Intranasal Administration of Sugarcane Ash Causes Chronic Kidney Disease in Rats.

Background. Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease of unknown etiology (CKDu). However, while the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here we investigate whether sugarcane ash can induce CKD in rats. Methods. Sugarcane ash was administered for 13 weeks into the nares of rats (5 mg/day for 5d/week), and blood, urine and kidney tissues were collected at 13 weeks (at the end of ash administration) and in a separate group of rats at 24 weeks (11 weeks after stopping ash administration). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) measured. Results. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver and spleen of rats. Mild proteinuria developed although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis, and tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker, LAMP-1, showed decreased staining in ash administered rats consistent with lysosomal activation. Conclusion. Sugarcane ash containing silica nanoparticles can cause CKD in rats.

Monocytes and Macrophages in Kidney Disease and Homeostasis.

The monocyte-macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages' roles in different renal compartments and common renal diseases.

Climate change and nephrology.

Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.

2 × 4 appliance in the mixed dentition stage: a scoping review of the evidence.

A great emphasis is currently given to the early correction of malocclusions to prevent further complications if left untreated. Interceptive orthodontics not only simplifies but also eliminates the need for later procedures. The 2 × 4 appliance is an orthodontic treatment modality applied during the mixed dentition period, particularly for malpositioned permanent upper incisors. This scoping review was aimed to examine the breadth and depth of the published literature on this clinical topic, as well as knowledge gaps, about this fixed appliance during mixed dentition, for the correction of incipient anterior malocclusions (incisor crowdings, midline diastemas, or crossbites). PubMed, Cochrane Library, Google Scholar, Dentistry & Oral Sciences Source, and two grey literature databases were explored; under a structured PICO question (Patient, Intervention, Comparison, Outcome) and eligibility criteria, for relevant clinical trials, observational studies, and case reports/series (in English or Spanish), using different searching terms. Titles and abstracts were screened. Full-text articles were critically reviewed for bias risk and a data charting table was constructed. 161 references were identified, after which 115 titles remained after removing duplicates. After the abstract screening, 18 potential full-text articles were reviewed. Finally, 16 studies were included, according to the performed critical appraisal. The 2 × 4 appliance is suitable for mixed dentition patients with mild or severe malocclusions, particularly when removable appliance usage is a critical problem.

Inhaled silica nanoparticles cause chronic kidney disease in rats.

Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at week 13) that continued to inflammation and chronic fibrosis at week 26 despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at week 13, and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At week 26, there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology.NEW & NOTEWORTHY Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.

Viability of ex-vivo myography as a diagnostic tool for rectus abdominis muscle electrical activity collected at Cesarean section within a diamater cohort study.

BACKGROUND: Ex-vivo myography enables the assessment of muscle electrical activity response. This study explored the viability of determining the physiological responses in muscles without tendon, as rectus abdominis muscle (RAM), through ex-vivo myography to assess its potential as a diagnostic tool. RESULTS: All tested RAM samples (five different samples) show patterns of electrical activity. A positive response was observed in 100% of the programmed stimulation. RAM 3 showed greater weight (0.47 g), length (1.66 cm), and width (0.77 cm) compared to RAM 1, RAM 2, RAM 4 and RAM 5 with more sustained electrical activity over time, a higher percentage of fatigue was analyzed at half the time of the electrical activity. The order of electrical activity (Mn) was RAM 3 > RAM 5 > RAM 1 > RAM 4 > RAM 2. No electrical activity was recorded in the Sham group. CONCLUSIONS: This study shows that it is feasible to assess the physiological responses of striated muscle without tendon as RAM, obtained at C-section, under ex vivo myography. These results could be recorded, properly analyzed, and demonstrated its potential as a diagnostic tool for rectus abdominis muscle electrical activity.

Chiral NMR analysis reveals the environmental dependence of areolal scalemization in Piptothrix areolare.

The occurrence of racemic and enantiomerically enriched (scalemic) mixtures of secondary metabolites in their natural sources is a rare phenomenon. The unprecedent case of enantiomeric variations from levorotatory to dextrorotatory, and back to levorotatory, passing through an almost racemic mixture, was recently documented for areolal, the major epoxythymol of Piptothrix areolare. In an attempt to shed some light to understand the reasons for such an unusual behavior, herein, we evaluated this phenomenon by correlating the areolal enantiomeric purity with several environmental variables, including temperature, humidity, rain precipitation, wind speed, and radiation during over 1 year of the plant life cycle. The specific rotation and enantiomeric excess determined by 1 H-NMR-BINOL measurements provided the scalemic variations of areolal samples isolated from the roots collected from the same location along a 427-day period. The 1 H-NMR-BINOL methodology provided better sensitivity to enantiomeric variations than specific rotation measurements. Statistical data, including matrix correlation analysis, exploratory analysis by heatmap plotting, and the principal component analysis (PCA), suggested direct correlation of the scalemic variation with humidity, rain precipitation, and radiation variables with the best PCA explanation (78.4%) and noncritical or poor correlations in PCA explained in 60.2% and 48.4%, respectively. When variations in the optical activity parameter of any metabolite are observed, the search for scalemic mixtures along their host plant life cycle should be undertaken. Herein, this phenomenon could be associated with interactions with soil microorganisms and with evolutionary aspects of Piptothrix areolare which belongs to Asteraceae, one of the most successfully adaptable plant families.

Facility-based simulation as a programmatic tool for implementing a statewide contraceptive initiative.

BACKGROUND: Assessing implementation fidelity is highly recommended, but successful approaches can be challenging. Family Planning Elevated (FPE) is a statewide contraceptive initiative which partnered with 28 health clinics across Utah. To assess implementation fidelity, we developed in-situ high-fidelity simulation training to both determine clinic adherence to FPE and offer education to implementing teams. This study aimed to develop, pilot, and assess the use of simulation as a tool for measuring implementation fidelity. METHODS: We developed two simulation scenarios to determine implementation fidelity: one scenario wherein a client is seeking a new method of contraception and another in which the same client has returned to discontinue the method. Both simulations contained multiple aspects of program implementation (e.g., determining program eligibility). We then offered simulations to all FPE partner organizations. To assess simulation training as a tool for determining implementation fidelity, we developed strategies aligned with each aspect of an adapted RE-AIM framework, including pre-post surveys, acceptability and self-efficacy testing, a checklist for programmatic adherence, field notes, action planning and analysis of monitoring data. RESULTS: Fifteen clinical sites and 71 team members participated in the in-situ simulations. Assessment of the checklist showed that 90% of the clinics successfully demonstrated key program components, including person-centered counseling techniques such as sitting at the patient's level (95.8%); asking open-ended questions (100%); and explaining how to use the contraceptive method selected (91.7%). More than half of clinics fell short in programmatic areas including: confirmation that the FPE program covered same-day intrauterine device insertion (54.2%), and education on health risks associated with the selected contraceptive method (58.3%). After simulation, participants reported improved knowledge of how FPE works (p = < 0.001), increased ability to identify FPE-eligible clients (p = 0.02) and heightened self-efficacy in helping clients select a method (p = 0.03). Participants were satisfied with the simulations, with most (84.1%) reporting that the simulation exceeded their expectations. CONCLUSIONS: Highly-realistic in-situ family planning simulations are acceptable to participants, positively change knowledge and clinical team confidence, and can identify systems gaps in clinical care and program implementation. Simulation offers a reciprocal way of monitoring implementation fidelity of a family planning access initiative. TRIAL REGISTRATION: This project was determined to be exempt by the IRB of the University of Utah, the larger Family Planning Elevated program under which this pilot study was nested is registered at ClinicalTrials.gov Identifier: NCT03877757 .

Parasites in Periodontal Health and Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Periodontitis is an inflammatory disease triggered by the infection of the periodontal sulcus by microbes. Together with the abundant eubacterial microbiota, at least two parasites have often been identified: the amoeba Entamoeba gingivalis and the flagellate Trichomonas tenax. The role of these protists in the pathophysiology of periodontal disease remains to be deciphered. A high diversity in their measured prevalence, mainly due to methodological concerns, prevents further analysis of the aetiological link between these parasites and periodontitis. METHODS: To determine E. gingivalis and T. tenax prevalence in periodontal pockets as compared to healthy sulci, we have conducted a systematic review, searching 3 remote databases (Pubmed, LILACS, and Google Scholar), restricting to papers in which the diagnostic of the parasite was made using molecular methods. A total of 5 studies for E. gingivalis and 2 studies for T. tenax were included for the meta-analysis. RESULTS: In the periodontal pockets, the prevalence of parasites is 76.9% (95%-CI: 71.5-81.7%) for E. gingivalis and 38.6% (95%-CI: 27.2-50.0%) for T. tenax . Both parasites are more abundant in periodontal pockets as compared to healthy sulci, with a risk ratio of 3.96 (95%-CI: 1.57-9.98) for E. gingivalis and 21.82 (95%-CI: 6.71-70.96) for T. tenax . The two subtypes of E. gingivalis exhibited the same risk ratio: 3.30 (95%-CI: 1.27-8.55) for ST1 and 3.30 (95%-CI: 0.42-26.03) for ST2, but ST1 was more prevalent (70.6%, 95%-CI: 65.0-76.2%) than ST2 (43.9%, 95%-CI: 35.5-52.4%) in periodontal pockets. CONCLUSION: Altogether, the data show that parasites are more prevalent in the diseased than in the healthy. However, the differences in prevalence between species and subtypes call for more studies to be able to conclude about their individual contributions in the pathophysiology of periodontal diseases. The heterogeneity in prevalence estimation should be investigated further, in particular to make out biological from methodological heterogeneity.

Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence.

Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig-to-baboon xenotransplantation.

BACKGROUND: Nephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression of human CD47 (hCD47) on endothelial cells and podocytes isolated from hCD47 transgenic (Tg) swine markedly reduced phagocytosis by baboon and human macrophages. These observations led us to hypothesize that transplanting hCD47 Tg porcine kidneys could overcome the incompatibility of the porcine CD47-baboon SIRPα interspecies ligand-receptor interaction and prevent the development of proteinuria following KXTx. METHODS: Ten baboons received pig kidneys with vascularized thymic grafts (n = 8) or intra-bone bone marrow transplants (n = 2). Baboons were divided into three groups (A, B, and C) based on the transgenic expression of hCD47 in GalT-KO pigs. Baboons in Group A received kidney grafts with expression of hCD47 restricted to glomerular cells (n = 2). Baboons in Group B received kidney grafts with high expression of hCD47 on both glomerular and tubular cells of the kidneys (n = 4). Baboons in Group C received kidney grafts with low/no glomerular expression of hCD47, and high expression of hCD47 on renal tubular cells (n = 4). RESULTS: Consistent with this hypothesis, GalT-KO/hCD47 kidney grafts with high expression of hCD47 on glomerular cells developed minimal proteinuria. However, high hCD47 expression in all renal cells including renal tubular cells induced an apparent destructive inflammatory response associated with upregulated thrombospondin-1. This response could be avoided by a short course of weekly anti-IL6R antibody administration, resulting in prolonged survival without proteinuria (mean 170.5 days from 47.8 days). CONCLUSION: Data showed that transgenic expression of hCD47 on glomerular cells in the GalT-KO donor kidneys can prevent xenograft nephropathy, a significant barrier for therapeutic applications of xenotransplantation. The ability to prevent nephrotic syndrome following KXTx overcomes a critical barrier for future clinical applications of KXTx.

Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina.

Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotype distribution, HBV mutations and coinfections, which may have important clinical implications in public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations.

Extracellular vesicles and their associated miRNAs as potential prognostic biomarkers in chronic lymphocytic leukemia.

PURPOSE OF REVIEW: Many prognostic and predictive biomarkers have been proposed for chronic lymphocytic leukaemia (CLL). Here, we aim to discuss the evidence showing a prognostic potential for extracellular vesicles (EV) and their associated microRNAs (miRNAs). RECENT FINDINGS: EV are produced by several cells in the body as a physiological event; however, there is evidence suggesting that an elevated EV concentration is present in the circulation of CLL patients. Moreover, some studies have associated EV concentration with advanced Rai stage and unmutated CLL while others have demonstrated its potential as an independent prognostic factor for TTFT and OS. Finally, some studies have shown that CLL EV shared some dysregulated microRNAs with CLL cells and plasma. On the other hand, it was found that CLL EV has a distinctive microRNA expression profile. Until now, EV-associated miR-155 is the most studied miRNA. Despite methodological diversity and limitations in study design, unanimity in CLL EV concentration behaviour and miRNA content has been found.

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of Piptothrix areolare.

Since epoxythymols occur in Nature either as scalemic mixtures or as pure enantiomers, the knowledge of their chiral composition and of the absolute configuration (AC) of the dominant enantiomer turns out to be mandatory. This task has already been faced using 1,1-bis-2-naphthol (BINOL), as a chiral solvating agent in accurate 1H NMR quantifications to determine the enantiomeric ratio, and vibrational circular dichroism (VCD) to evidence the AC of the dominant enantiomer. We now explore the use of electronic circular dichroism (ECD) to determine the AC of an epoxythymol for which time-expensive DFT calculations would be required unless the AC of a related molecule is already known, from either VCD studies or single-crystal X-ray diffraction analysis, since one could correlate the ECD Cotton effect with the AC because in ECD only chromophores and their neighborhoods are evidenced. This method is now applied by using the epoxythymols from Piptothrix areolare. Known areolal (1) and 10-cinnamoyloxy-8,9-epoxythymol isobutyrate (2) were isolated from the roots, while known 7-acetoxy-10-cinnamoyloxy-8,9-epoxythymol isobutyrate (3) and 10-cinnamoyloxy-7-hydroxy-8,9-epoxythymol isobutyrate (4), as well as the new enantiopure 7-acetoxy-10-cinnamoyloxy-6-hydroxy-8,9-epoxythymol isobutyrate (5) and 10-cinnamoyloxy-8,9-epoxy-6-hydroxy-7-northymol isobutyrate (6), were obtained from the extract of the flowers. Chemical correlation of epoxythymols 1 and 3 was achieved. Compounds 1-4 were obtained as scalemic mixtures, and 5 and 6 as the pure (8S) enantiomers. In addition, the new 10-cinnamoyloxy-7-oxo-8,9-dehydrothymol isobutyrate (7) was isolated from the roots. The structures of 5-7 followed from NMR and HRMS data, while enantiomeric compositions of 1-6 were determined by 1H NMR-BINOL measurements. The AC determination for 2-6 was done by ECD using a sample of 1 to reference the ECD Cotton effect. In turn, the AC of 1 was determined by VCD and extensive DFT calculations. The ECD-BINOL methodology turned out to be some 500 times more sensitive than that combining VCD and 1H NMR-BINOL.

Identification and biochemical characterization of an ATP-dependent dihydroxyacetone kinase from Trypanosoma cruzi.

Dihydroxyacetone (DHA) can be used as an energy source by many cell types; however, it is toxic at high concentrations. The enzyme dihydroxyacetone kinase (DAK) has shown to be involved in DHA detoxification and osmoregulation. Among protozoa of the genus Trypanosoma, T. brucei, which causes sleeping sickness, is highly sensitive to DHA and does not have orthologous genes to DAK. Conversely, T. cruzi, the etiological agent of Chagas Disease, has two putative ATP-dependent DAK (TcDAKs) sequences in its genome. Here we show that T. cruzi epimastigote lysates present a DAK specific activity of 27.1 nmol/min/mg of protein and that this form of the parasite is able to grow in the presence of 2 mM DHA. TcDAK gene was cloned and the recombinant enzyme (recTcDAK) was expressed in Escherichia coli. An anti-recTcDAK serum reacted with a protein of the expected molecular mass of 61 kDa in epimastigotes. recTcDAK presented maximal activity using Mg+2, showing a Km of 6.5 µM for DHA and a K0.5 of 124.7 µM for ATP. As it was reported for other DAKs, recTcDAK activity was inhibited by FAD with an IC50 value of 0.33 mM. In conclusion, TcDAK is the first DAK described in trypanosomatids confirming another divergent metabolism between T. brucei and T. cruzi.

High sensitivity of invertebrate detritivores from tropical streams to different pesticides.

Freshwater organisms are often sensitive to pesticides, but their sensitivity varies across different taxa and with pesticide type and action mode, as shown by multiple acute toxicity tests. Such variability hampers predictions about how freshwater ecosystems may be altered by pesticide toxicity, which is especially critical for understudied areas of the world such as the tropics. Furthermore, there is little information about the sensitivity of some organisms that are key components of stream food webs; this is the case of litter-feeding detritivorous invertebrates, which contribute to the fundamental process of litter decomposition. Here, we examined the sensitivity of three common detritivores [Anchytarsus sp. (Coleoptera: Ptilodactylidae), Hyalella sp. (Amphipoda: Hyalellidae) and Lepidostoma sp. (Trichoptera: Lepidostomatidae)] to three pesticides commonly used (the insecticides bifenthrin and chlorpyrifos and the fungicide chlorothalonil) using acute (48 or 96 h) toxicity tests. Our study demonstrates that common-use pesticides provoke the mortality of half their populations at concentrations of 0.04-2.7 µg L-1. We found that all species were sensitive to the three pesticides, with the highest sensitivity found for chlorpyrifos. Additionally, we used the approach of species sensitivity distributions (SSD) to compare our study species with Daphnia magna and other temperate and tropical invertebrates. We found that the study species were among the most sensitive species to chlorpyrifos and chlorothalonil. Our results suggest that tropical detritivores merit special attention in ecological risk assessment of pesticides and highlight the need for accurate ecotoxicological information from ecologically relevant species in the tropics.

Validation of the QLQ-EN24 instrument for the assessment of health-related quality of life for women with endometrial cancer in México.

PURPOSE: The impact of disease activity or treatments on health-related quality of life (HRQL) is crucial in Oncology, but adequate instruments for this assessment are scarce. Our aim is to validate the Mexican-Spanish version of the QLQ-EN24 questionnaire to evaluate HRQL in women with endometrial cancer (EC). METHODS: This is a prospective study of Mexican women with EC, attending a single cancer centre, who responded the QLQ-C30 and QLQ-EN24 instruments; usual psychometric analysis were performed as well as the association of HRQL scales and relevant clinical data. Correlation analysis was performed with the Spearman's method, reliability analysis with the Cronbach's alpha, known-group comparisons with the Kruskal-Wallis test, and survival analysis with the Kaplan-Meier method and Log-rank test. RESULTS: One hundred and eighty-nine women with EC were assessed. Most functional scales reported high values, and most symptom scales, low. Questionnaire compliance rates were high and internal consistency tests demonstrated adequate convergent and divergent validity. Cronbach's α coefficients of the five multi-item scales the QLQ-EN24 instruments were from 0.659 to 0.887. Scales of the QLQ-C30 and QLQ-EN24 instruments distinguished among clinically distinct groups of patients, particularly based on serum albumin levels. The Urological symptoms, Gastrointestinal symptoms, Body image, Pelvic pain and Taste change scales were significantly associated with OS. CONCLUSION: The Mexican-Spanish version of the QLQ-EN24 questionnaire is reliable and valid for the assessment of HRQL in patients with EC and can be broadly used in multi-national clinical trials. However, conclusions derived from scales evaluating sexual function should be handled carefully.

Leprosy in the North and Northeast regions of Brazil: an integrated spatiotemporal approach.

OBJECTIVE: To analyse the spatiotemporal patterns of leprosy occurrence in the North and Northeast regions of Brazil from 2001 to 2017. METHODS: Mixed population-based ecological study with spatial and temporal trend analysis of epidemiological indicators based on new cases reported to the Information System for Notifiable Diseases of the Ministry of Health occurring in individuals residing in North and Northeast states of Brazil. RESULTS: A total of 396 987 new cases were analysed; 9.2% of these involved children <15 years of age, and 5.4% involved individuals with grade 2 disability (G2D). The Northeast region recorded 66.4% of the new cases. Most cases involved males between 15 and 59 years of age and of brown race/colour. The temporal trend showed a reduction in most of the indicators and study variables. The G2D rate did not have trends over time in the Northeast Region, in individuals 0-14 years of age, or in municipalities with 'very high' social vulnerability indexes. The spatial and spatiotemporal analysis showed the presence of hyperendemic foci with high detection risk involving municipalities in the states of Tocantins, Pará and Maranhão. CONCLUSION: Leprosy in the North and Northeast regions of Brazil persists as a critical public health problem. Temporal and spatiotemporal patterns identified in this study confirm that leprosy remains epidemiologically relevant in vulnerable areas. Surveillance and control interventions are needed in municipalities with low detection in the general population, in children and in individuals with G2D, to reduce late diagnosis.

OBJECTIF: Analyser les profils spatiotemporels de l'apparition des cas de lèpre dans les régions du nord et du nord-est du Brésil de 2001 à 2017. MÉTHODES: Etude écologique mixte basée sur la population avec analyse des tendances spatiales et temporelles des indicateurs épidémiologiques sur la base des nouveaux cas rapportés dans le Système d'Information sur les Maladies à Déclaration Obligatoire du Ministère de la Santé, survenant chez des individus résidant dans les Etats du nord et du nord-est du Brésil. RÉSULTATS: 396.987 nouveaux cas ont été analysés; 9,2% d'entre eux concernaient des enfants de moins de 15 ans et 5,4% concernaient des personnes avec un handicap de grade 2 (G2D). La région du nord-est a enregistré 66,4% des nouveaux cas. La plupart des cas concernaient des hommes âgés de 15 à 59 ans et de race/couleur noire. La tendance temporelle a montré une réduction dans la plupart des indicateurs et des variables de l'étude. Le taux de G2D n'a pas évolué au cours du temps dans la région du nord-est, chez les individus de 0 à 14 ans ou dans les municipalités avec des indices de vulnérabilité sociale "très élevés". L'analyse spatiale et spatiotemporelle a montré la présence de foyers hyper endémiques à risque élevé de détection impliquant des municipalités dans les Etats de Tocantins, Pará et Maranhão. CONCLUSION: La lèpre dans les régions du nord et du nord-est du Brésil persiste comme problème critique de santé publique. Les schémas temporels et spatiotemporels identifiés dans cette étude confirment que la lèpre reste épidémiologiquement importante dans les zones vulnérables. Des interventions de surveillance et de contrôle sont nécessaires dans les municipalités à faible détection dans la population générale et chez les enfants, ainsi que chez les personnes atteintes de G2D, afin de réduire le diagnostic tardif.

Transgenic expression of human CD47 reduces phagocytosis of porcine endothelial cells and podocytes by baboon and human macrophages.

BACKGROUND: Our initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury. METHODS: In order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages. RESULTS: We found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti-hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney. CONCLUSIONS: The similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig-to-human as well as a pig-to-baboon model.

Effect of the Tc13Tul antigen from Trypanosoma cruzi on splenocytes from naïve mice.

Trypanosoma cruzi, the etiological agent of Chagas disease, releases factors, including antigens from the trans-sialidase (TS) superfamily, which modulate the host immune responses. Tc13 antigens belong to group IV of TSs and are characterized by C-terminal EPKSA repeats. Here, we studied the effect of the Tc13 antigen from the Tulahuén strain, Tc13Tul, on primary cultures of splenocytes from naïve BALB/c mice. Recombinant Tc13Tul increased the percentage of viable cells and induced B (CD19+) lymphocyte proliferation. Tc13Tul stimulation also induced secretion of non-specific IgM and interferon-γ (IFN-γ). The same effects were induced by Tc13Tul on splenocytes from naïve C3H/HeJ mice. In vivo administration of Tc13Tul to naïve BALB/c mice increased non-specific IgG in sera. In addition, in vitro cultured splenocytes from Tc13Tul-inoculated mice secreted a higher basal level of non-specific IgM than controls and the in vitro Tc13Tul stimulation of these cells showed an enhanced effect on IgM and IFN-γ secretion. Our results indicate that Tc13Tul may participate in the early immunity in T. cruzi infection by favouring immune system evasion through B-cell activation and non-specific Ig secretion. In contrast, as IFN-γ is an important factor involved in T. cruzi resistance, this may be considered a Tc13Tul effect in favour of the host.