Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

miRNA-205-5p can be related to T2-polarity in Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: microRNAs (miRNAs) are directly associated with inflammatory response, but their direct role in CRSwNP (chronic rhinosinusitis with nasal polyps) remains evasive. This study aimed to compare the expression of several miRNAs in tissue samples obtained from patients with CRSwNP and controls and to evaluate if miRNAs correlate to a specific inflammatory pattern (T1, T2, T17, and Treg) or intensity of symptoms in CRSwNP. METHODS: nasal polyps (from patients with CRSwNP - n=36) and middle turbinate mucosa (from control patients - n=41) were collected. Microarray determined human mature miRNA expression, and the results obtained were validated by qPCR. miRNAs that were differentially expressed were then correlated to cytokine proteins (by Luminex), tissue eosinophilia, and SNOT-22. RESULTS: After microarray and qPCR analyses, six microRNAs were up-regulated in CRSwNP samples when compared with controls: miR-205-5p, miR-221-3p, miR-222-3p, miR-378a-3p, miR-449a and miR-449b-5p. All these miRNAs are directly implicated with cell cycle regulation and apoptosis, and to a minor extent, with inflammation. Importantly, miR-205-5p showed a significantly positive correlation with IL-5 concentration and eosinophil count at the tissue and with the worst SNOT-22 score. CONCLUSIONS: miRNA 205-5p was increased in CRSwNP compared to controls, and it was especially expressed in CRSwNP patients with higher T2 inflammation (measured by both IL-5 levels and local eosinophilia) and worst clinical presentation. This miRNA may be an interesting target to be explored in patients with CRSwNP.

Dual-task gait speed assessments with an electronic walkway and a stopwatch in older adults. A reliability study.

BACKGROUND/OBJECTIVES: Slow gait speed prospectively predicts elevated risk of adverse events such as falls, morbidity, and mortality. Additionally, gait speed under a cognitively demanding challenge (dual-task gait) predicts further cognitive decline and dementia incidence. This evidence has been mostly collected using electronic walkways; however, not all clinical set ups have an electronic walkway and comparability with simple manual dual-gait speed testing, like a stopwatch, has not yet been examined. Our main objective was to assess concurrent-validity and reliability of gait speed assessments during dual-tasking using a stopwatch and electronic walkway in older adults with mild and subjective cognitive impairment (MCI and SCI). DESIGN: Cross-sectional, reliability study. SETTING: Clinic based laboratory at an academic hospital in London, ON, Canada. PARTICIPANTS: 237 walk tests from 34 community-dwelling participants (mean age 71.84 SD 5.38; 21 female - 62%, 13 male - 38%) with SCI and MCI. were included from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. INTERVENTION: Each participant performed seven walk tests: three single gait walks at their normal pace, three dual-task walks (walking and counting backwards by one, by sevens, and naming animals), and one fast walk. MEASUREMENTS: Gait speed (cm/s) for each walk was measured simultaneously with an electronic walkway (Zeno Mat®) and a handheld stopwatch (Ultrak chronometer®). Dual-task cost (DTC) was calculated for the three individual dual-task walks as [((single gait speed - dual-task gait speed) / single gait speed) ∗ 100]. Level of agreement between the two measurement methods was analyzed using Pearson correlations, paired t-tests, and Bland-Altman plots. RESULTS: Gait speed was consistently lower when measured with the stopwatch than with the electronic walkway (mean speed difference: 10.6 cm/s ± 5.1, p < 0.001). Calculating DTC, however, yielded very similar results with both methods (mean DTC difference: 0.19 ± 1.18, p = 0.872). The higher the DTC, the closer the measurement between methods. CONCLUSION: Assessing and calculating DTC with a stopwatch is simple, accessible and reliable. Its validity and reliability were high in this clinical sample of community older adults with SCI and MCI.

Synthesis, characterization and applications of maghemite beads functionalized with rabbit antibodies.

Magnetic nanoparticles (NPs) have attracted great attention owing to their applications in the biomedical field. In the present work, maghemite (γFe2O3) NPs of 6.5 nm were prepared using a sonochemical method and used to prepare magnetic beads through silanization with 3-aminopropyltrimethoxysilane (APTS). Subsequently, amino groups in the resulting APTS-γFe2O3 beads were converted to carboxylic acid (CARB-γFe2O3) through the succinic anhydride reaction, as confirmed by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy and dynamic light scattering (DLS) measurements. The size of these beads was measured as 12 nm and their hydrodynamic diameter as 490 nm, using TEM analysis and DLS, respectively. The CARB-γFe2O3 beads were further functionalized by immobilizing rabbit antibodies on their surfaces; the immobilization was confirmed by flow cytometry and ionic strength. The samples were further characterized by Mössbauer spectroscopy and DC magnetization measurements. Studies on magnetic relaxivities showed that magnetic beads present great potential for application in MR imaging.

Surgical sponge associated with platelets rich plasma in skin mesh grafts and layer in rabbits (Oryctolagus cuniculus) / Esponja cirúrgica associada com plasma rico em plaquetas em enxertos cutâneos em malha e camada em coelhos (Oryctolagus cuniculus)

The aim of this study was to evaluate of the efficacy of PRP employment associated with surgical sponges to improve the integration of the graft in the recipient bed. It was held at the Veterinary Hospital UNESP, Campus of Jaboticabal - SP, a study of 64 rabbits, divided into eight groups with eight animals. The groups were divided in control with saline solution 0,9%, control with PRP both without the sponge, surgical sponge with PRP, surgical sponge without PRP, and were used mesh and layer grafts in the respective groups. The data were submitted to statistical analysis (paired t-test, Kruskal-Wallis test, with subsequent use of the multiple comparison tests of Dunn, analysis of variance (F) test, Tukey test, P< 0.05). Edema and exudate with 3 and 3 and 7 days (P= 0,03 e P= 0,0049); coloring on the 14th day (P= 0,0001); cosmetic appearance on the 7th and 14th day (P= 0,0026 and P= 0,0001); mononuclear cells (P= 0,01) and polymorphonuclear (P= 0,01); fibroblast proliferation (P= 0,01); collagenous (P= 0,05); hemorrhage (P-007); necrosis and re-epithelialization (P= 0,2928 and P= 0,1). We concluded that the use of Platelet Rich Plasma Gel on skin grafts associated with a sponge as a compressive dressing promote the skin graft survival without a previous granulation tissue.(AU)

O objetivo deste estudo foi avaliar a eficácia do PRP associado com esponjas cirúrgicas na integração do enxerto ao leito receptor. Realizou-se, no Hospital Veterinário da Unesp, Jaboticabal, SP, um estudo com 64 coelhos, separados em oito grupos, com oito animais. Os grupos foram: Gprpc (PRP, sem esponja cirúrgica, enxerto camada), Gprpce (PRP, esponja cirúrgica, enxerto camada), Gcc (solução fisiológica 0,9%, sem esponja cirúrgica, enxerto camada), Gcce (solução fisiológica 0,9%, esponjas cirúrgicas, enxerto camada), Gprpm (PRP, sem esponja cirúrgica, enxerto malha), Gprpme (PRP, esponja cirúrgica, enxerto malha), Gcm (solução fisiológica 0,9%, sem esponja cirúrgica, enxerto malha) e Gcce (solução fisiológica 0,9%, esponjas cirúrgicas, malha). Os dados foram analisados pelo teste t emparelhado, Kruskal-Wallis, análise de variância, e teste de Tukey (P<0,05). Edema e exsudato presente com três e sete dias (P=0,03 e P=0,0049); coloração cianótica no 14º dia (P=0,0001); aspecto cosmético bom no sétimo e no 14º dia (P=0,00026 e P=0,0001); presença de células mononucleares (P=0,01) e polimorfonucleares (P=0,01); proliferação de fibroblastos discreta (P=0,01); colagenização intensa (P=0,05); hemorragia discreta (P=0,007); ausência de diferença significativa em necrose e reepitelização (P=0,2928 e P=0,1). Conclui-se que o emprego do PRP gel em enxertos cutâneos associando esponjas cirúrgicas como curativo compressivo favorece sua integração ao leito receptor sem a presença prévia de tecido de granulação.(AU)

Expression of iron-related proteins in feline and canine mammary gland reveals unexpected accumulation of iron.

Dysregulation of cellular iron homeostasis in human breast cancer is reflected by the altered expression of regulatory proteins. The expressions of iron-related proteins in the mammary glands of cats and dogs have not been assessed. We evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron deposition was detected using Perls' Prussian blue staining. We found no major differences in the expression of iron-related proteins between benign and malignant mammary gland lesions in either cats or dogs; however, these species exhibited accumulation of iron in benign lesions. Our findings provide an explanation for the absence of higher iron requirements by tumor cells in these animals. Further investigation of local iron homeostasis in cats and dogs and differences in their physiology compared to human breast cancer is required.

Efficacy of oral diclofenac with or without codeine for pain control after invasive bilateral third molar extractions.

Postoperative pain and inflammation after oral surgery is mostly managed using non-steroidal anti-inflammatory drugs (NSAIDs). However, opioids combined with NSAIDs may improve pain management in patients, especially after traumatic oral surgery. Few studies have compared NSAIDs with and without opioid use after oral and maxillofacial surgery. This randomized, double-blind, cross-over study compared the clinical efficacy of either diclofenac (50mg) and codeine (50mg) or diclofenac alone (50mg) for the management of postoperative pain after invasive third molar surgery. Volunteers (n=46) who were scheduled to undergo the removal of symmetrically positioned lower third molars in two separate appointments were included. They reported significantly less postoperative pain at various time points within 24h after surgery and also consumed significantly less rescue medication (paracetamol (acetaminophen)) throughout the study when they took diclofenac combined with codeine than when they took only diclofenac. In conclusion, oral diclofenac with codeine was more effective for managing postoperative pain than diclofenac without codeine. It was expected that patients taking two pain medications after surgery would generally have less pain than when taking only one of the two medications. The prospective cross-over design of the present work makes this study distinct from many others.

Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study.

BACKGROUND: Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. MATERIAL AND METHODS: Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. RESULTS: Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. CONCLUSIONS: In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE.

Differential effects of palmitoleic acid on human lymphocyte proliferation and function.

BACKGROUND: Palmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA). METHODS: Human lymphocytes were isolated from peripheral blood of health men and cultured in the presence of growing concentrations of PA or OA (5 to 200 µM), for 24 h. After that, cells were collected and cytotoxicity evaluated by flow cytometry. Then, we analyzed proliferative capacity in lymphocytes treated with non toxic concentrations of PA and OA (25 and 50 µM, respectively), in the presence or absence of concanavalin A (ConA). The Th1/Th2/Th17 cytokine production was determined by the Cytometric Bead Array. CD28 and CD95 surface expression and T regulatory cell percentage were determined by flow cytometry. RESULTS: We observed that PA is toxic to lymphocytes above 50 µM. PA promoted a decrease of lymphocyte proliferation stimulated by ConA in both concentrations. PA also decreased CD28 externalization and increased CD95. On the other hand, OA did not alter these parameters. In the same way, PA reduced IL6, IFN-gamma, TNF-alpha and IL17A production in both concentration and IL2 only at 50 µM (in the presence of ConA). OA promoted IFN-gamma reduction in both concentrations and an increase of IL-2, IL4 and IL10 at 25 µM. Both fatty acids decreased the percentage of T regulatory cells. CONCLUSION: In conclusion, PA promoted a suppressive effect on lymphocyte proliferation characterized by a decrease of Th1 and Th17 response, and co-stimulatory molecule (CD28). However, OA increased lymphocyte proliferation through IL2 production and Th2 response. These results also show a more suppressive effect of PA on lymphocytes in comparison to OA.

Precocidade sexual, eficiência reprodutiva e desempenho produtivo de matrizes jovens Nelore e cruzadas / Sexual precocity, reproductive efficiency and productive performance of Nelore and crossbred young cows

Com o objetivo de avaliar matrizes da raça Nelore (NE) e cruzadas 1/2 Angus + 1/2 Nelore (AN), 1/2 Caracu + 1/2 Nelore (CN) e 1/2 Senepol + 1/2 Caracu (SC) quanto à precocidade sexual em sistemas de recria a pasto, eficiência reprodutiva e desempenho produtivo das matrizes em cada grupo genético (GG), matrizes desses grupos foram produzidas por três safras. Foram avaliadas 40 matrizes AN, 37 CN, 51 NE e 43 SC. Para prenhez precoce, matrizes AN apresentaram taxa de prenhez de 92,2% contra 29,1% para CN, 22,6% para SC e 1,1% para NE. Na prenhez convencional, matrizes AN obtiveram 99,4%, 98,8% para CN, 84,4% para SC e 80,0% para NE. A reconcepção das matrizes AN foi 86,3%, 75,1% de CN, 49,6% de NE e 43,6% de SC. Matrizes AN tiveram menor média de idade ao primeiro parto em meses, 26,36±0,79, contra 31,33±0,86 para CN, 33,51±0,98 para SC e 38,08±0,74 para NE. Para peso ao desmame, crias three-cross das AN pesaram mais que as F1 das NE, por volta de 19%. Para relação de peso ao desmame, não houve diferenças estatísticas entre GG. Matrizes AN foram superiores às demais nos aspectos reprodutivos e produtivos, seguidas das matrizes CN.(AU)

With the aim of evaluating Nelore (NE), 1/2 Angus + 1/2 Nelore (AN), 1/2 Caracu + 1/2 Nelore (CN), and 1/2 Senepol + 1/2 Caracu (SC) females for sexual precocity on pasture backgrounding, reproductive efficiency and productive performance of cows and their calves of each genetic group (GG), animals of these groups were produced for three years. A total of 40 AN, 37 CN, 51 NE and 43 SC cows were evaluated. For early heifer pregnancy, AN cows had pregnancy rate of 92.2% compared to 29.1% for CN, 22.6% for SC and 1.1% for NE. For conventional heifer pregnancy AN obtained 99.4%, CN with 98.8%, SC with 84.4% and NE with 80.0%. The first reconception of AN cows were 86.3%, 75.1% for CN, 49.6% for NE and 43.6% for SC. AN cows also had lower age at first calving in months, 26.36±0.79, compared to 31.33±0.86 for CN, 33.51±0.98 for SC and 38.08±0.74 for NE. For weaning weigth the three-cross from AN were heavier than the F1s from NE, by a margin of 19%. For calf:cow weight ratio there was no statistical difference among GG. AN cows were superior to the others in both productive and reproductive aspects, followed by the CN cows.(AU)

Biometria e parâmetros hematológicos em tartarugas da Amazônia de um criatório comercial de Rio Branco/AC / Biometric and haematological indices in turtles from the Amazon farm in Rio Branco/AC

Com o objetivo de definir os valores biométricos e quantificar parâmetros hematológicos como hematócrito, concentração de proteínas plasmáticas totais e leucócitos totais de tartarugas da espécie Podocnemis expansa, coletou-se um mililitro de sangue da veia femoral de 60 exemplares aparentemente saudáveis. Os animais obtidos do criatório particular, Estância Terra, localizado no estado do Acre, foram classificados em seis grupos de pesos diferentes. Durante a biometria, foram tomadas medidas de peso, comprimento e largura da carapaça e do plastrão, para as análises da correlação dos parâmetros de tamanho e massa corporal entre os indivíduos do mesmo grupo. Os valores observados indicaram que o grupo 06, que inclui os animais com massa acima de 26 kg, apresentou melhor correlação entre as massas individuais de cada animal (r = 0,97) Enquanto que, o grupo 02 (massa entre 21 e 25 kg) apresentou a pior correlação entre as massas (r = 0,34). O resultado da média total de hematócrito de todos os animais deste experimento foi de 10,56%. A concentração das proteínas plasmáticas totais foi de 3,69g dL-1, e a média de leucócitos totais foi de 51466,66µL. Estes parâmetros são considerados fora do padrão quando comparados com os valores encontrados em animais saudáveis da mesma espécie. Assim, este trabalho pode contribuir com informações sobre os dados biométricos e parâmetros hematológicos de P. expansa de cativeiro e demonstra a importância do monitoramento da sanidade dos animais em cativeiro, prevenindo manifestação de enfermidades que poderão pôr em risco a saúde de todo o plantel.(AU)

The aim of this study was defined the biometric values and quantify hematological parameters such as hematocrit, concentration of total plasma proteins and total leukocytes for Podocnemis expansa, we collect one milliliter of blood from the femoral vein of 60 specimens apparently healthy. The animals were collected from a private farm, Estancia Terra, located in Rio Branco in the state of Acre, and were classified into six groups of different weights. During the collection of biometric data, weight measurements were taken, and length and width of the carapace and plastron, for the analysis of correlation between the size parameters and body mass between individuals of the same group. The values observed indicate that the group 06, which includes animals with mass above 26kg, showed the best correlation between the individual masses of each animal (R = 0.97), while the group 02 (weight 21 to 25kg) showed the worst correlation between the mass (r = 0.34). The result of the overall average hematocrit of all animals of this experiment was 10.56%. The concentration of total plasma proteins was 3,69g DL-1 and the average total number of leukocytes was 51466,66µL. These parameters are considered abnormal when compared to the values found in healthy animals of the same species. This work contributes with information about biometric data and hematological parameters of P. expansa captivity and demonstrates the importance of monitoring health, preventing diseases that may endanger the health of all animals in the farm.(AU)

Toward an Automated Identification of Anastrepha Fruit Flies in the fraterculus group (Diptera, Tephritidae).

In this study, we assess image analysis techniques as automatic identifiers of three Anastrepha species of quarantine importance, Anastrepha fraterculus (Wiedemann), Anastrepha obliqua (Macquart), and Anastrepha sororcula Zucchi, based on wing and aculeus images. The right wing and aculeus of 100 individuals of each species were mounted on microscope slides, and images were captured with a stereomicroscope and light microscope. For wing image analysis, we used the color descriptor Local Color Histogram; for aculei, we used the contour descriptor Edge Orientation Autocorrelogram. A Support Vector Machine classifier was used in the final stage of wing and aculeus classification. Very accurate species identifications were obtained based on wing and aculeus images, with average accuracies of 94 and 95%, respectively. These results are comparable to previous identification results based on morphometric techniques and to the results achieved by experienced entomologists. Wing and aculeus images produced equally accurate classifications, greatly facilitating the identification of these species. The proposed technique is therefore a promising option for separating these three closely related species in the fraterculus group.

Insight into dopamine-dependent planning deficits in Parkinson's disease: A sharing of cognitive & sensory resources.

Cognitive and sensorimotor processes are both needed for successful planning of footsteps during complex gait situations, but the interaction between these factors during motor planning, as well as their response to dopaminergic treatment is poorly understood in Parkinson's disease (PD). In the current study, we evaluated walking and gaze behaviors of individuals with PD while planning an approach toward an obstacle to be stepped over. The obstacle clearance task was completed both ON and OFF dopaminergic medication by individuals with Parkinson's disease (n=20) and compared to healthy age-matched control participants (n=19), as well as with and without an auditory digit monitoring dual task. In this novel protocol of synchronized gaze and gait data collection, each trial was split into an early and late phase prior to the obstacle, providing a unique opportunity to examine dopamine-dependent planning deficits in PD. Interestingly, only patients in the OFF medication state showed greater deceleration in the late phase (i.e., just before the obstacle) (F(1,37)=45.42, p<0.001), as well as an increase in step time variability (also in this late phase) with the additional demands of a dual task (F(2,74)=3.49, p=0.035). Only gait deceleration between approaching phases improved with dopaminergic treatment (F(1,18)=59.20; p<0.001). Although groups showed different walking behaviors, gaze behaviors were the same for all participants, in that they planned for the obstacle more so in the early phase (p<0.05), and fixations were reduced across participants with the presence of the dual task (p<0.001). Surprisingly, the gaze behavior of the PD OFF group showed no interactions with phase or condition suggesting that the deceleration and increased variability when approaching an obstacle is the result of a greater demand for online sensory feedback that cannot be compensated for with visual strategies. We conclude that dopamine influences planning by limiting sensorimotor processing capacity, especially in the presence of increased cognitive demand in PD.

Changes in c-erbB-2 Immunoexpression in Feline Endometrial Adenocarcinomas.

Human epidermal growth factor receptor type 2 (c-erbB-2), an oncoprotein with potential prognostic marker and therapeutic use, is overexpressed in several human and animal tumours. But information regarding this molecule in feline tumours is scarce. This study aimed to assess the changes in the immunohistochemical expression of c-erbB-2 in feline endometrial adenocarcinomas (FEA) compared to normal endometrium. An immunohistochemistry assay using a specific antibody against c-erbB-2 was performed in FEA samples (n = 34) and in normal endometrium in the follicular (FS; n = 12) and luteal (LS; n = 11) stages. In FEA, the c-erbB-2 immunoexpression was assessed in neoplastic epithelial cells whilst in normal endometria it was individually evaluated in the surface and the superficial and deep glandular epithelia (SE, SGE and DGE, respectively). In FS and in LS, all the epithelia were positive for c-erbB-2; positivity was higher in the SE and the SGE than in DGE. Twenty of the 34 FEA samples (58.8%) were positive for c-erbB-2 immunolabelling. Nevertheless, its expression was higher in all the epithelia in the FS compared to FEA (p ≤ 0.0001) or the LS (p = 0.016). The results presented herein suggest that c-erbB-2 molecule is differently expressed in the feline endometrium through the oestrous cycle and though it may also be involved in feline endometrial carcinogenesis, a question remains unanswered on the importance of additional pathways of epithelial proliferation in the neoplastic changes in feline endometrium.

Genome-Wide Screening of mRNA Expression in Leprosy Patients.

Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified 1580 differentially expressed mRNAs [Fold Change (FC) ≥ 2.0, p ≤ 0.05] in diseased lesions vs. healthy controls. Some of these genes were observed in all forms of the disease (CD2, CD27, chit1, FA2H, FAM26F, GZMB, MMP9, SLAMF7, UBD) and others were exclusive to reactional forms (Type "1" reaction: GPNMB, IL1B, MICAL2, FOXQ1; Type "2" reaction: AKR1B10, FAM180B, FOXQ1, NNMT, NR1D1, PTX3, TNFRSF25). In literature, these mRNAs have been associated with numerous pathophysiological processes and signaling pathways and are present in a large number of diseases. The role of these mRNAs maybe studied in the context of developing new diagnostic markers and therapeutic targets for leprosy.

Efficacy and Safety of 2% and 4% Articaine for Lower Third Molar Surgery.

This double-blind crossover randomized clinical trial compared the efficacy of 2 concentrations of articaine, 2% (A2) and 4% (A4), with 1:200,000 epinephrine, for lower third molar removal. During 2 separate appointments with either A2 or A4, both similarly positioned lower third molars in 46 volunteers were extracted. The following were evaluated: onset and duration of anesthetic action on soft tissues, intraoperative bleeding, hemodynamic parameters, postoperative analgesia, and mouth opening and wound healing during the 7th postoperative day, along with the incidence, type, and severity of adverse reactions. Nearly identical volumes of both anesthetic solutions were used for each appointment: 3.4 ± 0.9 mL ≈ 68 mg of articaine (A2) and 3.3 ± 0.8 mL ≈ 132 mg of articaine (A4). Statistical analysis indicated no differences in onset or duration of anesthetic action on soft tissues or duration of postoperative analgesia evoked by A2 and A4 anesthetic solutions (P > 0.05). The surgeon's rating of intraoperative bleeding was considered minimal throughout all surgery with both anesthetic solutions. While transient changes in blood pressure, heart rate, and oxygen saturation were observed, these factors were clinically insignificant and were uninfluenced by articaine concentration (P > 0.05). No systemic or local adverse reactions were observed in the preoperative and postoperative periods due to A2 or A4, but 1 case of bilateral paresthesia was observed. There were no significant differences between preoperative and postoperative (7th day) values of mouth opening and wound healing whether volunteers received A2 or A4 (P > 0.05). In conclusion, both A2 and A4, administered in equal volumes, were effective and safe during lower third molar surgery, and no significant differences were found between their efficacy and safety (ClinicalTrials.gov NCT02457325).

Antiulcerogenic Activity and Toxicity of Bauhinia holophylla Hydroalcoholic Extract.

Several species of Bauhinia are used in traditional medicine for the treatment of gastrointestinal diseases, diabetes, and inflammation, among other conditions. The aim of this study was to investigate the antiulcer effect of a hydroalcoholic extract from the leaves of B. holophylla. The chemical profile of the extract was determined by HPLC-PAD-ESI-IT-MS. A dose-effect relation was constructed using the ethanol-induced gastric ulcer model in male Wistar rats. Histological analyses and studies of antioxidant and anti-inflammatory activities were performed in stomach samples. The involvement of SH compounds, NO, K(+) ATP channels, and α 2-adrenergic receptors in the gastroprotective effect was evaluated. A toxicity study was performed with a single oral dose of 5000 mg/kg. The extract was composed mainly of cyanoglucoside and flavonol-O-glycosides derivatives of quercetin and myricetin. SH compounds, NO release, K(+) ATP channel activation, and presynaptic α 2-adrenergic receptor stimulation each proved to be involved in the antiulcer effect. The levels of GSH and activity of GR and GPx were increased, and the levels of TNF-α, IL-6 and IL-10 were modulated. There was an antidiarrheal effect and there were no signs of toxicity. B. holophylla presents antiulcer activity mainly by decreasing oxidative stress and attenuating the inflammatory response, without inducing side effects.

Neutron spectra due (13)N production in a PET cyclotron.

Monte Carlo and experimental methods have been used to characterize the neutron radiation field around PET (Positron Emission Tomography) cyclotrons. In this work, the Monte Carlo code MCNPX was used to estimate the neutron spectra, the neutron fluence rates and the ambient dose equivalent (H*(10)) in seven locations around a PET cyclotron during (13)N production. In order to validate these calculations, H*(10) was measured in three sites and were compared with the calculated doses. All the spectra have two peaks, one above 0.1MeV due to the evaporation neutrons and another in the thermal region due to the room-return effects. Despite the relatively large difference between the measured and calculated H*(10) for one point, the agreement was considered good, compared with that obtained for (18)F production in a previous work.

Visual cues and gait improvement in Parkinson's disease: which piece of information is really important?

Visual exproprioception refers to information of the body relative to the environment and may be the critical piece of sensory information that explains why gait improvements can be achieved with visual step cues in people with Parkinson's disease (PD). The primary aim of current study was to investigate the role of visual exproprioception in the positive effect of visual cues on gait in patients with PD. Nineteen individuals with PD and 15 healthy subjects participated in this study. Four conditions of self-paced gait were tested: normal walking, without exproprioception (exproprioceptive information of lower limbs removed), visual step length cues, and visual step length cues but without exproprioception. Gaze behavior, gait parameters and the accuracy and precision of foot placement on the visual cues were recorded. Individuals with PD improved step length in both cued conditions. Both groups fixated close to 46% on visual cues necessary to accomplish the next step (ongoing step), while 54% of fixations were focused on visual cues one or more steps ahead. Also, both groups increased absolute error and error variability of the foot placement around the visual cues without vision of their feet. These results suggest that exproprioceptive information is not critical to achieve step length and overall gait benefits with visual cues in PD, but is critical for the accuracy and precision of foot placement on targets. People with PD and healthy individuals use visual information from visual cues in both on-line and feedforward fashions. In conclusion, patients with PD likely focus attention on the discrete goal of each foot hitting a visual cue placed on the floor and then use the exteroceptive information (i.e. position of next foot placement location) to plan each step individually at a cortical level.