Correction: Pontes do Nascimento et al. Synthesis of Mesoporous Zn1-xMxAl2O4 Substituted by Co2+ and Ni2+ Ions and Application in the Photodegradation of Rhodamine B. Materials 2020, 13, 2150.

In the original publication [...].

Effects of a high-fat diet on the bone structure of Wistar rats: a systematic review.

CONTEXT: Saturated fats found in diets known as high-fat, cafeteria, or Western diets appear to have a negative effect on bone structure; however, few studies have focused on investigating this association, and the data available in the literature remain controversial. OBJECTIVE: The aim of the current review was to investigate the effects of a high-fat dietary intake on the bone structure of Wistar rats. DATA SOURCES: A search for articles was carried out in the Pubmed/MEDLINE, Web of Science, Embase, and Scopus databases. DATA EXTRACTION: In total, 447 articles were found in the initial search; 5 articles were included in the systematic review, after application of the exclusion criteria. DATA ANALYSIS: The review was guided by the PICOS strategy and based on the PRISMA protocol for animal reviews. CONCLUSION: High-fat diets appear to affect bone structure of Wistar rats. Diet composition and exposure time are the factors determining the strength of the effect.

The FOXP3-924 A/G Single Nucleotide Polymorphism May Be Associated with Predictive Factors for Human T Lymphotropic Virus 1 Associated Myelopathy.

Human T lymphotropic virus 1 (HTLV-1) is a retrovirus associated with inflammatory diseases, including HTLV-1-associated myelopathy (HAM), and host genetic factors may be involved in disease evolution. The forkhead Box P3 (FOXP3) transcription factor is linked to homeostasis of the immune system, and the presence of polymorphisms in the promoter region of the FOXP3 gene should reflect its expression levels and consequent activation of regulatory T cells, which may contribute to severe inflammatory disorders, such as HAM. This study evaluated the rs2232365 polymorphism (-924 A/G) located in the promoter region of the FOXP3 gene and its association with HAM. Forty DNA samples from asymptomatic carriers and 25 samples from HAM patients were used, in addition to 130 control samples. The polymorphism was genotyped by conducting real-time polymerase chain reaction (PCR) (quantitative PCR [qPCR]) on extracted DNA. The proviral loads (PVLs) and CD4+ and CD8+ T lymphocyte counts were determined by qPCR and FACSCalibur flow cytometry, respectively. The PVLs, CD4+ T lymphocyte concentrations, and tumor necrosis factor-α dosages were considered predictive factors of the clinical profiles of HTLV-1 infection, all of which had higher levels in the HAM group. Carriers of the GG genotype for the polymorphism rs2232365 had high PVLs and CD4+ T lymphocyte concentrations.

Hematological changes in human lymphotropic-T virus type 1 carriers.

The human T-lymphotropic virus type 1 (HTLV-1), isolated in 1980, causes T-cell leukemia/lymphoma in adulthood, a type of lymphoproliferative disease, and chronic HTLV-1-associated myelopathy, a disease that causes paralysis of the lower limbs, which occur in about 5% of cases in this viral infection. This study aimed to establish the hematological profile of patients with HTLV-1 infection in Belém do Pará, describing the hematological parameters under study, estimating the frequency of lymphocytic atypical, and associating the hematological profile with diseases and symptoms. Hematologic data from 202 individuals were analyzed, including 87 HTLV-1 infected individuals and 115 non-HTLV-1 infected individuals as a control group, composed, at a great part, of relatives of the infected. The seroprevalence of HTLV-1 infection was observed in 71.3% of female individuals, with predominance in the group older than 50 years (44.8%). The analysis of hematological parameters showed a significant difference in the counts of the segmented cells (p = 0.0303) and eosinophils (p = 0.0092) in HTLV-1 carriers. Lymphocytic atypical was a finding present only in HTLV-1 carriers (p = 0.0001). There was no high frequency in the leukocyte counts of those infected by HTLV-1 not among them concerning a significant increase or decrease. It is concluded that HTLV-1 infection is prominent in women over 50 years old. The hematological profile of those infected shows a reduction of segmented cells, an increase of eosinophils, and the presence of atypical lymphocytes. The hematological profile of the HTLV-1 carrier should always be evaluated to identify early some diseases associated with the infection.

Dietary Intake of Flaxseed Oil since Early Stages of Life Promotes Femur Quality in Male Rats.

BACKGROUND: Flaxseed oil (FO) is an alpha linolenic acid source important for growth and body development. However, there is little literature on the role of FO in critical stages of bone development and formation. OBJECTIVE: This study evaluated the influence of a diet containing FO on rat femurs. METHODS: After birth, mothers and pups were divided into control and flaxseed groups (n = 6 pups each) fed diets containing 7% soybean oil (C) or 7% FO. At 21 days, pups were weaned and separated from the mothers, and control or experimental diets were continued. At 67 days, the following were analyzed: osteocalcin and osteoprotegerin (OPG) levels, bone mineral density (BMD) and content, and bone area; the dimension, BMD, head radiodensity, and biomechanical proprieties of the right femur; and histomorphometric parameters of the left femur. RESULTS: Compared to the C group, the FO group presented (p < 0.05) a lower body mass (-3.7%) and medullary area (-10.1%) and higher osteocalcin (+36.7%), OPG (+52.5%), femur width (+3.8%), absolute mass (+2.3%), femur BMD (+3.6%), head radiodensity (+6.1%), maximum force (+7.4%), breaking strength (+17.3), and cortical thickness (+7.0). CONCLUSION: The FO diet contributed to femur quality in healthy male Wistar rats.

Adding Prior Information in FWI through Relative Entropy.

Full waveform inversion is an advantageous technique for obtaining high-resolution subsurface information. In the petroleum industry, mainly in reservoir characterisation, it is common to use information from wells as previous information to decrease the ambiguity of the obtained results. For this, we propose adding a relative entropy term to the formalism of the full waveform inversion. In this context, entropy will be just a nomenclature for regularisation and will have the role of helping the converge to the global minimum. The application of entropy in inverse problems usually involves formulating the problem, so that it is possible to use statistical concepts. To avoid this step, we propose a deterministic application to the full waveform inversion. We will discuss some aspects of relative entropy and show three different ways of using them to add prior information through entropy in the inverse problem. We use a dynamic weighting scheme to add prior information through entropy. The idea is that the prior information can help to find the path of the global minimum at the beginning of the inversion process. In all cases, the prior information can be incorporated very quickly into the full waveform inversion and lead the inversion to the desired solution. When we include the logarithmic weighting that constitutes entropy to the inverse problem, we will suppress the low-intensity ripples and sharpen the point events. Thus, the addition of entropy relative to full waveform inversion can provide a result with better resolution. In regions where salt is present in the BP 2004 model, we obtained a significant improvement by adding prior information through the relative entropy for synthetic data. We will show that the prior information added through entropy in full-waveform inversion formalism will prove to be a way to avoid local minimums.

Post-weaning protein malnutrition induces myocardial dysfunction associated with oxidative stress and altered calcium handling proteins in adult rats.

Hypercaloric low-protein diet may lead to a state of malnutrition found in the low-income population of Northeastern Brazil. Although malnutrition during critical periods in the early life is associated with cardiovascular diseases in adulthood, the mechanisms of cardiac dysfunction are still unclear. Here we studied the effects of post-weaning malnutrition due to low protein intake induced by a regional basic diet on the cardiac contractility of young adult rats. In vivo arterial hemodynamic and in vitro myocardial contractility were evaluated in 3-month-old rats. Additionally, protein content of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), total phospholamban (PLB) and phosphorylated at serine 16 (p-Ser(16)-PLB), α2-subunit of the Na(+)/K(+)-ATPase (α2-NKA), and Na(+)/Ca(2+) exchanger (NXC) and in situ production of superoxide anion (O2(-)) were measured in the heart. Blood pressure and heart rate increased in the post-weaning malnourished (PWM) rats. Moreover, malnutrition decreased twitch force and inotropic responses of the isolated cardiac muscle. Protein expression of SERCA, PLB/SERCA, and p-Ser(16)-PLB/PLB ratios and α2-NKA were decreased without changing NCX. The contraction dependent on transsarcolemmal calcium influx was unchanged but responsiveness to Ca(2+) and tetanic peak contractions were impaired in the PWM group. Myocardial O2(-) production was significantly increased by PWM. Our data demonstrated that this hypercaloric low-protein diet in rats is associated with myocardial dysfunction, altered expression of major calcium handling proteins, and increased local oxidative stress. These findings reinforce the attention needed for pediatric care, since chronic malnutrition in early life is related to increased cardiovascular risk in adulthood. Graphical Abstract.

Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. METHODS: This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). CONCLUSIONS: Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.

Beverages Rich in Resveratrol and Physical Activity Attenuate Metabolic Changes Induced by High-Fat Diet.

Consumption of saturated fat causes deleterious effects on health, which could be minimized through physical activity and foods with functional characteristics consumption. The aim of the study was to evaluate the beverage rich in resveratrol consumption and physical exercise in gut microbiota, body composition, lipid peroxidation, interleukin-6 (IL6) concentration and systolic blood pressure (SBP) of rats to the high-fat diet. Wistar rats were fed with control diet, high-fat diet (HFD), HFD and 15 mL solution of resveratrol, HFD and 15 mL of grape juice, HFD and 10 mL of red wine. All animals performed the physical training protocol five days a week. Grape juice and red wine composition were analyzed, SBP, body mass, consumption, adiposity and body composition, gut microbiota, lipid peroxidation and inflammation were evaluated. The grape juice (114.8 ± 22.5 mmHG) and red wine (129 ± 15.8 mmHg) groups showed lower SBP when compared to HFD (216.8 ± 20.6 mmHg) (p < 0.0001). The grape juice group (GJG) (39.1 ± 7) had a higher number of microbiota bands DNA when compared to the other groups (p = 0.002). The GJG (33.7 ± 6.7 pg/mL) presented lower concentration IL6 when compared to high-fat group (47.3 ± 16 pg/mL) (p = 0.003). GJG (4.7 ± 1.2 nmol/L) presented a lower concentration of TBARS when compared to control group (6.1 ± 1.4 nmol/L) and resveratrol group (6.6 ± 0.9 nmol/L), and the red wine group (7.4 ± 1.2 nmol/L) had a higher concentration of TBARS when compared to control group and GJG (p = 0.0001). The consumption of these beverages, especially grape juice, together with physical exercise, was able to promote beneficial changes even in the presence of a HFD.

Chitosan Membrane Containing Copaiba Oil (Copaifera spp.) for Skin Wound Treatment.

The interaction of copaiba oil in the polymer matrix of chitosan can produce a favorable synergistic effect and potentiate properties. Indeed, the bioactive principles present in copaiba oil have anti-inflammatory and healing action. In the present work, chitosan membranes containing different contents of copaiba oil copaíba (0.1, 0.5, 1.0 and 5.0% (v/v)) were for the first time investigated. The membranes were developed by the casting method and analyzed for their morphology, degree of intumescence, moisture content, contact angle, Scanning Electron Microscope, and X-ray diffractometry. These chitosan/copaiba oil porous membranes disclosed fluid absorption capacity, hydrophilic surface, and moisture. In addition, the results showed that chitosan membranes with the addition of 1.0% (v/v) of copaiba oil presented oil drops with larger diameters, around 123.78 µm. The highest fluid absorption indexes were observed in chitosan membranes containing 0.1 and 0.5% (v/v) of copaiba oil. In addition, the copaiba oil modified the crystalline structure of chitosan. Such characteristics are expected to favor wound treatment. However, biological studies are necessary for the safe use of chitosan/copaiba oil membrane as a biomaterial.

An objective function for full-waveform inversion based on frequency-dependent offset-preconditioning.

Full-waveform inversion (FWI) is a powerful technique to obtain high-resolution subsurface models, from seismic data. However, FWI is an ill-posed problem, which means that the solution is not unique, and therefore the expert use of the information is required to mitigate the FWI ill-posedness, especially when wide-aperture seismic acquisitions are considered. In this way, we investigate the multiscale frequency-domain FWI by using a weighting operator according to the distances between each source-receiver pair. In this work, we propose a weighting operator that acts on the data misfit as preconditioning of the objective function that depends on the source-receiver distance (offset) and the frequency used during the inversion. The proposed operator emphasizes information from long offsets, especially at low frequencies, and as a consequence improves the update of deep geological structures. To demonstrate the effectiveness of our proposal, we perform numerical simulations on 2D acoustic Marmousi2 case study, which is widely used in seismic imaging tests, considering three different scenarios. In the first two ones, we have used an acquisition geometry with a maximum offset of 4 and 8 km, respectively. In the last one, we have considered all-offsets. The results show that our proposal outperforms similar strategies, for all scenarios, providing more reliable quantitative subsurface models. In fact, our inversion result has the lowest error and the highest similarity to the true model than similar approaches.

Fractional Order Pole Placement for a buck converter based on commensurable transfer function.

In this work, a novel methodology for tuning fractional order controller, so-called fractional order pole placement (FOPP) is proposed. The proposed methodology extends classical (integer order) pole placement technique, using commensurable transfer functions for representing fractional order controllers and placing the fractional dominant poles within an extended stability region based on three terms fractional transfer functions. The designed fractional order controller can be digitally implemented by using the Oustaloup integer approximation of the fractional order dynamics with Hankel model reduction. The proposed FOPP is used to design fractional order controllers for a DC/DC buck converter. The experimental tests include comparisons between the proposed FOPP and other tuning methodologies for integer and fractional order controllers for the DC/DC buck converter that is subject to load, parametric, and load variations. Integral indices are computed to aid the assessment of the control strategies with respect to the robustness, performance specification compliance, and control effort. The results show that the proposed method outperforms the other approaches when occurs the variations.

CD49d Is Upregulated in Circulating T Lymphocytes from HTLV-1-Infected Patients.

INTRODUCTION: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy associated with an inflammation of the central nervous system (CNS), being characterized by perivascular infiltration of inflammatory cells. HTLV-1-infected cells have the capacity to migrate through endothelial layers by enhancing adhesion receptor expression and corresponding ligands. T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cell migration and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. METHODS: Herein we studied the expression of 3 integrin alpha chains (CD49d, CD49e, and CD49f) on the membrane of T-cell subsets in patients infected by HTLV-1, both HAM/TSP patients and oligo/asymptomatic subjects who were asymptomatic or presented slight manifestations related to the virus infection. RESULTS: We observed higher peripheral blood frequency of CD49dhiCD4+ and CD49dhiCD8+ T cells in HTLV-1-infected patients. CONCLUSION: Our findings suggest that the increased expression of adhesion molecules, such as CD49d on T lymphocytes from HTLV-1-infected patients may contribute to the pathogenesis of the disease, in both oligo/asymptomatic and HAM/TSP-infected subjects. Accordingly, it is conceivable that there is a potential use of CD49d as target for a therapeutic approach aiming at blocking migration of activated T cells from HTLV-1-infected patients into the CNS, thus avoiding the progression to HAM/TSP.

The SAMHD1 rs6029941 (A/G) Polymorphism Seems to Influence the HTLV-1 Proviral Load and IFN-Alpha Levels.

SAMHD1, a host dNTPase, acts as a retroviral restriction factor by degrading the pool of nucleotides available for the initial reverse transcription of retroviruses, including HTLV-1. Polymorphisms in the SAMDH1 gene may alter the enzymatic expression and influence the course of infection by the virus. The present study investigated the effect of polymorphisms on HTLV-1 infection susceptibility and on progression to disease in 108 individuals infected by HTLV-1 (47 symptomatic and 61 asymptomatic) and 100 individuals in a control group. SAMHD1 rs6029941 (G/A) genotyping and HTLV-1 proviral load measurements were performed using real-time PCR and plasma IFN-α was measured by ELISA. Polymorphism frequency was not associated with HTLV-1 infection susceptibility or with the presence of symptoms. The proviral load was significantly higher in symptomatic individuals with the G allele (p = 0.0143), which presented lower levels of IFN-α (p = 0.0383). SAMHD1 polymorphism is associated with increased proviral load and reduced levels of IFN-α in symptomatic patients, and may be a factor that contributes to the appearance of disease symptoms.

Activated carbon obtained from amazonian biomass tailings (acai seed): Modification, characterization, and use for removal of metal ions from water.

Acai seed was used herein as an Amazon biomass waste for the synthesis of activated and modified carbon in order to find a possible use for the large volume of residues generated during the processing of this fruit and to add value to this residue. Activated carbon materials were used to remove Pb2+, Fe2+, and Mg2+ metal ions from water. The efficiency of removal of these ions by the acai seed activated carbon was compared with that by commercial activated carbon. Activated carbon materials were prepared by carbonization and chemical activation using two KOH impregnation ratios, namely 1:1 (ACK1) and 5:1 (ACK5), by mass. These samples were modified by treatment with nitric acid under microwave heating (ACK1-M) and (ACK5-M), respectively. The result of the elemental analysis indicated that this biomass has carbon and sulfur contents of 43.29% and 0.10% wt, respectively. The textural parameters showed that the obtained activated carbon samples presented high surface areas between 1462 and 2774 m2 g-1. Raman analysis revealed the different degrees of graphitization of the activated carbon materials. Boehm titration identified the presence of phenolic, carboxylic, and lactonic groups in samples that were confirmed by Fourier transform infrared spectroscopy. In the metal adsorption tests, ACK5-M showed better removal efficiency, reaching 86% removal for Pb2+, 69% for Fe2+, and 8% for Mg2+in 1 h of contact time; these results were superior to those obtained for commercial carbon. The results indicated that acai seed can be used for the production of activated carbon and can also be used for metal removal.

Acetylation of Eugenol over 12-Molybdophosphoric Acid Anchored in Mesoporous Silicate Support Synthesized from Flint Kaolin.

A new prepared catalyst, 12-molybdophosphoric acid (HPMo) anchored to the mesoporous aluminosilicate AlSiM, synthesized from Amazon kaolin, was characterized and used as a heterogeneous acid catalyst for the production of eugenyl acetate by acetylation of eugenol with acetic anhydride. The effect of various reaction parameters, such as catalyst concentration, eugenol/acetic anhydride molar ratio, temperature and reaction time, was studied to optimize the conditions of maximum conversion of eugenol. The kinetics studies showed that in eugenol acetylation, the substrate concentration follows a first order kinetics. The results of activation energy was 19.96 kJ mol-1 for HPMo anchored to AlSiM. The reuse of the catalyst was also studied and there was no loss of catalytic activity after four cycles of use (from 99.9% in the first cycle to 90% in the fifth cycle was confirmed), and an excellent stability of the material was observed. Based on catalytic and kinetic studies, HPMo anchored to AlSiM is considered an excellent catalyst.

Antioxidant action of alpha lipoic acid on the testis and epididymis of diabetic rats: morphological, sperm and immunohistochemical evaluation.

INTRODUCTION: Chronic hyperglycemia is caused by diabetes mellitus-committed genital morphophysiology, and oxidative stress is one of the main factors involved in this process. Alpha lipoic acid (ALA) can prevent metabolic and morphological changes in diabetic individuals. OBJECTIVES: In present study, we evaluated the effects of regular ALA consumption on the spermatogenesis and histoarchitecture in the male genital system of diabetic rats. MATERIALS AND METHODS: Thirty-two Wistar rats were divided into groups: Control (CG); Diabetic Control (DCG), receiving commercial diet: ALA Group (ALAG) and Diabetic ALA Group (DALAG), fed diets with added ALA (300 mg/Kg bw). The diabetic groups received a single injection of streptozotocin (60 mg/kg). After sixty days of the diet, the animals were euthanized, and semen, testis and epididymis samples were collected. A histomorphometric analysis was performed to determine the epithelial height, tubular and luminal diameter, tubular and luminal area of seminiferous tubules and each epididymal region. Sertoli cells were evidenced using the antivimentin antibody and were quantified. The results were statistically analyzed by the ANOVA test. RESULTS: At the end of the experiment, the DALAG glycemia was signifi cantly lower than DCG. The histomorphometric parameters of the seminiferous and epididymal tubules did not show improvement in the DALAG. However, there was an improvement in the DALAG in terms of the concentration, motility and percentage of spermatic pathologies, as well as in the number of Sertoli cells (p<0.001). CONCLUSIONS: The results demonstrated that supplementation with the ALA antioxidant retards testicular lesions and preserve the process of spermatogenesis in diabetes.

Bentonites Modified with Phosphomolybdic Heteropolyacid (HPMo) for Biowaste to Biofuel Production.

Two bentonites from Paraíba (Northeastern Brazil) were impregnated with heteropoly phosphomolybdic H3PMo12O40 (HPMo). The materials produced were characterized by various techniques such as N2 adsorption-desorption (specific surface area, SSA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA/DTG), Scanning Electron Microscopy (SEM) equipped with Dispersive Energy X-ray spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-vis), acid-base titration analysis. The catalytic activity of these materials was tested in the esterification of a waste from palm oil deodorization and the main results obtained (about 93.3% of conversion) indicated that these materials have potential to act as heterogeneous solid acid catalysts. The prepared materials exhibited satisfactory catalytic performance even after a very simple recycling process in three reuse cycles, without significant loss of their activities.

Dermatological manifestations in patients with human T-cell lymphotropic virus at a reference service in Amazon.

INTRODUCTION: Individuals infected with the human T-cell lymphotropic virus type 1 (HTLV-1) commonly present skin lesions, which may be a warning sign for the diagnosis of infection. This study describes the most prevalent skin manifestations in HTLV carriers attended at the clinic of Núcleo de Medicina Tropical (NMT) of the Universidade Federal do Pará (UFPA) in Belém, Pará, Brazil. METHODS: This is a study of a series of cases of patients infected with human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) treated at NMT UFPA between 1999 and 2016. A descriptive analysis of data was applied. RESULTS: Among 788 surveyed medical records in the service, 15.10% (n = 119) were referred to the dermatology clinic. From the series of cases that presented with skin lesions, 66.39% were female and 33.61% were male, and the average age of this group was 48 years. There was a predominance of patients with noninfectious inflammatory manifestations (64.2%), followed by infectious ones (24.6%), and 1.58% with lymphoproliferative diseases. As for the group of lesions, 45.26% of the erythematous-squamous type were observed, followed by dyschromia (24.21%), and eczematous (14.74%). One patient with a diagnosis of adult T-cell leukemia/lymphoma, another with parapsoriasis, and four with infective dermatitis are highlighted. CONCLUSION: Skin disorders in the HLTV positive patient are important causes of referral to the dermatologist with etiological and skin lesions groups diversity. In the series of cases studied, lymphoproliferatives diseases and infective dermatitis associated with HTLV-1 were presented as a challenge for the diagnosis and clinical management of these patients.

Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients.

BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2-5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the region that codifies these proteins may influence both the infectivity and the replication of the virus. The gp46 gene has functional domains which have been associated with the inhibition of the formation of the syncytium, cell-cell transmission, and the production of antibodies. The present study investigated the genetic stability of the gp46 gene of HTLV-1 in an endemic region of Brazilian Amazonia. METHODS: Index case (IC - a sample of a given family group) carriers of HTLV-1 were investigated in the metropolitan region of Belém (Pará, Brazil) between January 2010 (registered retrospectively) and December 2015. The sequences that codify the gp46 were amplified by PCR, purified and sequenced (MF084788-MF084825). The gene was characterized using bioinformatics and Bayesian Inference. RESULTS: The 40 patients analyzed had a mean age of 45.2 years and 70% presented some type of symptom, with a predominance of pain and sensitivity, dysautonomia, and motor disorders. All patients presented the aA (Transcontinental Cosmopolitan) genotype, with an extremely low mutation rate, which is characteristic of the codifying region (aA - 1.83 × 10-4 mutations per site per year). The gp46 gene had a nucleotide diversity of between 0.00% and 2.0%. Amino acid mutations were present in 66.6% of the samples of individuals with signs/symptoms or diseases associated with HTLV-1 (p = 0.0091). Of the three most frequent mutations, the previously undescribed N93D mutant was invariably associated with symptomatic cases. CONCLUSIONS: The aA HTLV-1 subtype is predominant in the metropolitan region of Belém and presented a high degree of genetic stability in the codifying region. The rare N93D amino acid mutation may be associated with the clinical manifestations of this viral infection. IMPORTANCE: Little is known of the phylogeny of HTLV-1 in the endemic region of Brazilian Amazonia, and few complete gene sequences are available for the gp46 glycoprotein from the local population. The nucleotide sequences of the viral gp46 gene recorded in the present study confirmed the genetic stability of the region, and pointed to a homogeneous viral group, with local geographic characteristics. Further research will be necessary to more fully understand the molecular diversity of this protein, given the potential of this codifying region as a model for an effective HTLV-1 vaccine. The identification of a rare mutation (N93D), present only in symptomatic patients, should also be investigated further as a potential clinical marker. TRIAL REGISTRATION: ISRCTN 12345678, registered 28 September 2014.