Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.

In human metabolism, pyruvate dehydrogenase complex (PDC) is one of the most intricate and large multimeric protein systems representing a central hub for cellular homeostasis. The worldwide used antiepileptic drug valproic acid (VPA) may potentially induce teratogenicity or a mild to severe hepatic toxicity, where the underlying mechanisms are not completely understood. This work aims to clarify the mechanisms that intersect VPA-related iatrogenic effects to PDC-associated dihydrolipoamide dehydrogenase (DLD; E3) activity. DLD is also a key enzyme of α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, α-ketoadipate dehydrogenase, and the glycine decarboxylase complexes. The molecular effects of VPA will be reviewed underlining the data that sustain a potential interaction with DLD. The drug-associated effects on lipoic acid-related complexes activity may induce alterations on the flux of metabolites through tricarboxylic acid cycle, branched-chain amino acid oxidation, glycine metabolism and other cellular acetyl-CoA-connected reactions. The biotransformation of VPA involves its complete ß-oxidation in mitochondria causing an imbalance on energy homeostasis. The drug consequences as histone deacetylase inhibitor and thus gene expression modulator have also been recognized. The mitochondrial localization of PDC is unequivocal, but its presence and function in the nucleus were also demonstrated, generating acetyl-CoA, crucial for histone acetylation. Bridging metabolism and epigenetics, this review gathers the evidence of VPA-induced interference with DLD or PDC functions, mainly in animal and cellular models, and highlights the uncharted in human. The consequences of this interaction may have significant impact either in mitochondrial or in nuclear acetyl-CoA-dependent processes.

Study of the Effect of Hyperbaric Oxygen Therapy on the Viability of Dorsal Cutaneous Flaps in Tobacco-Exposed Rats.

BACKGROUND: Smoking causes a threefold increase in the risk of surgical complications in flaps. Hyperbaric oxygen therapy (HBOT) increases the viability of chronic wounds. However, there are few studies concerning the effects of HBOT on surgical flaps in patients who smoke. This study aimed to analyze the effect of HBOT on the viability of cutaneous flaps in tobacco-exposed rats. METHODS: Twenty Wistar rats were exposed to tobacco smoke for two months. Following this period, all animals underwent a dorsal cutaneous flap (3 × 10 cm) surgery and were divided into two groups: control (n = 10) and HBOT (n = 10). HBOT was performed in seven daily sessions (2 ATA, 90 min). After seven days, the animals were euthanized. The outcomes were total area, viable area, viable area/total area rate, analysis of dermal appendages and angiogenesis (hematoxylin-eosin), and gene expression analysis of iNOS and VEGF-a biomarkers. RESULTS: The HBOT group showed an increase in viable area compared with the control group (84% versus 47%, p = 0.009, respectively). The HBOT group also showed an increase in appendage units (1.69 ± 0.54 versus 1.87 ± 0.58, p = 0.04) and angiogenesis density (1.29 ± 0.45 versus 1.82 ± 0.64, p < 0.001) compared to the control group. There was a difference between the control and HBOT groups in iNOS levels (0.926 ± 1.4 versus 0.04 ± 0.1 p = 0.002, respectively). However, this study did not show a difference between the groups concerning the gene expression of VEGF-a. CONCLUSION: The use of hyperbaric oxygen therapy increased the viability of cutaneous flaps in tobacco-exposed rats and decreased iNOS mRNA levels; however, it did not change VEGF-a levels. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Fcγ-RI, Fcγ-RII and IL-10 as predictive biomarkers for post-therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime® , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-ß modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-ß and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

Song recorded near a super-group of humpback whales on a mid-latitude feeding ground off South Africa.

Humpback whales (Megaptera novaeangliae) are well known for their complex song which is culturally transmitted and produced by males. However, the function of singing behavior remains poorly understood. Song was observed from 57 min of acoustic recording in the presence of feeding humpback whales aggregated in the near-shore waters on the west coast of South Africa. The structural organization of the song components, lack of overlap between song units, and consistency in relative received level suggest the song was produced by one "singer." The unusual timing and location of song production adds further evidence of plasticity in song production.

Advances in methods for characterization of hepatic urea cycle enzymatic activity in HepaRG cells using UPLC-MS/MS.

Current methodologies for the assessment of urea cycle (UC) enzymatic activity are insufficient to accurately evaluate this pathway in biological specimens where lower UC is expected. Liver cell lines, including HepaRG, have been described to have limited nitrogen fixation through the UC, limiting their applicability as biocomponents for Bioartificial Livers (BAL). This work aims to develop novel and sensitive analytical solutions using Mass Spectrometry-based methodology to measure the activity of four UC enzymes in human liver and HepaRG cells. Activity of carbamoyl-phosphate synthetase I (CPS I), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL) and arginase (ARG I and II) was determined on homogenates from normal human liver and HepaRG cells cultured in monolayer or in the AMC-BAL. Enzyme products were determined by stable-isotope dilution UPLC-MS/MS. Activity of CPS I, OTC and ARG I/II enzymes in HepaRG monolayer cultures was considerably lower than in human control livers albeit an increase was achieved in HepaRG-BAL cultures. Improved analytical assays developed for the study of UC enzyme activity, contributed to gain understanding of UC function in the HepaRG cell line. The decreased activity of CPS I suggests that it may be a potential rate-limiting factor underlying the low UC activity in this cell line.

Prevalence and Severity of Ratoon Stunt in Commercial Brazilian Sugarcane Fields.

Brazil has 9 million ha of sugarcane, 85% of which are located in the Center-South area of the country. Field trials and surveys around the globe have shown that ratoon stunt disease (RSD), caused by Leifsonia xyli subsp. xyli, can severely reduce tonnage yield. Previous small-scale studies in Brazil have demonstrated RSD infection in all varieties, with values varying from 25 to 68%. Nevertheless, the prevalence and severity of RSD in commercial fields had not previously been assessed. To address this issue, we surveyed 13,173 ha in 1,154 fields of the eight main sugarcane varieties of the Center-South area, taking 92,114 samples from 50 mills in five different states. Our data showed that 10% of fields were infected, and that 58% of mills had at least one RSD-infected field. The variety RB92579 had the highest proportion of infected fields (17%) and, on average, the prevalence and severity in these fields was high compared with other varieties. RB867515, the most cultivated in Brazil, showed infection in 6.2% of sampled fields (5.5% of sampled area) causing an estimated annual economic loss of over US$1 million. This was the first time the economic importance of RSD on Brazilian commercial sugarcane production was estimated. The Cerrado region had the highest prevalence of RSD: 16% of fields, 17% of the cultivated area, and 82% of mills. The use of diseased planting material was identified in 9% of plant cane fields, representing 10% of the cultivated area. Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Diversity and genetic parameter estimates for yield and its components in Jatropha curcas L.

Jatropha curcas L. is one of the most promising oilseeds for biodiesel and biokerosene production, but few basic studies or breeding programs have been conducted for the species. We estimated genetic parameters and diversity based on 10 yield traits in 77 half-sib progenies of J. curcas after 52 months in the field, and evaluated correlations between them and the oil content of the seeds. The mean grain yield per plant was 377.9 g (ranging from 169.8 to 772.1 g) and the mean oil content was 36.2% (ranging from 30 to 39.6%). Moderate estimates of heritability at the mean progeny level were obtained for the length of the fruit (84.7%), length (69.1%) and width (68.2%) of the seed, and grain yield per plant (62.2%). Oil content was only positively and significantly correlated with 100-seed weight. Our study revealed a range of possible crosses to be investigated in J. curcas. Progeny production should be evaluated over several crop seasons for the accurate selection of the best progenies.

Protective Profile Involving CD23/IgE-mediated NO Release is a Hallmark of Cutaneous Leishmaniasis Patients from the Xakriabá Indigenous Community in Minas Gerais, Brazil.

In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriabá indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-γ/IL-4 cytokines environment, was evaluated in localized cutaneous leishmaniasis (LCL) carriers and positive Montenegro skin test (MST) individuals without skin lesion (MT(+) SL(-)). Our data demonstrated that the higher frequency of CD23(+) CD14(+) monocytes and the increased serum levels of IgE observed in the LCL group were even higher in LCL carriers with late lesions (LCL≥60). Furthermore, patients with LCL presented increased NO production after Leishmania (Viannia) braziliensis stimulation and this NO profile was independent of the time of the lesion (recent LCL<60 or late LCL≥60). We also showed that the increased frequency of IFN-γ(+) and IL-4(+) CD4(+) T cells is related to the MT(+) SL(-) group. The results of biomarker signature curves demonstrated that in the MT(+) SL(-) group, the index signature was characterized by DAF-2T(+) CD14(+)/IL-4(+) CD8(+)/IFN-γ(+) CD4(+)/IL-4(+) CD4(+). On the other hand, the LCL group presented a higher index of DAF-2T(+) CD14(+)/CD23(+) CD14(+)/IL-4(+) CD8(+), associated with a lower index of IFN-γ(+) CD8(+). Considering the time of lesion, data analysis demonstrated that the main differences observed were highlighted in LCL<60 patients, with a higher index of CD23(+) CD14(+), which was also present in LCL≥60 patients. In conclusion, our data suggest that the protective immune response involving CD23-IgE-mediated NO release is a hallmark of patients with LCL. However, in MT(+) SL(-) individuals, another different leishmanicidal mechanism seems to be involved.

Oestrous cycle-dependent expression of Fas and Bcl2 family gene products in normal canine endometrium.

During the oestrous cycle canine endometrium undergoes cyclical cellular proliferation, apoptosis and differentiation. To study the regulation of endometrial apoptosis and proliferation events the expression of apoptosis-related genes was analysed by real-time polymerase chain reaction and cellular expression of their proteins was identified through immunohistochemistry. Cellular apoptosis and proliferation events were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and proliferation marker Ki67 immunostaining, respectively. The highest proliferative index was observed in the follicular phase (all endometrial cellular components) and at early dioestrus (basal glands). This was associated with a low apoptotic index and a strong expression of anti- (Bcl2) and pro-apoptotic proteins (Fas, FasL, Bax). Subsequently (Days 11-45 of dioestrus), basal glandular epithelium experienced the highest apoptotic index, coincidental with a decrease of Bcl2 expression and a low ratio of Bcl2/Bax transcription. An increase in the apoptotic index of crypts, stromal and endothelial cells was observed at late dioestrus and the beginning of anoestrus. These results indicate that pro- and anti-apoptotic proteins regulate the balance between cell proliferation and death in the canine endometrium during the oestrous cycle. High Bcl2 expression in both the follicular and early dioestrous phases stimulate glandular proliferation and prevent apoptosis but, in the non-pregnant uterus, a decrease in Bcl2 expression together with an increase in pro-apoptotic proteins induces apoptosis of basal glandular epithelium cells.

In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid ß-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions-c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)-were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.

Comparative study of putative 9-cis-epoxycarotenoid dioxygenase and abscisic acid accumulation in the responses of Sunki mandarin and Rangpur lime to water deficit.

Abscisic acid is a plant hormone that participates in essential plant physiological processes, especially during adaptation to many environmental stresses, such as water deficit. The relationship between ABA accumulation and the expression of putative carotenoid cleavage dioxygenase (CCD) genes was investigated in the pot-cultivated leaves and roots of the 'Rangpur' lime and 'Sunki Maravilha' mandarin plants. Transpiration, stomatal resistance and leaf growth were evaluated when these genotypes were subjected to continuous water deficit. Under water deficit conditions, the 'Rangpur' lime extracts used greater amounts of water when compared to the 'Sunki Maravilha' plants, which reached the greatest stomatal resistance 5 days before 'Rangpur' lime. When subjected to water deficit, the roots and leaves of 'Sunki Maravilha' showed a progressive increase in ABA accumulation; however, in 'Rangpur' lime, alternations between high and low ABA concentrations were observed. These results suggest a retroactive feeding regulation by ABA. In 'Rangpur' lime the NCED2, NCED3 and CCD4a genes were expressed at the highest levels in the roots, and NCED5 was highly expressed in the leaves; in 'Sunki Maravilha', the NCED2 and NCED5 genes were most highly expressed in the roots, and NCED2 was most highly expressed in the leaves. However, for both genotypes, the transcription of these genes only correlated with ABA accumulation during the most severe water deficit conditions. The 'Rangpur' lime behaved as a vigorous rootstock; the leaf growth remained unaltered even when water was scarce. However, 'Sunki Maravilha' adaptation was based on the equilibrium of the response between the root and the aerial tissues due to water restriction. The use of the Sunki mandarin in combination with a scion with similar characteristics as its own, which responds to water deficit stress by accumulating ABA in the leaves, may display good drought tolerance under field conditions.

Protein restriction does not impair adaptations induced in cardiomyocytes by exercise in rats.

The effect of a treadmill running program on physical performance and morphofunctional adaptations was investigated in control and malnourished rats. Male 4-week old Wistar rats were randomized in groups of 12 animals: control trained (CT), control sedentary (CS), malnourished trained (MT) and malnourished sedentary (MS). Control and malnourished animals received chow with 12% protein or 6% protein, respectively. Trained groups were subjected to a treadmill running program for 8 weeks. Physical performance, biochemical parameters, cardiomyocytes morphology and biomechanics were determined. Malnourished animals presented reduction in body mass, serum levels of total protein, albumin and hemoglobin compared to the control groups. At 1 and 3 Hz cardiomyocytes from CT and MT showed higher cell shortening, speed of contraction and relaxation compared to the other groups. At 3 Hz cardiomyocytes from MS showed reduction in cell shortening and speed of contraction compared to CS. Protein restriction does not prevent the improvement in physical performance or cardiomyocytes biomechanical efficiency and growth in response to exercise. These findings could represent a modulatory effect of exercise to maintain cardiomyocyte growth at the expense of reducing the rate of body growth in order to ensure proper cellular function in conditions of cardiovascular overload imposed by exercise.

Pyruvic acid as attenuator of water deficit in cotton plants varying the phenological stage.

The lack of water during crop growth causes damage to any production system, especially when it occurs during the initial establishment or beginning of the reproductive stage. Although cotton can be properly managed in regions with water limitation, its yield is affected at different levels according to the genetics of the cultivar adopted. Exogenous application of some organic components has shown a stress-mitigating effect and can be a valuable procedure to enhance the yield of water stress-sensitive cultivars. The objective of this work was to evaluate the benefits of exogenous application of pyruvic acid (100 µM) in cotton plants under water deficit varying the phenological stage of the crop. The experiment was conducted in a greenhouse, where the plants were grown in pots and subjected to seven days of water suspension, initiated individually in stages V2 and B1. Each pot contained two plants. The treatments adopted were: T1 - control, T2 - water suppression; and T3 - water suppression + pyruvate application. The design was randomized blocks in a factorial scheme (3 × 3) with three replicates. The reductions in gas exchange and growth of the cultivars BRS Seridó, CNPA 7MH and FM 966 were more significant in the reproductive stage, especially for FM 966, which was more sensitive. Pyruvate application reduced the effects of water suppression on boll production by 31% in BRS Seridó and 34% in CNPA 7MH and FM 966.

Calcium pyruvate in the attenuation of the water deficit on the agro-industrial quality of ratoon sugarcane.

Sugarcane is one of the largest agricultural commodities when considering the export volume and the number of jobs generated. Sugarcane production in the Brazilian Northeast region is generally low due to several factors, including the irregular rainfall distribution, which highlights the importance of studies aimed at mitigating the deleterious effects of water stress. In this scenario, this study aimed to evaluate calcium pyruvate as a water deficit attenuator on the agro-industrial quality of sugarcane in the second cycle of cultivation. The experiment was conducted out under greenhouse conditions of the Federal University of Campina Grande, where five sugarcane commercial genotypes tested (G1- RB863129, G2- RB92579, G3- RB962962, G4- RB021754, and G5- RB041443) and three irrigation management strategies (E1- full irrigation, E2- water deficit with application of 30 mM of calcium pyruvate, and E3- water deficit without calcium pyruvate application), distributed in randomized blocks in 5 × 3 factorial arrangement with three replications. The RB021754 genotype under water deficit and without foliar application of calcium pyruvate increased the fiber content (13.2%) and the sugarcane moist cake weight (143.5 g). The effects of water deficit in sugarcane genotypes are attenuated by the exogenous application of 30 mM of calcium pyruvate, with benefits on the polarized sucrose content, apparent sucrose content of the juice, soluble solids content, purity, corrected cane POL, total recoverable sugars, and stem mass in relation to plants under water deficit without calcium pyruvate application.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients.

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients.

Frequency of human papillomavirus types 16, 18, 31, and 33 and sites of cervical lesions in gynecological patients from Recife, Brazil.

Human papilloma virus (HPV) is a well-established cause of cervical cancer. While many studies have been performed so far on HPV viral biology, mode of infection and prevention measures, scanty information is available on lesion sites of infected women and the incidence of viral types at specific locations. We looked for a possible relationship between the most common viral types (HPVs 16, 18, 31, 33) found in Recife, PE, Brazil, and lesion sites. We examined 396 HPV-positive women at the Gynecological Unit of the IMIP at Recife; 288 women were positive for HPV 16, 18, 31, or 33, present as a single-virus type or as co-infection. HPV 16 was the most frequent virus type found in the vulva, vagina, uterine cervix-vagina, and uterine cervix. HPV 31 was the second prevalent virus type in vulva, vagina, uterine cervix-vagina, uterine cervix, and mole. HPVs 18 and 33 were present with similar frequencies in the mole-vulva region. Among the co-infections, HPV 16/18 and HPV16/31 were the most frequent in our study group, followed by HPV 16/33.

Analysis of a Fast Control Allocation approach for nonlinear over-actuated systems.

Autonomous Robots with multiple directional thrusters are normally over-actuated systems that require nonlinear control allocation methods to map the forces that drive the robot's dynamics and act as virtual control variables to the actuators. This process demands computational efforts that, sometimes, are not available in small robotic platforms. The present paper introduces a new control allocation approach with fast convergence, high accuracy, and dealing with complex nonlinear problems, especially in embedded systems. The adopted approach divides the desired nonlinear system into coupled linear problems. For that purpose, the Real Actions (RAs) and Virtual Control Variables (VCVs) are broke in two or more sets each. While the RA subsets are designed to linearize the system according to different input subspaces, the VCV is designed to be partially coupled to overlap the output subspaces. This approach generates smaller linear systems with fast and robust convergence used sequentially to solve nonlinear allocation problems. This methodology is assessed in mathematical tutorial cases and over-actuated UAV simulations.

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review.

Vocal fold leukoplakia (VFL) has a risk of malignant transformation. Therefore, patients can have symptoms such as dysphonia, vocal strain, difficulty breathing, and dysphagia. Additionally, there is a genetic predisposition that can be associated with genetic polymorphisms. We aimed to evaluate the influence of genetic polymorphisms and protein levels in the etiology of VFL. Our study followed the PRISMA checklist and was registered on PROSPERO database. The questions were: "Are genetic polymorphisms involved in the etiology of VFL? Are protein levels altered in patients with VFL?". Eligibility criteria were case control studies that compared the presence of polymorphisms or/and protein levels of subjects diagnosed with VFL and healthy controls. Of the 905 articles retrieved, five articles with a total of 1038 participants were included in this study. The C allele of the single nucleotide polymorphisms (SNP)-819 T/C IL-10, A allele of the SNP -592 A/C IL-10, CT genotype of the SNP rs11886868 C/T BCL11A, GG genotype of the SNP rs4671393 A/G BCL11A, LL genotype, and L allele of (GT)n repeat polymorphisms of the HO-1 were risk factors for VFL development. Nevertheless, there was a lack of association between VFL and the -1082 A/G IL-10, rs14024 CK-1, and -309 T/G Mdm2 SNPs. The concentrations of the MDM2, BCL11A, and HO-1 proteins were modified, while IL-10 levels were normally expressed in these subjects. In conclusion, most markers evaluated in this review could be potential indicators to develop effective therapies, avoiding a malignant transformation of the lesion.