contamination, identified a triploidy and a monosomy X. True tetraploidy was confirmed in 7/14 cases studied., Conclusion: touch FISH protocol is extremely accurate in the distinction of genuine mosaicism from tissue culture artifacts namely in cases with suspicion of tetraploidy and can be used to confirm maternal cell contamination in cases with sex discrepancy between karyotype and MLPA.

Introduction: Lowe Syndrome, or Oculocerebrorenal Dystrophy (OCRL), has a recessive inheritance linked to X chromosome. It presents cataracts and glaucoma, delay in neuropsychomotor development, cognitive deficits, and renal Fanconi syndrome., Objective: Describe five patients with OCRL, attended at Tubulopathy outpatient clinic., Method: We performed a retrospective assessment of 5 male patient clinical charts of OCRL patients., Results: Mean age at first consultation was 76.5 and mean follow up interval was 30.5 months (8-53 months). Symptoms and clinical signs included cataracts and nystagmus. Neuropsychomotor development and weight and height deficits were present in whole cases, as well as polyuria, polydipsia, and intestinal constipation, metabolic acidosis, phosphaturia, bicarbonaturia, proteinuria, hypercalciuria, hyperuricosuria. Nephrocalcinosis was identified in one, renal lithiasis in three, and reduced kidney size in two patients. We found pathological fractures and rachitism in two, bone rarefaction and delay of bone age in all of the patients. One patient presented a reduction in the rhythm of glomerular filtration. Therapeutically, all patients received alkali, phosphorus and vitamin D reposition in addition to a dietary orientation adequate to their needs., Conclusion: This study emphasizes the importance of early diagnosis and medico-nutritional followup, to avoid complications related to metabolic disturbances.

The emission of wide band photoluminescence showed a synergic effect on barium zirconate and barium titanate thin films in alternate multilayer system at room temperature by 488 nm exiting wavelength. The thin films obtained by spin-coating were annealed at 350, 450, and 550 degrees C for 2 h. The X-ray patterns revealed the complete separation among the BaTiO3 and BaZrO3 phases in the adjacent films. Visible and intense photoluminescence was governed by BaZrO3 thin films in the multilayer system. Quantum mechanics calculations were used in order to simulate ordered and disordered thin films structures. The disordered models, which were built by using the displacement of formers and modifier networks, showed a different symmetry in each system, which is in accordance with experimental photoluminescence emission, thus allowing to establish a correlation among the structural and optical properties of these multilayered systems.

The aim of this study was to verify the occurrence of intestinal parasites and commensal organisms among children attending a school located in a settlement of 'landless farm workers' in Campo Florido, Minas Gerais, Brazil. Coproparasitological analyses performed on 72 school children revealed 59.7% positivity and 4 types of protozoa and 5 types of helminths were identified. It can be concluded that it is necessary to monitor the health conditions of this population.

OBJECTIVE: To analyze the clinical history and evolution of children and adolescents with IH, emphasizing some of their peculiar features. METHODS: We followed 471 patients with IH at an outpatient clinic. Patients were submitted to the following protocol: abdominal X-ray, kidney and urinary tract ultrasonography; urinary ionogram, blood gas and biochemical analyses; 24-hour urine for measurement of calcium and other electrolytes and creatinine; urinalysis, urine culture and phase-contrast microscopy; second morning urine collected after fasting for measurement of calcium and creatinine. RESULTS: At the time of diagnosis, 6% of the patients were infants, 15% pre-school children, 55% school children, and 24% adolescents; 56% of them were boys. Clinical and laboratory findings were: 47% had hematuria and abdominal pain, 31% had isolated hematuria, 14% isolated abdominal pain, and 8% had urinary tract infection, nocturnal enuresis, suprapubic pain or urethralgia, or the frequency/urgency syndrome with urinary incontinence. Hypercalciuria was associated with urolithiasis in 56% of patients. There was association with hyperuricosuria in 18.5% of the cases, and hypocitraturia in 8.5% of the cases. Evolution was poor for 33% of the patients, with recurrence of nephrolithiasis, persistence of hematuria, and abdominal pain. CONCLUSIONS: IH must be diagnosed and treated with criteria in order to reduce consequences such as hematuria, abdominal pain, urinary stone formation and possible bone involvement. Signs and symptoms such as urgency and urinary incontinence, suprapubic pain and nocturnal enuresis may result from renal hyperexcretion of calcium.