Test station to characterize the emission of a LiDAR.

A test station setup devised to measure the emission characteristics and beam propagation parameters of a light detection and ranging (LiDAR) system is presented. The main blocks of the station to measure the accessible emission, wavelength peak and FWHM, pulse duration, pulse repetition rate, horizontal and vertical angular resolution, field of view, beam propagation factor M 2, beam waist size, waist location, and divergence are described. The performance of this test station was demonstrated using a commercial spinning LiDAR, a Velodyne VLP-16, which successfully enables these measurements for a laser beam with a wavelength of 913 nm.

Assessment of Volumetric Dense Tissue Segmentation in Tomosynthesis Using Deep Virtual Clinical Trials.

The adoption of artificial intelligence (AI) in medical imaging requires careful evaluation of machine-learning algorithms. We propose the use of a "deep virtual clinical trial" (DeepVCT) method to effectively evaluate the performance of AI algorithms. In this paper, DeepVCTs have been proposed to elucidate limitations of AI applications and predictions of clinical outcomes, avoiding biases in study designs. The DeepVCT method was used to evaluate the performance of nnU-Net models in assessing volumetric breast density (VBD) from digital breast tomosynthesis (DBT) images. In total, 2,010 anatomical breast models were simulated. Projections were simulated using the acquisition geometry of a clinical DBT system. The projections were reconstructed using 0.1, 0.2, and 0.5 mm plane spacing. nnU-Net models were developed using the center-most planes of the reconstructions with the respective ground-truth. The results show that the accuracy of the nnU-Net improves significantly with DBT images reconstructed with 0.1 mm plane spacing (78.4×205.3×40.1 mm3). The segmentations resulted in Dice values up to 0.84 with area under the receiver operating characteristic curve of 0.92. The optimization of plane spacing for VBD assessment was used as an exemplar of a DeepVCT application, allowing us to interpret better the input parameters and outcomes of the nnU-Net. Thus, DeepVCTs can provide a plethora of evidence to predict the efficacy of these algorithms using large-scale simulation-based data.

Relevance of the diagnosis of hypersensitivity reactions to antineoplastic and biological agents: experience with drug provocation test.

Summary: Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive (platins (n = 6), doxorubicin (n = 1)). Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.

Consumer Profile Segmentation in Online Lottery Gambling Utilizing Behavioral Tracking Data from the Portuguese National Lottery.

The present study is the first to examine account-based tracking data of Portuguese online lottery players comprising the gambling activity of all active players over a one-year period (N = 154,585). The main research goal was the identification of groups or segments of players by their engagement levels (high, neutral, low) and to assess preferences in product category with the use of CHAID (Chi-Square Automatic Interaction Detection) segmentation models, based on expenditure and sociodemographic variables. Findings showed that (1) age was found to be the most influential differentiating variable in player segmentation and had a positive correlation with expenditures and wagers, (2) gender was the second most influential variable (males represented 78.7% of players), (3) education the third most influential variable and had a negative correlation with expenditure, and (4) region was the least relevant variable. The models generated several players segments that engaged in different games. Older males (54-64 years; ≥ 65 years) were the most engaged overall. Younger males (18-34 years) were the least engaged but showed preferences for lotto as did females (35-49 years). Lower educated males and older males (49 years+) with a high school education were the most engaged in instant lottery games. These findings show that Portuguese lottery players can be grouped into several segments with distinct demographic characteristics and corresponding engagement levels. These findings help support more effective marketing segmentation and will help in the targeting of responsible gambling approaches.

A Mixed Methods Population Health Approach to Explore Radon-Induced Lung Cancer Risk Perception in Canada.

BACKGROUND: Radon is a predominant indoor air pollutant and second leading cause of lung cancer in radon-prone areas. Despite the gravity of the health risk, residents in Canada have inadequate perception and taken minimal protective actions. Better perception of a risk motivates people to take preventive measures. Scholarship about radon health risk perception is lacking in Canada. We applied a mixed methods population health approach to explore the determinants shaping perception and actions of a resident population in Canada. METHODS: We conducted mixed surveys (n = 557) and qualitative bilingual interviews (n = 35) with both homeowners and tenants of Ottawa-Gatineau areas. The study explored residents' risk perception and adaptations factors. Descriptive, correlational and regression analyses described and established associations between quantitative variables. Thematic, inductive analyses identified themes in the qualitative data. A mixed methods analysis triangulated both results to draw a holistic perception of the health risk. RESULTS: Residents' quantitative perceptions of radon health risk, smoking at home, synergistic risk perception, social influence and care for family were associated significantly with their intention to test for radon levels in their home, actual testing and mitigation. These results were explained further with the qualitative findings. Residents who had dual cognitive and emotional awareness of the risk were motivated enough to take preventive actions. Caring for family, knowing others who contracted lung cancer and financial capability were enablers, whereas lack of awareness and homeownership, cost of mitigation and stigma were obstacles to preventive actions. We also explored the dual subjective and objective aspects of risk perception that are influenced by micro- and macro-level determinants. CONCLUSIONS: Inducing protective action to reduce risk requires comprehensive population-level interventions considering dual perceptions of the risk that can modify the risk determinants. Future research can explore the dual aspects of risk perception and unequal distribution of the risk factors.

Low-dimensional chaos in the single wave model for self-consistent wave-particle Hamiltonian.

We analyze nonlinear aspects of the self-consistent wave-particle interaction using Hamiltonian dynamics in the single wave model, where the wave is modified due to the particle dynamics. This interaction plays an important role in the emergence of plasma instabilities and turbulence. The simplest case, where one particle (N=1) is coupled with one wave (M=1), is completely integrable, and the nonlinear effects reduce to the wave potential pulsating while the particle either remains trapped or circulates forever. On increasing the number of particles ( N=2, M=1), integrability is lost and chaos develops. Our analyses identify the two standard ways for chaos to appear and grow (the homoclinic tangle born from a separatrix, and the resonance overlap near an elliptic fixed point). Moreover, a strong form of chaos occurs when the energy is high enough for the wave amplitude to vanish occasionally.

Deformable liposomes as enhancer of caffeine penetration through human skin in a Franz diffusion cell test.

OBJECTIVE: The permeation of hydrophilic molecules through the skin is still a challenge due to the barrier posed by stratum corneum, the outermost layer of the skin. Liposomes have frequently been used as carriers for different types of drugs and may also function as permeation enhancers. Propylene glycol has also been used as an edge activator in liposomes to increase the permeation. The aim of this work was to prepare liposomes containing an edge activator and loaded with caffeine to evaluate the potential of caffeine reaching the deeper layers in the skin. METHODS: The formulations were prepared by a top-down process using high-pressure homogenization at 200 00 psi for 10 min. They were characterized by size, polydispersity index (PI), zeta potential (ZP), pH, caffeine content and encapsulation efficiency (EE%) on preparation (time zero) and after 30 days. Cytotoxicity of blank and loaded liposomes was assessed by MTT proliferation assay with a normal keratinocyte cell line (HaCaT). In vitro permeation tests were performed with human skin in Franz cells over 24 h, and caffeine concentration was determined in the skin surface, stratum corneum, dermo-epidermal fraction and receptor medium by HPLC. RESULTS: The caffeine liposomes with (DL-Caf) or without propylene glycol (CL-Caf) showed, respectively, mean size 94.5 and 95.4 nm, PI 0.48 and 0.42, ZP + 1.3 and + 18.1 mV and caffeine content of 78.57 and 80.13%. IC50 values of caffeine in DL-Caf (3.59 v/v %) and CL-Caf (3.65 v/v %) were not significantly different from conventional blank liposome (3.27 v/v %). The DL-Caf formulation presented the best capability to enhance the caffeine permeation through the skin, resulting 1.94-folds higher than caffeine solution. Furthermore, the caffeine flux from DL-Caf was 1.56- and 3.05-folds higher than caffeine solution and CL-Caf, respectively. On the other hand, CL-Caf showed the lowest caffeine penetration revealing the importance of edge activator to aid hydrophilic drug penetration to all skin layers. CONCLUSION: The DL-Caf formulation tested was able to improve the permeation of caffeine through the stratum corneum and dermo-epidermal layers, suggesting that this delivery system may be effective for deep skin delivery of hydrophilic drugs.

OBJECTIF: La perm´eation de mol´ecules hydrophiles `a travers lapeau reste un d´efi en raison de la barri`ere oppos´ee par la couchecorn´ee, la couche la plus externe de la peau. Les liposomes ontfr´equemment ´et´e utilis´es comme supports pour diff´erents types dem´edicaments et peuvent ´egalement fonctionner comme des amplificateursde perm´eation. Le propyl`ene glycol a ´egalement ´et´e utilis´ecomme activateur dans les liposomes pour augmenter la perm´eation.Le but de ce travail ´etait de pr´eparer des liposomes contenantun activateur et charg´es de caf´eine pour ´evaluer le potentiel de lacaf´eine atteignant les couches les plus profondes de la peau. MÉTHODES: Les formulations sont pr´epar´ees par homog´en´eisationhaute pression `a 200 00 psi pendant 10 min. Elles sontcaract´eris´es par la taille des liposomes, l'indice de polydispersit´e(PI), le potentiel zˆeta (ZP), le pH, la teneur en caf´eine et l'efficacit´ed'encapsulation (EE%) `a la pr´eparation (temps z´ero) et apr`es 30jours. La cytotoxicit´e des liposomes `a blanc et charg´es est ´evalu´eepar un test de prolif´eration MTT avec une lign´ee cellulaire de k´eratinocytesnormale (HaCaT). Des tests de perm´eation in vitro sontr´ealis´es avec de la peau humaine dans des cellules de Franz pendant24 h, et la concentration de caf´eine est d´etermin´ee `a la surfacede la peau, dans la couche corn´ee, la fraction dermo-´epidermique et le milieu r´ecepteur par HPLC. RÉSULTATS: Les liposomes contenant de la caf´eine avec (DL-Caf)ou sans propyl`ene glycol (CL-Caf) pr´esentent respectivement unetaille moyenne de 94,5 et 95,4 nm, PI 0,48 et 0,42, ZP + 1,3 et +18,1 mV et une teneur en caf´eine de 78,57 et 80,13%. Les valeursIC50 de la caf´eine dans DL - Caf (3,59 %v/v) et CL - Caf (3,65 %v/v) ne sont pas significativement diff´erentes de celles du liposome `ablanc conventionnel (3,27 %v/v). La formulation DL-Caf est cellequi permet la meilleure perm´eation de la caf´eine, avec une quantit´ede caf´eine dans la peau 1,94 fois plus ´elev´ee que la solution decaf´eine. De plus, le flux de caf´eine de DL-Caf est 1,56 et 3,05 foisplus ´elev´e que la solution de caf´eine et CL-Caf, respectivement.D'autre part, CL-Caf montre la plus faible p´en´etration de caf´eine,r´ev´elant l'importance de l'activateur pour aider `a la p´en´etration dela mol´ecule hydrophile dans toutes les couches de la peau. CONCLUSION: La formulation DL-Caf test´ee am´eliore la perm´eationde la caf´eine `a travers la couche corn´ee et les couches dermo-´epidermiques, ce qui sugg`ere que ce syst`eme d'administration peutˆetre efficace pour l'administration cutan´ee profonde de mol´eculeshydrophiles.

Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Canine parvovirus: a predicting canine model for sepsis.

BACKGROUND: Sepsis is a severe condition associated with high prevalence and mortality rates. Parvovirus enteritis is a predisposing factor for sepsis, as it promotes intestinal bacterial translocation and severe immunosuppression. This makes dogs infected by parvovirus a suitable study population as far as sepsis is concerned. The main objective of the present study was to evaluate the differences between two sets of SIRS (Systemic Inflammatory Response Syndrome) criteria in outcome prediction: SIRS 1991 and SIRS 2001. The possibility of stratifying and classifying septic dogs was assessed using a proposed animal adapted PIRO (Predisposition, Infection, Response and Organ dysfunction) scoring system. RESULTS: The 72 dogs enrolled in this study were scored for each of the PIRO elements, except for Infection, as all were considered to have the same infection score, and subjected to two sets of SIRS criteria, in order to measure their correlation with the outcome. Concerning SIRS criteria, it was found that the proposed alterations on SIRS 2001 (capillary refill time or mucous membrane colour alteration) were significantly associated with the outcome (OR = 4.09, p < 0.05), contrasting with the 1991 SIRS criteria (p = 0.352) that did not correlate with the outcome. No significant statistical association was found between Predisposition (p = 1), Response (p = 0.1135), Organ dysfunction (p = 0.1135), total PIRO score (p = 0.093) and outcome. To explore the possibility of using the SIRS criteria as a fast decision-making tool, a Fast-and-Frugal tree (FFT) was created with a sensitivity of 92% and a specificity of 29%. CONCLUSION: These results suggest that increasing the SIRS criteria specificity may improve their prognostic value and their clinical usefulness. In order to improve the proposed PIRO scoring system outcome prediction ability, more specific criteria should be added, mainly inflammatory and organ dysfunction biomarkers.

RAR-Related Orphan Receptor Gamma T (RoRγt)-Related Cytokines Play a Role in Neutrophil Infiltration of the Central Nervous System After Subarachnoid Hemorrhage.

BACKGROUND: How inflammatory cells are recruited into the central nervous system is a topic of interest in a number of neurological injuries. In aneurysmal subarachnoid hemorrhage (SAH), neutrophil accumulation in the central nervous system 3 days after the hemorrhage is a critical step in the development of delayed cerebral injury (DCI). The mechanism by which neutrophils enter the central nervous system is still unclear. METHODS AND RESULTS: To identify human effectors of neutrophil recruitment, cerebrospinal fluid (CSF) samples were taken from a small, selected sample of SAH patients with external ventricular drainage devices (10 patients). Among a battery of CSF cytokines tested 3 days after SAH, five cytokines were associated with poor 90-day outcome (modified Rankin Score 3-6). A parallel study in a mouse model of mild SAH showed elevation in three cytokines in the CNS compared to sham. IL-17 and IL-2 were increased in both patients and the mouse model. IL-17 was investigated further because of its known role in neutrophil recruitment. Inhibition of RAR-Related Orphan Receptor Gamma T, the master transcription factor of IL-17, with the inverse agonist GSK805 suppressed neutrophils entry into the CNS after SAH compared to control. Using an IL-17 reporter mouse, we investigated the source of IL-17 and found that myeloid cells were a common IL-17-producing cell type in the meninges after SAH, suggesting an autocrine role for neutrophil recruitment. CONCLUSIONS: Taken together, IL-17 appears to be in important factor in the recruitment of neutrophils into the meninges after SAH and could be an important target for therapies to ameliorate DCI.

Electrochemical dissolution of nickel-titanium instrument fragments in root canals of extracted human maxillary molars using a small reservoir of electrolyte.

AIM: To evaluate the viability of the electrochemical dissolution of fragments of fractured NiTi instruments in root canals of extracted human maxillary molars, using two electrodes and the solution restricted to a small reservoir coupled to the pulp chamber. The primary hypothesis was that this method enables the reduction of fragment volume and re-establishment of the root canal path with a size 08 K-file, both in simulated canals and in extracted human maxillary molars. METHODOLOGY: Fragments of F1 ProTaper instruments were polarized in simulated root canals and in distobuccal root canals of extracted maxillary molars using a new method, with the solution restricted to a small acrylic microcell coupled to each resin block or pulp chamber. Two electrodes were used, where one was kept in contact with the intracanal fragment and another was positioned in the solution present in the acrylic microcell. After the tests, a size 08 K-file was used passively to verify the possibility of bypassing the fragment, which was also confirmed by radiographic analysis. Micro-CT analysis of the teeth was used before and after fragment dissolution to evaluate the volume, length and porosity of the fragments. The D'Agostino-Pearson normality test was used to verify the distribution of the data. A paired t-test (P < 0.05) was used to compare the volume, length and porosity of the fragments before and after the dissolution tests. RESULTS: After dissolution, all fragments could be bypassed with a size 08 K-file in both simulated canals and in extracted teeth. The dissolution process did not result in significant reduction of neither the fragment length nor the fragment porosity. However, it resulted in a significant reduction of fragment volume (paired t-test, P < 0.05). CONCLUSION: The electrochemical dissolution of fragments of NiTi files in root canals of extracted human maxillary molars using two electrodes, and the solution restricted to a small reservoir coupled to the pulp chamber resulted in a significant reduction of fragment volume. The re-establishment of the root canal path with the passive insertion of size 08 K-files was possible in all samples after the tests, both in simulated canals and in extracted teeth.

Generation of 35 kW peak power 80 fs pulses at 2.9 µm from a fully fusion-spliced fiber laser.

Tunable femtosecond light sources in the short wave and middle wave infrared regions are of utmost importance for various applications ranging from multiphoton microscopy, mid-infrared supercontinuum generation to high-harmonic generation. We report on an all-fusion-spliced fiber laser emitting 80 fs pulses up to 2.9 µm with 35 kW peak power. The laser is based on Raman self-frequency shift effect from 1560 nm up to 3000 nm in germanium-doped fibers fabricated by the widespread modified chemical vapor deposition process.

Maternal blood biomarkers and adverse pregnancy outcomes: a systematic review and meta-analysis.

Background: Pregnancy is a vulnerable period for the mother and the infant and exposures to environmental chemicals in utero can influence neonatal morbidity and mortality. There is a momentum toward understanding and exploring the current maternal biological mechanisms specific to in utero effects, to improve birth outcomes. This study aims to examine the current understanding of the role of biomarkers that may be associated with term of pregnancy, infant birth weights and infant development in utero.Methods: Electronic searches were conducted in PubMed, Embase, OvidMD, and Scopus databases; and all relevant research articles in English were retrieved. Studies were selected if they evaluated maternal blood plasma/serum biomarkers proposed to influence adverse birth outcomes in the neonate. Data were extracted on characteristics, quality, and odds ratios from each study and meta-analysis was conducted.Results: A total of 54 studies (35 for meta-analysis), including 43,702 women, 50 plasma markers and six descriptors of birth outcomes were included in the present study. The random effect point estimates for risk of adverse birth outcomes were 1.61(95%CI: 1.39-1.85, p < 0.0001) for inflammation-related biomarkers and 1.65(95%CI: 1.22-2.25, p = 0.0013) for growth factor/hormone-related biomarkers. All subgroups of plasma markers showed significant associations with adverse birth outcomes with no apparent study bias.Conclusions: The two subsets of plasma markers identified in this study (inflammation-related and growth factor/hormone-related) may serve as potentially valuable tools in the investigation of maternal molecular mechanisms, especially select pathways underlying inflammatory and immunological mediation in terms of modulating adverse infant outcomes. Future large, prospective cohort studies are needed to validate the promising plasma biomarkers, and to examine other maternal biological matrices such as cervicovaginal fluid and urine.

Cross-section profile of the nonlinear refractive index of Gorilla Glass obtained by nonlinear ellipse rotation measurements.

In this work we determined the influence of potassium-to-sodium ion exchange in the nonlinear refractive value (n2) of Corning's Gorilla Glass (GG). Due to the production process, GG has a rich potassium surface in comparison to the original sodium matrix glass. In order to determine the nonlinear cross-section profile, we have used a highly sensitive nonlinear elliptical rotation spatial measurement. Using a simple model, where the nonlinearity varies exponentially with depth, we observed that the value of the nonlinear refraction at the surface is about 22% greater than that of the matrix interior with a penetration depth constant of ∼50 µm.

Evaluation of the amount of nanoparticles emitted in LASER additive manufacture/welding.

Objectives: The objective of this study was the evaluation of the professional exposure to nanoparticles during tasks performed in workstations for production of metallic parts by laser welding additive manufacturing. Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35 µm. Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used. Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15 nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body.

Gastrointestinal parasites as a possible threat to an endangered autochthonous Portuguese sheep breed.

Helminth and protozoan infections are responsible for important diseases in grazing sheep, which can be especially threatening in an autochthonous breed at risk of extinction like the Churra Galega Mirandesa Portuguese sheep breed. The aim of the present study was to determine the diversity, prevalence and burden of gastrointestinal parasites in these sheep and to assess the effects of deworming practices, cohabiting animals on the farm and feed management. Coprological qualitative and quantitative analysis (flotation, natural sedimentation and McMaster method) were used to identify and quantify gastrointestinal parasites and a questionnaire was designed and applied. A total of 512 faecal samples were collected from 49 flocks, and 49 replies to the questionnaire were received. Parasites were identified in 100% of the flocks, and in 97% of the samples. The genera or species that have been morphologically identified were: strongyle-type, Nematodirus spp., Skrjabinema spp., Moniezia expansa, Moniezia benedeni, Trichuris spp., Capillaria spp., Eimeria spp., Dicrocoelium spp. and Fasciola hepatica. This is the first report in Portugal of Skrjabinema spp. The burden of parasites' oocysts and eggs per gram in faecal samples ranged, respectively, from 50 to 17,550 for Eimeria spp., and from 50 to 6250 for strongyle-type eggs. Factors affecting parasitic infections were evaluated using a multivariate logistic regression. Grazing time and a lack of anthelmintic treatment were positively associated with Nematodirus spp. infection. This study showed that there is a high prevalence and diversity of gastrointestinal parasites in the Churra Galega Mirandesa sheep breed.

Dual immune effect of iNKT cells considering human cutaneous and visceral leishmaniasis: An example of cell plasticity according to different disease scenarios.

Although the semi-invariant natural killer T cells (iNKT) are a small subpopulation of cells in the peripheral blood, they are presumed to play a role in early stages of infection against various pathogens, including protozoa. This work investigates the activation status and cytokine profile of iNKT cells during human Leishmania infantum and Leishmania braziliensis infection. We studied iNKT cells in patients with symptomatic active visceral leishmaniasis (AVL) (n = 8), patients with symptomatic active cutaneous leishmaniasis (ACL) (n = 13), negative endemic controls (NEC) (n = 6) and non-endemic controls (NonEC) (n = 6), with and without total Leishmania antigen stimulus (TLA). The number of iNKT cells in the peripheral blood of patients with ACL and AVL unaltered in relation to control groups. Moreover, the iNKT cells from ACL showed a hyperactivation profile compared to patients with AVL. Additionally, TLA induced IFN-gamma production in iNKT cells from patients with ACL, while in iNKT of patients with AVL, TLA induced a decrease in this cytokine. Higher IL-17 and IL-10 production by iNKT cells from patients with ACL were also observed compared to all other groups. There were no changes in iNKT IL-10-producing cells in AVL after TLA stimulation. However, TLA induced increase in IL-10 in iNKT cells in patients with ACL. These findings suggest that, although iNKT cells showed distinct profiles in patients with ACL and AVL, they play a dual role in immune modulation in both Leishmania infections.

Two-photon microscopy with a frequency-doubled fully fusion-spliced fiber laser at 1840 nm.

We introduce a fiber-based laser system providing 130 fs pulses with 3.5 nJ energy at 920 nm at a 43 MHz repetition rate and illustrate the potential of the source for two-photon excited fluorescence microscopy of living mouse brain. The laser source is based on frequency-doubling high-energy solitons generated and frequency-shifted to 1840 nm in large mode area fibers. This simple laser system could unleash the potential of two-photon microscopy techniques in the biology laboratory where green fluorescent proteins with two-photon absorption spectrum peaking around 920 nm are routinely used.

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.

Effects of loss of occlusal contact on the expression of matrix metalloproteinase-2, membrane type 1-MMP, tissue inhibitor of the MMP-2, eruption rate, organization and resistance of collagen fibers of the rat incisor periodontal ligament.

BACKGROUND AND OBJECTIVE: This study investigated the effect of occlusal contact loss (induced by tooth shortening), on matrix metalloproteinase (MMP)-2, membrane type 1-MMP (MT1-MMP) and tissue inhibitor of the MMP-2 (TIMP-2) expressions in the periodontal ligament of the rat incisor, as well as eruption rate, resistance and collagen organization. MATERIAL AND METHODS: Male Wistar rats were distributed into a control group, denominated normofunctional group, whose lower teeth underwent a normal eruption process; and a hypofunctional group, whose lower left incisor teeth were shortened every 2 days during 14 days. Parameters were evaluated on the first, seventh and 14th days and the eruption rate was determined according to the size of the incisor during the eruption process. MMP-2 activity was determined by zymography and the expressions of the MT1-MMP and TIMP-2 proteins were quantitated by western blot. Collagen protein organization, as indicated by the birefringence of the periodontal ligament, was analyzed under polarized light and the periodontal ligament's resistance was determined from the load necessary to inject the incisor into its alveolar space, before extraction. RESULTS: Loss of occlusal contact, in rats submitted to hypofunctional eruption, increased MMP-2 activity and eruption rate, but decreased MT1-MMP and TIMP-2 expression and disrupted collagen organization in the periodontal ligament, consequently reducing periodontal ligament resistance. CONCLUSION: We conclude that, after incisor eruption, occlusal contact may be an important factor for regulating the remodeling and the physiological resistance of the periodontal ligament against the continuous eruption process observed in rat incisors.