Publications by authors named "Milton Moraes"

167 Publications

Presence of Senescent and Memory CD8+ Leukocytes as Immunocenescence Markers in Skin Lesions of Elderly Leprosy Patients.

Front Immunol 2021 11;12:647385. Epub 2021 Mar 11.

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8 leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8 T lymphocytes, as well as reduced CD8CD28 cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in and gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.
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http://dx.doi.org/10.3389/fimmu.2021.647385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991105PMC
March 2021

Impact of Low Hemoglobin on Body Composition, Strength, and Redox Status of Older Hemodialysis Patients Following Resistance Training.

Front Physiol 2021 10;12:619054. Epub 2021 Mar 10.

Graduate Program of Physical Education, Catholic University of Brasilia, Brasília, Brazil.

Introduction: The purpose of this study was to: (i) investigate the effect of six months of resistance training (RT) on body composition, muscle strength, hematological patterns, and redox profile in maintenance hemodialysis (HD) patients, and; (ii) evaluate the effects of baseline concentrations of hemoglobin on the RT response.

Methods: One hundred fifty-seven subjects with chronic kidney disease (CKD) were randomly allocated into two groups: Control [CTL, ( = 76)] and RT ( = 81). A first visit was required for anamnesis and anthropometric measurements. Venous blood samples were collected at baseline and after twenty-four weeks of training in all patients for the analysis of clinical and redox balance markers. The RT program spanned six months and consisted of three sets of 8-12 repetitions with a rating of perceived exertion between 5 and 8 for three weekly sessions. Each exercise session was performed in twelve resistance exercises and it least for approximately 40 min.

Results: The main results demonstrated that RT decreased waist circumference by 3%, and decreased thiobarbituric reactive species (TBARS) by 28%. Moreover, RT increased handgrip strength by 28.4%, fat-free mass by 4.1%, hemoglobin by 5%, iron by 33.4%, glutathione by 121%, and Trolox equivalent antioxidant capacity by 14.2% ( < 0.05). Low hemoglobin concentrations impaired the effect of RT on fat-free mass gain.

Conclusion: Six months of RT in HD patients improved clinical parameters, such as hemoglobin, iron, body composition, and redox balance, while low hemoglobin concentration impaired exercise-benefits on fat-free mass in patients with CKD. These findings can contribute to a better clinical application of RT in the maintenance of hemodialysis patients.
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http://dx.doi.org/10.3389/fphys.2021.619054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987944PMC
March 2021

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load.

PLoS Negl Trop Dis 2021 Mar 9;15(3):e0009214. Epub 2021 Mar 9.

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Background: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.

Methodology/principal Findings: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.

Conclusions/significance: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.
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http://dx.doi.org/10.1371/journal.pntd.0009214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978340PMC
March 2021

Relapse in leprosy and drug resistance assessment in a tertiary hospital of the state of Espírito Santo, Brazil.

Rev Soc Bras Med Trop 2021 8;54. Epub 2021 Mar 8.

Fundação Oswaldo Cruz, Serviço de Hansenologia, Rio de Janeiro, RJ, Brasil.

Introduction: Leprosy recurrence is the reappearance of the disease after treatment with current schemes and discharged for cure and may have variable incubation periods.

Methods: This is a descriptive observational study of leprosy recurrence in Espírito Santo diagnosed between January 2018 and January 2020.

Results: One hundred and ninety-two cases were available, of which 30 were diagnosed with leprosy recurrence.

Conclusions: In 25 cases, the incubation period was 5-15 years after the first treatment, favoring bacillary persistence. In the remaining 5 cases, the disease had recurred after 15 years, pointing to reinfection as none of them exhibited drug resistance.
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http://dx.doi.org/10.1590/0037-8682-0375-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008889PMC
March 2021

Effects of dynamic and isometric resistance training protocols on metabolic profile in hemodialysis patients: a randomized controlled trial.

Appl Physiol Nutr Metab 2021 Mar 2. Epub 2021 Mar 2.

Universidade Catolica de Brasilia, 28106, Physical Education, Taguatinga, DF, Brazil.

To compare the effect of dynamic (DRT) and isometric (IRT) resistance training on glycemic homeostasis, lipid profile, and nitric oxide (NO) in hemodialysis (HD) patients. Patients were randomly distributed into three groups: control (CTL; n=65), DRT (n=65), and IRT (n=67). Patients were tested for fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, insulin resistance, lipid profile, leptin, insulin, adiponectin, C-reactive protein, and NO were assessed pre- and post-intervention period. Patients underwent to strength and body composition assessments. Subjects allocated in both DRT and IRT groups took part in a 24-week resistance training program, three times per week. Each training session was approximately one hour before dialysis and consisted of 3 sets of 8-12 repetitions at low intensity. Total workload was higher in the DRT as compared with the IRT. This heightened workload related to better glycemic homeostasis in HD patients as measured by regulation of insulin, adiponectin, and leptin, while improvement of triglycerides, free-fat mass, and muscle strength. Additionally, NO levels were increased on DRT group. NO was significantly correlated with glucose intolerance (r=-0.42, p=0.0155) and workload (r=0.46, p=0.0022). The IRT group only improved strength (p<0.05). 24-week of DRT improved glycemic homeostasis, lipid profile, and NO in HD patients. Although IRT seems to play an important role in increasing strength, DRT might be a better choice to promote metabolic adjustments in HD patients. Clinical Trial http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w/; nº RBR-3gpg5w Novelty Bullets: -DRT might be a better choice for metabolic improvements in CKD patients. -Exercise-training might treat metabolic imbalance in CKD patients.
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http://dx.doi.org/10.1139/apnm-2020-0900DOI Listing
March 2021

Effects of pre-dialysis resistance training on sarcopenia, inflammatory profile, and anemia biomarkers in older community-dwelling patients with chronic kidney disease: a randomized controlled trial.

Int Urol Nephrol 2021 Feb 20. Epub 2021 Feb 20.

Programa de Pós-Graduação em Educação Física, Universidade Católica de Brasília, Brasília, DF, Brazil.

Background: Sarcopenia and chronic kidney disease (CKD) have been associated with negative outcomes in older people, including inflammatory profile and anemia biomarkers.

Aims: To investigate the effects of pre-dialysis resistance training (RT) on sarcopenia, inflammatory profile, and anemia biomarkers in older patients with CKD.

Methods: A total of 107 patients with CKD (65.4 ± 3.7 years) were randomly allocated into four groups: sarcopenic RT (n = 37), non-sarcopenic RT (n = 20), sarcopenic control (n = 28), and non-sarcopenic control (n = 22). DXA and handgrip strength were used to classify sarcopenia according to EWGSOP-2. Treatment groups underwent a 24-week intervention with RT before each dialysis session, three times per week. Blood sample analysis for ferritin, hepcidin, iron availability, and inflammatory profile (TNFα, IL-6, and IL-10) was conducted. All-cause mortality was recorded over 5 years.

Results: Sarcopenic RT group increased iron availability after the intervention, while their counterparts decreased. Ferritin and hepcidin significantly decreased in sarcopenic RT group. RT elicited a reduction in both TNFα and IL-6, while increasing IL-10 in both intervention groups. The rate of sarcopenic subjects substantially decreased after the intervention period (from 37 to 17 in the RT group; p = 0.01). The proportion of deaths was higher (P = 0.033) for sarcopenic subjects (Controls 35.7% vs RT 29.7%) when compared to non-sarcopenic subjects (Controls 18% vs RT 10%). The proportion of deaths decreased according to the randomization group (X2 = 8.704; P < 0.1).

Conclusions: The 24-week RT intervention elicited a better sarcopenia status, better inflammatory profile, and improved anemia biomarkers. Sarcopenia was associated with higher mortality rate in older patients with CKD.
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http://dx.doi.org/10.1007/s11255-021-02799-6DOI Listing
February 2021

Overview of snakebite in Brazil: Possible drivers and a tool for risk mapping.

PLoS Negl Trop Dis 2021 Jan 29;15(1):e0009044. Epub 2021 Jan 29.

Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health of Brazil, Rio de Janeiro, RJ, Brazil.

Snakebite envenoming affects close to 2.7 million people globally every year. In Brazil, snakebites are reported to the Ministry of Health surveillance system and cases receive antivenom free of charge. There is an urgent need to identify higher risk areas for antivenom distribution, and to develop prevention activities. The objective of this study is to provide an overview of the epidemiological situation of snakebite envenoming in Brazil and explore possible drivers; as well as to create a flowchart tool to support decision-makers identify higher risk areas. An ecological-type study was carried out using data by municipality (2013-2017). Study parts: 1) Create a geocoded database and perform a descriptive and cluster analysis; 2) Statistical analysis to measure the association of snakebite and possible environmental and socioeconomic drivers; 3) Develop a flowchart to support decision-makers and the application of this tool in one state (Rio Grande do Sul) as an example. An average of 27,120 snakebite cases per year were reported at the country level. Clusters of municipalities with high numbers of snakebites are mostly found in the Amazon Legal Region. The negative binomial regression model showed association with the snakebite case count: the type of major habitat, tropical or non-tropical; temperature; percentage of urbanization; precipitation; elevation; GDP per capita; a weaker relation with forest loss; and with venomous snake richness. The state where the instrument was applied reported 4,227 snakebites in the period. Most municipalities were considered as medium risk and 56/496 as high risk according to the tool created. Snakebite cases are distributed across the entire country with the highest concentration in the Legal Amazon Region. This creates a complex situation both for better understanding of the association of environmental and socioeconomic factors with snakebites and for the distribution and maintenance of antivenom to remote areas. Research into types of antivenom with a longer shelf life without the need for refrigeration is needed.
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http://dx.doi.org/10.1371/journal.pntd.0009044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875335PMC
January 2021

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients.

Sci Rep 2021 Jan 21;11(1):1947. Epub 2021 Jan 21.

Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil.

Reduction in incidence has been associated with the introduction of novel approaches, like chemo/immune-prophylaxis. Incidence determined through follow-up cohort studies can evaluate the implementation of these innovative policies towards control and prevention. We have assessed the incidence in our contacts cohort over past 33 years, considering the effect of demographic and clinical variables. Survival analysis was used to estimate the risk of leprosy. A total of 9024 contacts were evaluated, of which 192 developed leprosy, resulting in an overall incidence of 1.4/1000 person-years. The multivariate analysis showed that the major risk factors were (i) contact from MB index cases and (ii) consanguinity (iii) intra household contact. Lower risk was detected for contacts with BCG scar who were revaccinated. There was a significant decrease in accumulated risk between the 2011-2019 period compared with 1987, probably linked to the improvement in laboratory tools to monitor contacts, thereby providing early diagnosis of contacts at intake and reduction of transmission. Our findings suggest that a combination of contact surveillance and tracing, adequate neurodermatological examination, and availability of molecular tools is highly effective in supporting early diagnosis, while a second dose of the BCG vaccination can exert extra protection.
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http://dx.doi.org/10.1038/s41598-021-81643-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820484PMC
January 2021

Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A.

Viruses 2021 Jan 12;13(1). Epub 2021 Jan 12.

Bio-Manguinhos/Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.

The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4 profile, robust T CD8 responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4 and CD8T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IRF9, OAS1, and RNASEL) as well as antibody levels. Furthermore, individuals with genotypes rs2430561 AT/AA, rs2069718 AG/AA (IFNG), and rs13237944 AC/AA (CLEC5A), exhibited higher expression of IFNG and CLEC5A, respectively. Together, we demonstrated that early IFN-γ and CLEC5A responses, associated with rs2430561, rs2069718, and rs13237944 genotypes, may be key mechanisms in the long-lasting immunity elicited by YF17DD.
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http://dx.doi.org/10.3390/v13010096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828179PMC
January 2021

Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts.

Infect Dis Poverty 2020 Dec 20;9(1):167. Epub 2020 Dec 20.

Núcleo de Pesquisa em Hansenologia, Universidade Federal de Juiz de Fora, Instituto de Ciências da Vida, Campus Governador Valadares, Rua São Paulo, 582 - Centro, Governador Valadares, MG, 30190-002, Brazil.

Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts.

Methods: The cross-sectional study enrolled 49 participants, including 19 patients and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated in the presence of Mycobacterium leprae bacilli. The cells were prepared for surface (CD4 and CD8) and intracytoplasmic cytokine staining (IFN-γ, IL-4 and IL-10). Multiple comparisons amongst groups were carried out by ANOVA, Kruskal-Wallis, Student T or Mann-Whitney test. Comparative analysis of categorical variables was performed by Chi-square. Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels.

Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-γ T-cell subsets along with IL-10 and IL-4 from CD4 T-cells, as compared to health Controls (Venn diagram report). Moreover, statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons, according to the data normality distribution. L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ, IL-10 and IL-4 produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10 and IL-4 T-cells with minor contribution of IFN-γ produced by CD4 T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-γ T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4.

Conclusions: Our data demonstrated that L(PB) displayed enhanced percentage of IFN-γ, IL-10 and IL-4 as compared to L(MB) that presented functional profile mediated by IL-10 and IL-4 T-cells and HHC(MB) exhibited enhanced frequency of IFN-γ T-cells, contrasting with HHC(PB). Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.
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http://dx.doi.org/10.1186/s40249-020-00763-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749990PMC
December 2020

Low-load resistance training with blood flow restriction prevent renal function decline: The role of the redox balance, angiotensin 1-7 and vasopressin.

Physiol Behav 2021 Mar 16;230:113295. Epub 2020 Dec 16.

Post-Graduate Program of Physical Education of Catholic University of Brasilia, Federal District, Brazil-71966-700. Electronic address:

Aims: We sought to investigate the effect of resistance training (RT) and low-load RT with moderate blood flow restriction (RT+BFR) on blood pressure, exercise pressor response, redox balance and vasoactive peptides, body composition and muscle strength in patients with stage two of chronic kidney disease (CKD).

Methods: We conducted a 6-month randomized controlled exercise intervention in 90 male and female hypertensive CKD patients (58±9 years with estimated glomerular filtration rate (eGFR; of 66.1 ± 1.2 mL/kg/1.73m). Participants were randomized to one of three groups (n = 30/group); control group (CTL), RT, and RT+BFR. RT and RT+BFR performed three weekly training sessions using similar periodization for six months (two-month mesocycles), but of different intensities.

Results: There was similarly effects between RT and RT+BFR in reducing systolic and diastolic blood pressure during daytime and 24hour period (RT: 10.4%; RT+BFR: 10.3% of decrease), fat mass, F-isoprostanes, asymmetric dimethylarginine (ADMA) and vasopressin (p<0.05 pre-vs post). Also promoted the increase of angiotensin 1-7, nitric oxide (NO), catalase, Trolox equivalent and muscle strength (p<0.05). Both training models attenuated the decline of estimated glomerular filtration rate (p<0.0001 vs CTL). However, only RT+BFR was associated with lower discomfort during exercise (p<0.0001 pre-vs post). Statistical significance was considered with p < 0.05.

Conclusion: These findings suggest low-load RT+BFR as a promising non-pharmacological strategy to control blood pressure, oxidative stress, vasoactive peptides, and consequently, attenuate the decrease of the eGFR.
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http://dx.doi.org/10.1016/j.physbeh.2020.113295DOI Listing
March 2021

Leprosy post-exposure prophylaxis: innovation and precision public health.

Lancet Glob Health 2021 01;9(1):e8-e9

Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil.

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http://dx.doi.org/10.1016/S2214-109X(20)30512-XDOI Listing
January 2021

Dynamic not isometric training blunts osteo-renal disease and improves the sclerostin/FGF23/Klotho axis in maintenance hemodialysis patients: a randomized clinical trial.

J Appl Physiol (1985) 2021 Feb 26;130(2):508-516. Epub 2020 Nov 26.

Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil.

This study compared the effectiveness of dynamic resistance training (DRT) versus isometric RT (IRT) on osteogenesis and hormonal mechanisms involved in maintenance hemodialysis (MHD) patients. One hundred and ninety-three MHD patients were randomized into three groups: control (CTL) ( = 60), DRT ( = 66), and IRT ( = 67). A first visit was required for an anamnesis to evaluate the number of medications, biochemical, and anthropometric measurements (dialysis adequacy, creatinine, urea, body mass, height, and body mass index). Grip strength, bone mineral density (BMD), and renal-bone markers were assessed pre- and postprotocol. The DRT and IRT training was 6 mo with a frequency of three times per week, on alternate days. Each training session consisted of three sets of 8 to 12 repetitions at lower and moderate intensities. Both training sessions were prescribed approximately 1 h prior to dialysis. Statistical significances were adopted with < 0.05. There was a greater dropout in the IRT group (24%) as compared with the DRT group (14%), which in turn had less adverse clinical effects (67%, 24%, and 61% for CTL, DRT, and IRT, respectively). DRT promoted gains in BMD in different body locations, in addition to increasing pro-osteogenic factors (Klotho and calcitriol) and reducing those related to bone loss, such as sclerostin, FGF23, and PTH. There was an improvement in Ca × PO for DRT, whereas these benefits did not occur in the IRT group ( < 0.05). These novel findings suggest that the DRT generates biopositive adaptations in bone tissue in MHD and can be used as a nonpharmacological strategy to improve BMD. This study shows, for the first time, the effect of dynamic and isometric resistance training on bone mineral density in hemodialysis patients, providing a new understanding of the possible participation of the sclerostin/FGF23/Klotho axis, vitD, PTH, and calcium × phosphate product in this process. However, isometric resistance training may not be sufficient to induce these benefits. Therefore, this study supports the potential therapeutic role of dynamic resistance training counteracting chronic kidney disease-mineral and bone disorder.
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http://dx.doi.org/10.1152/japplphysiol.00416.2020DOI Listing
February 2021

Association of MICA and HLA-B alleles with leprosy in two endemic populations in Brazil.

Int J Immunogenet 2021 Feb 5;48(1):25-35. Epub 2020 Nov 5.

Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case-control and a family-based study in two endemic populations in Brazil. MICA and HLA-B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR-SSOP-Luminex-based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi-square or Fisher's exact test together with a multivariate analysis. Family-based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002-HLA-B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA-A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA-B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA-B markers rs2596498 and rs2507992, and high LD (R  = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA-B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.
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http://dx.doi.org/10.1111/iji.12518DOI Listing
February 2021

Mycobacterium leprae induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO.

J Leukoc Biol 2020 Oct 11. Epub 2020 Oct 11.

Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

The enzyme IDO-1 is involved in the first stage of tryptophan catabolism and has been described in both microbicidal and tolerogenic microenvironments. Previous data from our group have shown that IDO-1 is differentially regulated in the distinctive clinical forms of leprosy. The present study aims to investigate the mechanisms associated with IDO-1 expression and activity in human monocyte-derived dendritic cells (mDCs) after stimulation with irradiated Mycobacterium leprae and its fractions. M. leprae and its fractions induced the expression and activity of IDO-1 in human mDCs. Among the stimuli studied, irradiated M. leprae and its membrane fraction (MLMA) induced the production of proinflammatory cytokines TNF and IL-6 whereas irradiated M. leprae and its cytosol fraction (MLSA) induced an increase in IL-10. We investigated if TLR2 activation was necessary for IDO-1 induction in mDCs. We observed that in cultures treated with a neutralizing anti-TLR2 antibody, there was a decrease in IDO-1 activity and expression induced by M. leprae and MLMA. The same effect was observed when we used a MyD88 inhibitor. Our data demonstrate that coculture of mDCs with autologous lymphocytes induced an increase in regulatory T (Treg) cell frequency in MLSA-stimulated cultures, showing that M. leprae constituents may play opposite roles that may possibly be related to the dubious effect of IDO-1 in the different clinical forms of disease. Our data show that M. leprae and its fractions are able to differentially modulate the activity and functionality of IDO-1 in mDCs by a pathway that involves TLR2, suggesting that this enzyme may play an important role in leprosy immunopathogenesis.
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http://dx.doi.org/10.1002/JLB.4A0320-188RDOI Listing
October 2020

Could sestrins 2 be the secret of resistance exercise benefiting dialytic patients?

Nephrol Dial Transplant 2020 12;35(12):2198-2199

Graduate Program in Physical Education, Catholic University of Brasilia, Federal District, Brazil.

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http://dx.doi.org/10.1093/ndt/gfaa212DOI Listing
December 2020

Molecular and serological characterization of occult hepatitis B among blood donors in Maputo, Mozambique.

Mem Inst Oswaldo Cruz 2020 23;115:e200006. Epub 2020 Sep 23.

Instituto Nacional de Saúde, Maputo, Mozambique.

Background: Occult hepatitis B virus (HBV) - characterized by the absence of detectable HBsAg in the presence of HBV DNA - represents a potential threat for blood safety.

Objectives: This study was conducted with the aim to investigate the serological and molecular characterization of occult HBV infection (OBI) among blood donors in Mozambique.

Methods: 1,502 blood donors were tested for HBsAg. All HBsAg-negative individuals were tested for HBV DNA. Antibodies against HBV core, surface and HBe antigen (anti-HBc, anti-HBs, HBeAg) were measured in HBV DNA positive individuals.

Findings: 1435 serum samples were HBsAg negative and 16 positive for HBV DNA, 14 confirmed to have OBI, corresponding to a frequency of 0.98%. Of the 14 OBI infections identified, 13/14 (92.8%) were positive for anti-HBc, 4/14 (28.5%) for anti-HBs, and no samples were reactive for HBeAg. Of the 14 OBI cases, nine samples (64.2%) were sequenced for the S/P region. Eight samples (88.9%) belonged to genotype A1 and one (11.1%) to genotype E. One escape mutation (T123A) associated with OBI and various amino acid substitutions for genotype A1 and E were observed.

Main Conclusions: Our results show the importance of using nucleic acid amplification test to detect occult hepatitis B infection in blood donors in Mozambique.
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http://dx.doi.org/10.1590/0074-02760200006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523502PMC
October 2020

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training.

Int J Sports Med 2021 Mar 18;42(3):283-290. Epub 2020 Sep 18.

Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil.

Aging muscle is prone to sarcopenia and its associated telomere shortening and increased oxidative stress. Telomeres are protected by a shelterin protein complex, proteins expressed in response to DNA damage. Aerobic exercise training has shown to positively modulate these proteins while aging, but the effects of resistance training are less clear. This investigation was to examine the role of dynamic and isometric RT on markers of senescence and muscle apoptosis: checkpoint kinase 2, 53 kDa protein, shelterin telomere repeat binding 1 and 2, DNA repair, telomere length and redox state in the quadriceps muscle. Fifteen 49-week-old male rats were divided into three groups: control, dynamic resistance training, and isometric resistance training. Dynamic and isometric groups completed five sessions per week during 16 weeks at low to moderate intensity (20-70% maximal load). Only dynamic group decreased expression of 53 kDa protein, proteins from shelterin complex, oxidative stress, and improved antioxidant defense. There was no difference among groups regarding telomere length. In conclusion, dynamic resistance training was more effective than isometric in reducing markers of aging and muscle apoptosis in elderly rats. This modality should be considered as valuable tool do counteract the deleterious effects of aging.
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http://dx.doi.org/10.1055/a-1231-5410DOI Listing
March 2021

Obese elderly with diabetes experience more pain and reduced quality of life compared to obese elderly with hypertension.

J Clin Transl Res 2020 Jun 12;5(5):253-259. Epub 2020 May 12.

Graduation Program in Gerontology and Graduation Program in Physical Education, Catholic University of Brasilia, Brasilia, Brazil.

Background And Aim: Growth of elderly population is a worldwide phenomenon that impacts public health. The objective of this study was to compare the pain levels, strength, and quality of life among elderly obese with diabetes or hypertension.

Materials And Methods: The study cohort comprised 52 obese elderly subjects with hypertension (n = 35) and diabetes (n = 17). The parameters measured were anthropometric features, handgrip strength, visual analog scale for pain, and quality of life using the World Health Organization questionnaire.

Results: The level of pain reported by obese hypertensive elderly subjects (5.3 ± 3.4) was lower than reported by obese diabetic elderly subjects (7.4 ± 2.4). Obese hypertensive elderly scored higher on quality of life (sensory functioning and past, present, and future [PPF] activities) than obese diabetic elderly. No differences were observed for the other parameters. Strength, pain, anthropometrics, and hemodynamics were not correlated to quality of life.

Conclusions: Obese elderly diabetics exhibit worse pain scores, sensorial abilities, and PPF activities than obese hypertensive elderly individuals.

Relevance For Patients: The difference in pain and quality of life aspects between obese elderly individuals with hypertension and diabetes should be accounted for in health-care programs designed for these individuals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453806PMC
June 2020

Blood Flow Restriction Training Blunts Chronic Kidney Disease Progression in Humans.

Med Sci Sports Exerc 2021 02;53(2):249-257

Graduate Program in Physical Education, Catholic University of Brasilia, Brasilia, BRAZIL.

Purpose: This study aimed to verify the effect of 6 months of periodized resistance training (RT) with and without blood flow restriction (BFR) in patients with stage 2 chronic kidney disease (CKD) on glomerular filtration rate (GFR), uremic parameters, cytokines, and klotho-fibroblast growth factor 23 (FGF23) axis.

Methods: A total of 105 subjects were randomized in three groups of 35 each: control (CTL), RT, and RT + BFR. A first visit was required for an anamnesis to evaluate the number of medications and anthropometric measurements (body weight, height, and body mass index). Muscle strength (one-repetition maximum) was assessed. Venous blood samples were collected at baseline and after 6 months of training in all patients for the analysis of markers of renal function and integrity, as well as for the determination of the inflammatory profile. Statistical significances were adopted with P < 0.05.

Results: Both training therapies attenuated the decline of GFR (P < 0.05). The majority of CTL patients declined to stage 3 CKD (88.5%), whereas fewer incidents were noted with RT (25.7%) and RT + BFR (17.1%). Improved uremic parameters as well as inflammation (IL-6, IL-10, IL-15, IL-17a, IL-18, and TNF-α) and klotho-FGF23 axis in RT and RT + BFR (P < 0.05) were observed. Monocyte chemoattractant protein 1 was not changed (P > 0.05) but presented a large effect size (Cohen's d), demonstrating a propensity for improvement.

Conclusion: Six months of periodized RT with and without BFR in patients with stage 2 CKD attenuated the progression of the disease by maintaining GFR, improving uremic parameters, cytokine profile regulation, and klotho-FGF23 axis.
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http://dx.doi.org/10.1249/MSS.0000000000002465DOI Listing
February 2021

Resistance training improves sleep quality, redox balance and inflammatory profile in maintenance hemodialysis patients: a randomized controlled trial.

Sci Rep 2020 07 16;10(1):11708. Epub 2020 Jul 16.

Graduate Program of Physical Education, Catholic University of Brasilia (USB), EPTC, QS07, LT1 s/n. Bloco G Sala 117, Águas Claras, Taguatinga, Brasília, DF, 71966-700, Brazil.

Patients in maintenance hemodialisys (HD) present sleep disorders, increased inflammation, unbalanced redox profiles, and elevated biomarkers representing endothelial dysfunction. Resistance training (RT) has shown to mitigate the loss of muscle mass, strength, improve inflammatory profiles, and endothelial function while decreasing oxidative stress for those in HD. However, the relation between those factors and sleep quality are inadequately described. The aim of this study was to verify the effects of 3 months of RT on sleep quality, redox balance, nitric oxide (NO) bioavailability, inflammation profile, and asymmetric dimethylarginine (ADMA) in patients undergoing HD. Our primary goal was to describe the role of RT on sleep quality. Our secondary goal was to evaluate the effect of RT on NO, metabolism markers, and inflammatory and redox profiles as potential mechanisms to explain RT-induced sleep quality changes. Fifty-five men undergoing maintenance hemodialysis were randomized into either a control (CTL, n = 25) and RT group (RTG; n = 30). Participants in the RT group demonstrated an improvement in sleep pattern, redox, inflammatory profiles, and biomarkers of endothelial function (NO and ADMA). This group also increased muscle strength (total workload in RT exercises of upper and lower limbs). These findings support that RT may improve the clinical status of HD patients by improving their sleep quality, oxidative and inflammatory parameters.
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http://dx.doi.org/10.1038/s41598-020-68602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367305PMC
July 2020

Reanalysis and integration of public microarray datasets reveals novel host genes modulated in leprosy.

Mol Genet Genomics 2020 Nov 13;295(6):1355-1368. Epub 2020 Jul 13.

Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Rio De Janeiro, 21040-360, Brazil.

Due to multiple hypothesis testing with often limited sample size, microarrays and other-omics technologies can sometimes produce irreproducible findings. Complementary to better experimental design, reanalysis and integration of gene expression datasets may help overcome reproducibility issues by identifying consistent differentially expressed genes from independent studies. In this work, after a systematic search, nine microarray datasets evaluating host gene expression in leprosy were reanalyzed and the information was integrated to strengthen evidence of differential expression for several genes. Our results are relevant in prioritizing genes and pathways for further investigation, whether in functional studies or in biomarker discovery. Reanalysis of individual datasets revealed several differentially expressed genes (DEGs) in accordance with original reports. Then, five integration methods (P value and effect size based) were tested. In the end, random-effects model and ratio association were selected as the main methods to pinpoint DEGs. Overall, classic pathways were found corroborating previous findings and validating this approach. Also, we identified some novel DEG involved especially with skin development processes (AQP3, AKR1C3, CYP27B1, LTB, VDR) and keratinocyte biology (CSTA, DSG1, KRT14, KRT5, PKP1, IVL), both still poorly understood in leprosy context. In addition, here we provide aggregated evidence towards some gene candidates that should be prioritized in further leprosy research, as they are likely important in immunopathogenesis. Altogether, these data are useful in better understanding host responses to the disease and, at the same time, provide a list of potential host biomarkers that could be useful in complementing leprosy diagnosis based on transcriptional levels.
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http://dx.doi.org/10.1007/s00438-020-01705-6DOI Listing
November 2020

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease.

Rev Soc Bras Med Trop 2020 3;53:e20190488. Epub 2020 Jul 3.

Hospital das Clínicas HCFMUSP, Instituto do Coração (InCor), Universidade de São Paulo, São Paulo, SP, Brasil.

Introduction: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy.

Methods: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment.

Results: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04).

Conclusions: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.
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http://dx.doi.org/10.1590/0037-8682-0488-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341830PMC
July 2020

Effects of resistance training on hepcidin levels and iron bioavailability in older individuals with end-stage renal disease: A randomized controlled trial.

Exp Gerontol 2020 10 4;139:111017. Epub 2020 Jul 4.

Catholic University of Brasilia, Federal District, Brazil.

Anemia is an inherent complication of older individuals with end-stage renal disease (ESRD) that is associated with inflammation which in turn is an important factor in the activation of hepcidin that contributes to the decrease in serum iron. Athough resistance training (RT) seems to reduce inflammation in ESRD, its influence on hepcidin and iron availability in hemodialysis patients is unclear. Therefore, the aim of this study was to exemine the effects of RT in on inflammatory profile, hepcidin, and iron status in older individuals with ESRD. End-stage renal disease patients (N: 157, age: 66.8 ± 3.6; body mass: 73 ± 15 body mass index:27 ± 3), were assigned to control (CTL n: 76) and exercise groups (RT n: 81). RT consisted of 24 weeks/3 days per week of a moderate intensity. There was an increase in the bioavailability of iron (ΔRT: 22.2; ΔCTL: -1 μg/dL, p < 0.0001), a decrease in hepcidin levels (ΔRT: -7.9; ΔCTL: 0.2 ng/mL, p < 0.0001),and an improvement of the inflammatory profile. These novel findings show that RT is a potential coadjuvant to reduce iron deficiency by decreasing the levels of hepcidin and pro-inflammatory markers in older patients undergoing hemodialysis.
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http://dx.doi.org/10.1016/j.exger.2020.111017DOI Listing
October 2020

Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes.

Nitric Oxide 2020 09 18;102:42-51. Epub 2020 Jun 18.

Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil. Electronic address:

Purpose: Studies have shown a positive influence of intense athletic training on several biomarkers of aging, but it remains unclear whether this influence is dependent of exercise-training-mode. This study compared redox balance, cytokine levels and biomarkers of aging between master sprinters and endurance athletes, as well as in young and middle-aged individuals as controls.

Methods: Participants were male master sprinters (SA, 50 ± 8.9yrs; n = 13) and endurance runners (EA, 53 ± 8.2yrs; n = 18) with remarkable athletic experience (~25yrs of practice), besides untrained young (YC, 22.7 ± 3.9yrs; n = 17) and age-matched controls (MC, 45.5 ± 9.8yrs; n = 12). Anamnesis, anthropometrics, biomarkers of aging, inflammation status and oxidative stress parameters were analyzed in all participants.

Results: An increased pro-oxidant activity (elevated protein carbonyl; isoprostanes and 8-OHdG) was observed for MC in comparison to remaining groups (p < 0.05). However, SA presented a better antioxidant capacity than both MC and EA, while nitrite/nitrate (NO) availability was higher for EA and lower for the MC (p < 0.05). Both groups of athletes presented a better anti-inflammatory status than MC (increased IL-10 and lowered IL-6, sIL-6R, sTNF-RI), but worse than YC (increased TNF-α, sTNF-RI, and sIL-6R) (p < 0.05). Telomere length was shorter in MC, which also had lower levels of irisin and klotho, and elevated FGF-23 (p < 0.05). ADMA levels were higher in MC and SA, while irisin was lower in EA when compared to SA and YC (p < 0.05).

Conclusion: Master athletes presented better redox balance and inflammatory status, with decreased biomarkers of aging compared to control. Regarding exercise mode, a better NO- profile, as a marker of endothelial function, was observed for EA, whereas SA had a better redox balance, cytokines profile and attenuated biomarkers of aging.
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http://dx.doi.org/10.1016/j.niox.2020.05.004DOI Listing
September 2020

Population Genomics of Reveals a New Genotype in Madagascar and the Comoros.

Front Microbiol 2020 11;11:711. Epub 2020 May 11.

Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, . In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the strains circulating in Madagascar ( = 30) and the Comoros ( = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.
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http://dx.doi.org/10.3389/fmicb.2020.00711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233131PMC
May 2020

Ultra-sensitive detection of Mycobacterium leprae: DNA extraction and PCR assays.

PLoS Negl Trop Dis 2020 05 26;14(5):e0008325. Epub 2020 May 26.

Laboratório de Hanseníase, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brazil.

Leprosy urgently needs a precise and early diagnostic tool. The sensitivity of the direct (bacilli staining, Mycobacterium leprae DNA) and indirect (antibody levels, T cell assays) diagnostics methods vary based on the clinical form. Recently, PCR-based M. leprae DNA detection has been shown to differentially diagnose leprosy from other dermatological conditions. However, accuracy can still be improved, especially for use with less invasive clinical samples. We tested different commercial DNA extraction kits: DNeasy Blood & Tissue, QIAamp DNA Microbiome, Maxwell 16 DNA Purification, PowerSoil DNA Isolation; as well as in-house phenol-chloroform and Trizol/FastPrep methods. Extraction was performed on M. leprae-infected mouse footpads and different clinical samples of leprosy patients (skin biopsies and scrapings, lesion, oral and nasal swabs, body hair, blood on FTA cards, peripheral whole blood). We observed that the Microbiome kit was able to enrich for mycobacterial DNA, most likely due the enzymatic digestion cocktail along with mechanical disruption involved in this method. Consequently, we had a significant increase in sensitivity in skin biopsies from paucibacillary leprosy patients using a duplex qPCR targeting 16S rRNA (M. leprae) and 18S rRNA (mammal) in the StepOnePlus system. Our data showed that the presence of M. leprae DNA was best detected in skin biopsies and skin scrapings, independent of the extraction method or the clinical form. For multibacillary patients, detection of M. leprae DNA in nasal swabs indicates the possibility of having a much less invasive sample that can be used for the purposes of DNA sequencing for relapse analysis and drug resistance monitoring. Overall, DNA extracted with the Microbiome kit presented the best bacilli detection rate for paucibacillary cases, indicating that investments in extraction methods with mechanical and DNA digestion should be made.
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http://dx.doi.org/10.1371/journal.pntd.0008325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274454PMC
May 2020

Association of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population.

PLoS Negl Trop Dis 2020 05 20;14(5):e0008247. Epub 2020 May 20.

Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.

Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, which affects skin and peripheral nerves. Polymorphisms in genes associated with autophagy, metabolism, innate and adaptive immunity confer susceptibility to leprosy. However, these associations need to be confirmed through independent replication studies in different ethnicities. The population from Amazon state (northern Brazil) is admixed and it contains the highest proportion of Native American genetic ancestry in Brazil. We conducted a case-control study for leprosy in which we tested fourteen previously associated SNPs in key immune response regulating genes: TLR1 (rs4833095), NOD2 (rs751271, rs8057341), TNF (rs1800629), IL10 (rs1800871), CCDC122/LACC1 (rs4942254), PACRG/PRKN (rs9356058, rs1040079), IFNG (rs2430561), IL6 (rs2069845), LRRK2 (rs7298930, rs3761863), IL23R (rs76418789) and TYK2 (rs55882956). Genotyping was carried out by allelic discrimination in 967 controls and 412 leprosy patients. Association with susceptibility was assessed by logistic regression analyses adjusted for the following covariates: gender, age and ancestry. Genetic ancestry was similar in case and control groups. Statistically significant results were only found for IFNG and NOD2. The rs8057341 polymorphism within NOD2 was identified as significant for the AA genotype (OR = 0.56; 95% CI, 0.37-0.84; P = 0.005) and borderline for the A allele (OR = 0.76; 95% CI, 0.58-1.00; P = 0.053) and carrier (OR = 0.76; 95% CI, 0.58-1.00; P = 0.051). The rs2430561 SNP in IFNG was associated with disease susceptibility for the AT genotype (OR = 1.40; 95% CI, 1.06-1.85; P = 0.018) and carrier (OR = 1.44; 95% CI, 1.10-1.88; P = 0.008). We confirmed that NOD2 and IFNG are major players in immunity against M.leprae in the Amazon ethnic admixed population.
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http://dx.doi.org/10.1371/journal.pntd.0008247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239438PMC
May 2020

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil

A case of rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in was also detected. Clinical improvement was achieved using an alternative therapy.
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http://dx.doi.org/10.1128/AAC.00330-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318023PMC
June 2020

Faster and Healthier: Relationship between Telomere and Performance in Master Athletes.

Int J Sports Med 2020 May 11;41(5):339-344. Epub 2020 Feb 11.

Graduate Program in Physical Education, Catholic University of Brasilia - UCB, Brasília, Brazil.

Aging is associated with increased oxidative stress, chronic inflammation, and decreased telomere length (TL). However, the lifestyle of master athletes can lead to a reduced risk of these conditions, and thus attenuates aging and performance deterioration. We aimed to analyze the relationships between TL and relative performance (RP), and their relation to adiposity, oxidative stress, and inflammation in endurance (END) and sprint/power (SPW) master athletes (MAs). Twenty-two world-class MAs visited the laboratory for anamnesis, anthropometrics, and blood sampling. Inflammatory and oxidative stress parameters were assessed using commercial kits. Relative TL was determined in leukocytes through qPCR analyses. A positive association was observed between RP and TL in both groups (SPW: 0.641; END: 0.685) and the whole sample (0.594). The IL6/IL10 ratio presented an inverse correlation with RP in the whole sample (-0.580). Body mass index also demonstrated a negative correlation with TL for the END group (-0.690) and the whole sample analysis (-0.455). Moreover, the IL6/IL10 ratio was negatively associated with strength/power training hours (=-0.464), whereas the CAT/TBARS ratio was negatively associated with aerobic training hours (-0.482). In conclusion, TL of MAs was associated with RP regardless of the training model (endurance or sprint/power), and inflammation and adiposity were associated with shorter telomeres.
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http://dx.doi.org/10.1055/a-1088-5279DOI Listing
May 2020