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Purpose: To investigate whether genetic variations in cytokine genes involved in the pathogenesis of peri-implantitis are associated with the occurrence of peri-implantitis, an issue that remains controversial and may vary according to the population evaluated., Materials and Methods: A cross-sectional analytical study was carried out on 102 Caucasian Portuguese individuals who were divided into two groups: (1) 43 individuals with peri-implantitis and (2) 59 individuals with good peri-implant health. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR for IL-1RN., Results: The IL-1A-889 C/T polymorphism presented with a higher prevalence of the less common allele (T allele) in patients with peri-implantitis (27.9%) than in healthy patients (16.9%), but without statistical significance (P = .060). For the IL-1B+3954 C/T and IL-1RN (variable number of tandem repeats [VNTR]) polymorphisms, analysis revealed that the allele and genotype frequencies did not differ significantly between groups. There was a significant association between a history of periodontitis and peri-implantitis (P = .020)., Conclusions: The evaluated genetic polymorphisms had no influence on the occurrence of peri-implantitis in the study population. Further research into genetic variations in different populations is needed to elucidate the role of genetic factors in the onset and progression of peri-implant disease.

Background: The piriform cortex (PC) occupies both banks of the endorhinal sulcus and has an important role in the pathophysiology of temporal lobe epilepsy (TLE). A recent study showed that resection of more than 50% of PC increased the odds of becoming seizure free by a factor of 16., Objective: We report the feasibility of manual segmentation of PC and application of the Geodesic Information Flows (GIF) algorithm to automated segmentation, to guide resection., Methods: Manual segmentation of PC was performed by two blinded independent examiners in 60 patients with TLE (55% Left TLE, 52% female) with a median age of 35 years (IQR, 29-47 years) and 20 controls (60% Women) with a median age of 39.5 years (IQR, 31-49). The GIF algorithm was used to create an automated pipeline for parcellating PC which was used to guide excision as part of temporal lobe resection for TLE., Results: Right PC was larger in patients and controls. Parcellation of PC was used to guide anterior temporal lobe resection, with subsequent seizure freedom and no visual field or language deficit., Conclusion: Reliable segmentation of PC is feasible and can be applied prospectively to guide neurosurgical resection that increases the chances of a good outcome from temporal lobe resection for TLE.

Objective: Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. .Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats., Methodology: To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression., Results: All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points., Conclusion: Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.

The aim of this study was to evaluate the possible relationships between polymorphisms in the interleukin-1 ( IL-1 ) A , IL-1B , and IL-1RN genes and concentrations of the inflammatory mediators IL-1β, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) in peri-implant crevicular fluid (PICF). A cross-sectional analytical study was conducted on 51 patients with dental implants. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR and restriction fragment length polymorphism analysis for IL-1RN . For the biochemical analysis, the concentrations of IL-1β and TNF-α were analyzed using multiplexed fluorescent sphere immunoassays, and PGE2 by enzyme-linked immunosorbent assay. In patients with detected IL-1RN polymorphism, there was an increase in the concentration of the three mediators with statistically significant differences in the mean values of TNF-α and PGE2, regardless of peri-implant health status ( p = 0.002 and p = 0.049, respectively). The concentrations of all three mediators were positively and significantly correlated (IL-1β vs. TNF-α Rho = 0.480, p < 0.001; IL-1β vs. PGE2 Rho = 0.382, p = 0.006; and TNF-α vs. PGE2 Rho = 0.528, p < 0.001). We can conclude that the IL-1RN polymorphism exerts an influence on the PICF immune response, which may explain the influence of this genetic polymorphism on the occurrence of peri-implantitis.

Background and Objective: Bidimensional entropy algorithms provide meaningful quantitative information on image textures. These algorithms have the advantage of relying on well-known one-dimensional entropy measures dedicated to the analysis of time series. However, uni- and bidimensional algorithms require the adjustment of some parameters that influence the obtained results or even findings. To address this, ensemble entropy techniques have recently emerged as a solution for signal analysis, offering greater stability and reduced bias in data patterns during entropy estimation. However, such algorithms have not yet been extended to their two-dimensional forms., Methods: We therefore propose six bidimensional algorithms, namely ensemble sample entropy, ensemble permutation entropy, ensemble dispersion entropy, ensemble distribution entropy, and two versions of ensemble fuzzy entropy based on different models or parameters initialization of an entropy algorithm. These new measures are first tested on synthetic images and further applied to a biomedical dataset., Results: The results suggest that ensemble techniques are able to detect different levels of image dynamics and their degrees of randomness. These methods lead to more stable entropy values (lower coefficients of variations) for the synthetic data. The results also show that these new measures can obtain up to 92.7% accuracy and 88.4% sensitivity when classifying patients with pulmonary emphysema through a k-nearest neighbors algorithm., Conclusions: This is a further step towards the potential clinical deployment of bidimensional ensemble approaches to detect different levels of image dynamics and their successful performance on emphysema lung computerized tomography scans. These bidimensional ensemble entropy algorithms have potential to be used in various imaging applications thanks to their ability to distinguish more stable and less biased image patterns compared to their original counterparts., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andreia S. Gaudencio reports a relationship with Foundation for Science and Technology that includes: funding grants. Andreia S. Gaudencio reports a relationship with European Social Fund that includes: funding grants., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Surgical procedures, radiotherapy, and chemotherapy, individually or in association, are current oncological treatments. Among the most used chemotherapy drugs, 5-fluorouracil (5FU) is an antimetabolite with a broad spectrum of action. This study evaluated the effects of probiotics (PRO) as an adjuvant to the treatment of experimental periodontitis (EP) in rats immunosuppressed with 5FU.108 rats were randomly allocated to six different groups: EP; SS - systemic treatment with saline solution (SS); 5FU - systemic treatment with 5FU; 5FU+PRO - systemic treatment with 5FU, followed by the local administration of Saccharomyces cerevisiae ; 5FU+SRP - systemic treatment with 5-FU, followed by scaling and root planing (SRP); and 5FU+SRP+PRO - systemic treatment with 5FU followed by local treatments with SRP and PRO. Immunosuppression was obtained at two points: at the time of ligature installation and after 48 h. Six animals from each group were euthanized at seven, 15, and 30 d and hemimandibles were collected and processed for histopathological, histometric, and immunohistochemical analysis. Data were subjected to statistical analysis (α=5%). At 7 d, the 5FU+PRO group showed less bone resorption and better structured connective tissue compared with the EP, SS, 5FU+SRP, and 5FU+SRP+PRO groups. At 15 d, the 5FU+SRP group showed a greater intensity of the inflammatory response (p<0.05). At 30 d, the 5FU+SRP+PRO group showed better structured bone tissue and a higher percentage of bone tissue (PBT) than the EP, SS, 5FU, and 5FU+PRO groups (p<0.05). The use of Saccharomyces cerevisiae as monotherapy or as an adjuvant to periodontal therapy may have a positive effect on bone repair in immunosuppressed conditions.

Background: Bronchobiliary fistula is a rare and complex entity defined by an abnormal communication between the biliary and bronchial systems. The etiopathogenesis is not completely understood, but the most common factors implicated are hepatobiliary tumors, biliary obstruction, iatrogenic damage or trauma., Methods: Here we present a case of a 69-year-old man that developed a bronchobiliary fistula and a pulmonary abscess after migration of a bile duct stent placed as part of the treatment of an iatrogenic bile duct injury that occurred during elective cholecystectomy., Results: A conservative approach, that included broad-spectrum antibiotic, removal of the stent, and sphincterotomy, was enough for the closure of the fistula and resolution of the symptoms., Conclusion: We emphasize the importance of prompt recognition of this entity and a concerted therapeutic strategy to optimize the probability of success, avoiding the destructive consequences of the bile in the pulmonary parenchyma and septic complications.

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8 + T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4 + T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8 + T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production., (© 2023. The Author(s).)

Dogs are the most common domestic reservoir of Leishmania infantum, making canine visceral leishmaniasis (CVL) a serious public health issue. Identifying new methodologies that can mimic lymphoid and myeloid competence in naturally infected dogs could lower costs and save time in preliminary screenings of potential immunotherapeutic agents and vaccines against CVL. For that, we established a cell-to-cell communication approach between lymphocytes and myeloid cells from healthy, asymptomatic (infected, without apparent clinical signs) and symptomatic (infected with apparent clinical signs) dogs. Peripheral blood mononuclear cells (PBMC) from these dogs were used as source of CD4 + , CD8 + T lymphocytes and macrophages, that were posteriorly infected with L. infantum GFP + promastigotes (green fluorescent protein). Macrophages co-cultured with purified lymphocytes were tested for the ability to control cellular parasitism, and their microbicidal function by producing nitric oxide (NO) and reactive oxygen species (ROS). The kind of T cell response within the co-culture was also evaluated, by assessing their ability to produce interferon-gamma (IFN-γ) and interleukin 4 (IL-4). The data suggests that T lymphocytes from symptomatic dogs are more prone to produce IL-4 than the ones from asymptomatic dogs. Macrophages from asymptomatic dogs also demonstrated a higher microbicidal potential, with increased levels of NO and ROS production, compared to symptomatic dogs, mainly in highly parasitized cells. Together, our results identify the ratio of IL-4/IFN-γ produced by CD4 + and CD8 + T cells, as well as, the ratio between parasite GFP signal/NO and ROS signal in macrophages as potential immunological biomarkers of failure and success of the screened agents. Our findings also propose a reliable methodology that can be used to follow the immune response in trials of potential drugs or vaccines targeting CVL., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the effects of probiotic (PRO) Lactobacillus reuteri (DSM17938) as an adjuvant to the treatment of experimental periodontitis (EP)., Material and Methods: Fifty-four male adult Wistar rats were included. EP was induced and maintained for 7 days. Subsequently, the ligature was removed and the animals were allocated into three different experimental groups (n = 18/group): EP - no local treatment, the animals received four systemic saline solution (SS) administrations; SRP+SS, the animals underwent SRP treatment, followed by SS administration; and SRP+PRO, the animals received SRP treatment, followed by the systemic administration of PROs ( Lactobacillus reuteri ; 0.16 ml/day). Six animals from each group were euthanised at 7, 15 and 30 days. Histological and histometric analyses of alveolar bone loss (BL) and immunohistochemical analyses for TRAP, RANKL, OPG, OCN, and PCNA were performed. Shapiro-Wilk, ANOVA, post-hoc Tukey, Kruskal-Wallis, Student-Newman Keuls were performed., Results: The SRP+PRO group presented a reduction in inflammation. At 15 days, a lower BL was observed in the SRP+SS and SRP+PRO groups. Greater immunolabeling was noticed for PCNA at 15 days in the SRP+PRO group than in the SRP + SS group. The SRP+PRO group demonstrated a higher OCN immunolabeling pattern than the EP group at 15 and 30 days., Conclusion: The use of Lactobacillus reuteri as an adjuvant to SRP for the treatment of EP showed promising results in the control of local inflammatory responses, and enhanced the periodontal tissue repair process according to the employed concentration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.)

The spleen plays a central role in human and canine visceral leishmaniasis, where the activation of the immune response occurs in one of the tissues where Leishmania infantum reproduces. Therefore, this organ is both a target to understand the mechanisms involved in the parasite control and a parameter for assessing the therapeutic response. In this sense, this study aimed to evaluate the main histological, immunological and parasitological aspects in the spleen of symptomatic dogs naturally infected by L. infantum treated with the therapeutic vaccine LBMPL. For this, dogs were divided into four groups: dogs uninfected and untreated (NI group); L. infantum -infected dogs that were not treated (INT group); L. infantum -infected dogs that received treatment only with monophosphoryl lipid A adjuvant (MPL group); and L. infantum -infected dogs that received treatment with the vaccine composed by L. braziliensis promastigote proteins associated with MPL adjuvant (LBMPL group). Ninety days after the therapeutics protocol, the dogs were euthanized and the spleen was collected for the proposed evaluations. Our results demonstrated a reduction of hyperplasia of red pulp and follicular area of white pulp, increased mRNA expression of IFN-γ, TNF-α, IL-12 and iNOS, and decreased IL-10 and TGF-β1, and intense reduction of splenic parasitism in dogs treated with the LBMPL vaccine. These results possibly suggest that the pro-inflammatory environment promoted the progressive organization of the splenic architecture favoring the cellular activation, with consequent parasite control. Along with previously obtained data, our results propose the LBMPL vaccine as a possible treatment strategy for canine visceral leishmaniasis (CVL).

Background: Scientific evidence indicates that biological complications in dental implants tend to be concentrated in a subset of individuals, which seems to imply that the host response may play a determining role in implant success. Over the last few decades, several polymorphisms have been studied. Polymorphisms in the interleukin (IL) 1 gene cluster have been associated with periodontitis. There are some similar features in the sequence of immunopathological events in peri-implant and periodontal infections. We aimed to investigate if individuals carrying the genetic single nucleotide polymorphism (SNP) in the IL-1A (rs1800587) and IL-1B (rs1143634) genes are more susceptible to develop peri-implantitis., Methods: A cross-sectional analytic pilot study was conducted in 20 Caucasian Portuguese subjects divided into two groups: 10 subjects with peri-implantitis and 10 subjects with peri-implant health (control group). Samples containing cells from the buccal mucosa were stored at -20 °C and later submitted to the DNA extraction process. Genetic analysis was performed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Data were analyzed by using descriptive and inferential statistical methodologies., Results: For the IL-1A (-889) gene polymorphism, it was observed that the mutated allele was present in a higher percentage in the peri-implantitis group compared to the control group (30% vs 15% respectively, Fisher's exact test, p  = 0.45). For the IL-1B (+3954) gene polymorphism, it was also observed that the altered allele was present in a higher percentage in the disease group compared to the control group (35% vs 10% respectively, Fisher's exact test, p  = 0.13). The positive genotype (at least one allele with nucleotide sequence changed in both genes) was detected in six patients, five belonging to the disease group and one to the health group., Conclusions: Regarding IL-1 gene polymorphisms, there was no statistically significant difference between the health and disease group, however a trend should be highlighted, showing a potential link between the IL-1 genotype and peri-implantitis. More studies are needed to clarify the role of genetic polymorphisms in the development of peri-implantitis., Competing Interests: The authors declare there are no competing interests., (©2022 Cardoso et al.)

Background: Value-Based Health Care (VBHC) is an evolving model of healthcare delivery aimed at achieving better patient outcomes at lower costs to the healthcare provider. The practise of VBHC requires efficient information systems with good reporting capability and subsequent outcome measuring . Information systems within the National Health Service (NHS) are often multiple and not necessarily integrated to one another. We therefore developed a systematic approach to collecting, validating and analysing data from multiple sources and information systems, with the aim of designing and endorsing an automatic system to capture health outcomes data in heart failure to support future VBHC models., Methods: A retrospective cohort of heart failure patients with reduced ejection fraction undergoing Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) procedures within a limited geographical area in South London were evaluated. A purpose built database was created to integrate, transform and validate health care data from multiple information systems., Results: Validation analysis shows that our implemented methodology has produced a robust dataset. Our limited cohort of 134 patients does not allow for any complex statistical analysis however has identified some important themes related to outcomes and costs., Conclusion: We have created a validated database specific to our Trust that can be upscaled locally with ease and transferred to other health diseases. Due to variations in local procedure from one Trust to another, this methodology now requires implementation across multiple sites to understand differences in transformation of data and outcome measuring.

Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the majority of patients develop incapacitating and persistent arthritis/arthralgia. Mayaro fever is a neglected and underreported disease without treatment or vaccine, which has gained attention in recent years after the competence of Aedes aegypti to transmit MAYV was observed in the laboratory, coupled with the fact that cases are being increasingly reported outside of endemic forest areas, calling attention to the potential of an urban cycle arising in the near future. Thus, to mitigate the lack of information about the pathological aspects of MAYV, we previously described the involvement of oxidative stress in MAYV infection in cultured cells and in a non-lethal mouse model. Additionally, we showed that silymarin, a natural compound, attenuated MAYV-induced oxidative stress and inhibited MAYV replication in cells. The antioxidant and anti-MAYV effects prompted us to determine whether silymarin could also reduce oxidative stress and MAYV replication after infection in an immunocompetent animal model. We show that infected mice exhibited reduced weight gain, hepatomegaly, splenomegaly, anaemia, thrombocytopenia, leukopenia, increased liver transaminases, increased pro-inflammatory cytokines and liver inflammation, increased oxidative damage biomarkers, and reduced antioxidant enzyme activity. However, in animals infected and treated with silymarin, all these parameters were reversed or significantly improved, and the detection of viral load in the liver, spleen, brain, thigh muscle, and footpad was significantly reduced. This work reinforces the potent hepatoprotective, antioxidant, anti-inflammatory, and antiviral effects of silymarin against MAYV infection, demonstrating its potential against Mayaro fever disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An important strategy to reduce the risk of visceral leishmaniasis (VL) in humans is to control the infection and disease progression in dogs, the domestic reservoir of Leishmania infantum parasites. Certain therapeutic strategies that modulate the host immune response show great potential for the treatment of experimental VL, restoring the impaired effector functions or decreasing host excessive responses. It is known that the overproduction of interleukin-10 (IL-10) promotes parasite replication and disease progression in human VL as well as in canine visceral leishmaniasis (CVL). Thus, in the present study we investigated the potential of the anti-canine IL-10 receptor-blocking monoclonal antibody (Bloq IL-10R) to control and reduce in vitro infectivity of L. infantum and improve the ability of PBMC isolated from VL dogs to alter the lymphoproliferative response and intracytoplasmic cytokines. Overall, GFP + Leishmania showed lower capacity of in vitro infectivity in the presence of Bloq IL-10R. Moreover, addition of Bloq IL-10R in cultured PBMC enhanced T-CD4 and CD8 proliferative response and altered the intracytoplasmic cytokine synthesis, reducing CD4 + IL-4 + cells and increasing CD8 + IFN-γ + cells after specific antigen stimulation in PBMC of dogs. Furthermore, we observed an increase of TNF-α levels in supernatant of cultured PBMC under IL-10R neutralizing conditions. Together, our findings are encouraging and reaffirm an important factor that could influence the effectiveness of immune modulation in dogs with VL and suggest that blocking IL-10R activity has the potential to be a useful approach to CVL treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Radiologists, and doctors in general, need relevant information for the quantification and characterization of pulmonary structures damaged by severe diseases, such as the Coronavirus disease 2019 (COVID-19). Texture-based analysis in scope of other pulmonary diseases has been used to screen, monitor, and provide valuable information for several kinds of diagnoses. To differentiate COVID-19 patients from healthy subjects and patients with other pulmonary diseases is crucial. Our goal is to quantify lung modifications in two pulmonary pathologies: COVID-19 and idiopathic pulmonary fibrosis (IPF). For this purpose, we propose the use of a three-dimensional multiscale fuzzy entropy (MFE3D) algorithm. The three groups tested (COVID-19 patients, IPF, and healthy subjects) were found to be statistically different for 9 scale factors ( p < 0.01 ). A complexity index (CI) based on the sum of entropy values is used to classify healthy subjects and COVID-19 patients showing an accuracy of 89.6 % , a sensitivity of 96.1 % , and a specificity of 76.9 % . Moreover, 4 different machine-learning models were also used to classify the same COVID-19 dataset for comparison purposes., (© 2021 Elsevier Ltd. All rights reserved.)

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, severe, and progressive lung disease with short life expectancy. Based on information theory and entropy measurement, a three-dimensional multiscale fuzzy entropy (MFE 3D ) algorithm is proposed to identify IPF patients from their computed tomography (CT) volumetric data. First, the validation of the algorithm was performed by analyzing several volumetric synthetic noises (white, blue, brown, and pink), MIX(p) processes-based volumes, and texture-based volumes. The entropy values obtained by MFE 3D were consistent with the values obtained using the one, and two-dimensional versions, validating its use in biomedical data. Hence, MFE 3D was applied to CT scans to identify the existence of IPF within two different groups, one of healthy subjects (26) and another of IPF patients (26). Statistical differences were found (p < 0.05) between the entropy values of each group in 5 scale factors out of 10. These results demonstrate that MFE 3D could be an interesting metric to identify IPF in CT scans.

Leishmaniasis is one of the most important tropical neglected diseases according to the World Health Organization. Even after more than a century, we still have few drugs for the disease therapy and their great toxicity and side effects put in check the treatment control program around the world. Moreover, the emergence of strains resistant to conventional drugs, co-infections such as HIV/Leishmania spp., the small therapeutic arsenal (pentavalent antimonials, amphotericin B and formulations, and miltefosine), and the low investment for the discovery/development of new drugs force researchers and world health agencies to seek new strategies to combat and control this important neglected disease. In this context, the aim of this review is to summarize new advances and new strategies used on leishmaniasis therapy addressing alternative and innovative treatment paths such as physical and local/topical therapies, combination or multi-drug uses, immunomodulation, drug repurposing, and the nanotechnology-based drug delivery systems.Key points• The treatment of leishmaniasis is a challenge for global health agencies.• Toxicity, side effects, reduced therapeutic arsenal, and drug resistance are the main problems.• New strategies and recent advances on leishmaniasis treatment are urgent.• Immunomodulators, nanotechnology, and drug repurposing are the future of leishmaniasis treatment.

Purpose: Sustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools., Methods: As manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases., Results: The U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos., Conclusions: The results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.

We report the successful clinical case of a patient scheduled for lumbar spine surgery in which we performed a bilateral single-shot erector spinae plane block as part of a multimodal analgesic strategy for pain control. Performing the block preoperatively dismissed the need for extra intraoperative opioids other than those for intubation, and enabled the use of paracetamol for analgesia only. Further, there was no need for hypotensive techniques, as the block provided satisfactory sympathetic blockade and regional vasodilation with a clear surgical field. Postoperatively, the patient had minor opioid consumption and was able to freely move without any motor impairment or pain from early on in the Post Anaesthesia Care Unit. The use of single-shot erector spinae plane block at the lumbar level for lumbar spine surgery analgesia emphasises its wide application and analgesic efficacy., (Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Quadratus lumborum block was first described in 2007 and currently there are descriptions of its achievement through four different injection points. This blockage provides abdominal wall and visceral analgesia, and one of its mechanisms is the dispersion of the local anesthetic into the paravertebral space. We describe the performance of a continuous quadratus lumborum type II block for postoperative analgesia in a partial nephrectomy., Case Report: A 64-year-old woman, scheduled for partial left laparoscopic nephrectomy. During the procedure, due to technical difficulties, an incision was made in the left flank to facilitate the surgical approach. In the early postoperative period, a continuous quadratus lumborum type II block was performed using ultrasonography as part of the multimodal analgesic strategy. Initially, 20ml of 0.2% ropivacaine was administered and 3cm of catheter were introduced into the interfascial space. Subsequently, a continuous infusion of 5.2mL.h -1 of 0.2% ropivacaine was given for 48hours. In the first 24 postoperative hours, the patient reported no pain at rest or on movement. In the following 24hours, she was free of pain at rest and only a slight pain (2/10) on movement., Conclusions: Continuous quadratus lumborum type II block was an effective postoperative analgesic option. Blocking of somatic nerves and visceral afferent pathways provided abdominal and visceral wall analgesia, allowing the reduction of opioid consumption. We consider relevant to explore the analgesic capacity of the quadratus lumborum block and its different approaches, as well as the possibility of it becoming an alternative in patients scheduled for kidney surgery., (Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: The superior gluteal nerve is responsible for innervating the gluteus medius, gluteus minimus and tensor fascia latae muscles, all of which can be injured during surgical procedures. We describe an ultrasound-guided approach to block the superior gluteal nerve which allowed us to provide efficient analgesia and anesthesia for two orthopedic procedures, in a patient who had significant risk factors for neuraxial techniques and deep peripheral nerve blocks., Clinical Report: An 84-year-old female whose regular use of clopidogrel contraindicated neuraxial techniques or deep peripheral nerve blocks presented for urgent bipolar hemiarthroplasty in our hospital. Taking into consideration the surgical approach chosen by the orthopedic team, we set to use a combination of general anesthesia and superficial peripheral nerve blocks (femoral, lateral cutaneous of thigh and superior gluteal nerve) for the procedure. A month and a half post-discharge the patient was re-admitted for debriding and correction of suture dehiscence; we performed the same blocks and light sedation. She remained comfortable in both cases, and reported no pain in the post-operative period., Conclusions: Deep understanding of anatomy and innervation empowers anesthesiologists to solve potentially complex cases with safer, albeit creative, approaches. The relevance of this block in this case arises from its innervation of the gluteus medius muscle and posterolateral portion of the hip joint. To the best of our knowledge, this is the first report of an ultrasound-guided superior gluteal nerve block with an analgesic and anesthetic goal, which was successfully achieved., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication., Clinical Reports: We report two cases in which we performed a quadratus lumborum type II block and general anesthesia for total gastrectomy and right hemicolectomy. There were no noteworthy events while performing the block and inducing general anesthesia, but within 30-40min serious hypotension and tachycardia were noted. As other motives for hypotension were ruled out, the event was interpreted as block-induced sympatholysis due to cephalad dispersion of the local anesthetic to the paravertebral and epidural space, and successfully managed with ephedrine and increase of the crystalloid infusion rate., Conclusions: The quadratus Lumborum block is safe to execute and provides effective abdominal wall and visceral analgesia. However, the possibility of eliciting undesired episodes should prompt caution when performing this block and practitioners should thereafter remain vigilant. Questions regarding ideal dosing, volumes, timing of block and pertinence of catheters remain to be answered., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

This article aims to reflect on communication and health projects and strategies involved in the struggle for the right to health, construction and defense of the Unified Health System. Drawing on studies, debates and deliberations that have been ongoing since the 8th National Health Conference and based on contemporary communication configurations, it problematizes tensions, challenges and opportunities related to digital culture, journalistic coverage and public communication in health institutions in Brazil.

Introduction and Objectives: Quadratus Lumborum block was recently described and has already shown good results as an analgesic technique in abdominal surgeries, having the potential to significantly reduce opioids consumption and be a valid alternative to epidural catheter. We performed a type II Quadratus Lumborum block for analgesia in a septic patient having a sub-total gastrectomy., Case Report: An 80 year-old, ASA III, male patient, weighting 50kg, with a history of arterial hypertension and hypercholesterolemia, diagnosed with sepsis due to purulent peritonitis was submitted to an open laparotomy. Bilateral ultrasound-guided type II Quadratus Lumborum block was performed before surgery, using 10mL of levobupivacaine 0.25% and 5mL of mepivacaine 1%, per side. Pain relief was achieved 5minutes after injection and the patient referred no pain in the immediate postoperative period., Discussion: Type II Quadratus Lumborum block may be considered a valid alternative for postoperative analgesia in a septic patient undergoing major abdominal surgery with some relative contraindications to epidural catheter placement. It allowed us to achieve excellent pain management avoiding opioids usage. However, more reports are still needed to properly access its usefulness., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Introduction: The development of new surgical techniques and medical devices, like therapeutical multimodal approaches has allowed for better outcomes on patients with rectal cancer (RCa). Owing to that, an increased awareness and investment towards better outcomes regarding patients' sexual and urinary function has been recently observed., Aim: Evaluate and characterize the sexual dysfunction of patients submitted to surgical treatment for RCa., Materials and Methods: An observational retrospective study including all male patients who underwent a surgical treatment for RCa between January 2011 December 2014 (n=43) was performed, complemented with an inquiry questionnaire to every patient about its sexual habits and level of function before and after surgery., Discussion: All patients were male, with an average of 64yo. (range 42-83yo.). The surgical procedure was a rectum anterior resection (RAR) in 22 patients (56%) and an abdominoperineal resection (APR) in 19(44%). Sixty three percent described their sexual life as important/very important. Sexual function worsening was observed in 76% (65% with complains on erectile function, and 27% on ejaculation). Fourteen patients (38%) didn't resume sexual activity after surgery. Increased age (p=0.007), surgery performed (APR) (p=0.03) and the presence of a stoma (p=0.03) were predictors of ED after surgery. A secondary analysis found that the type of surgery (APR) (p=0.04), lower third tumor's location (p=0.03) and presence of comorbidities (p=0.013) (namely, smokers and diabetic patients) were predictors of de novo ED after surgery., Conclusions: This study demonstrated the clear negative impact in sexual function of patients submitted to a surgical treatment for RCa. Since it is a valued feature for patients, it becomes essential to correctly evaluate/identify these cases in order to offer an adequate therapeutical option., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: Maintaining endotracheal tube patency is critical for neonates receiving mechanical ventilation. Endotracheal tube suctioning removes accumulated secretions preventing potential adverse events, however is also potentially hazardous to the patient., Objective: To compare respiratory rate, arterial blood oxygen saturation, heart rate and pain in newborns undergoing endotracheal tube suctioning with closed (CS) and open (OS) systems., Methods: Randomized crossover trial with 13 newborns from two Brazilian hospitals. The respiratory rate, arterial blood oxygen saturation, heart rate and pain (Premature Infant Pain Profile) were analysed: immediately before (T1), during (T2), immediately after (T3), 10 min after (T4) and 30 min (T5) after endotracheal suctioning., Results: The majority (11/85·0%) of the newborns were premature and 45% weighed less than 1000 g. No statistically significant difference was identified according to the use of CS or OS to all the parameters investigated. The main results demonstrated that in T2 arterial blood oxygen saturation was higher with CS (CS 93·0%; OS 89 · 0%; p = 0·561). In T3 there was an increase in respiratory rate average only with the use of OS (T1 50·0; T3 56·0). The pain score in T2 and heart rate in T3 were higher with OS without significant differences (p = 0·114; p = 0·479, respectively)., Conclusion: There was no significant difference in the studied clinical parameters or presence and intensity of pain according to the two investigated techniques of endotracheal tube suctioning., Relevance to Clinical Practice: This research can provide support for clinical practice regarding endotracheal tube suctioning of newborns describing that the use of closed systems was similar to the open system regarding pain presence and intensity, as well as, in the clinical effects analysed, in accordance with other studies produced in this field., (© 2015 British Association of Critical Care Nurses.)

Background and Objectives: Postdural puncture headache (PDPH) is a common complication following subarachnoid blockade and its incidence varies with the size of the needle used and the needle design. Supportive therapy is the usual initial approach. Epidural blood patch (EBP) is the gold-standard when supportive therapy fails but has significant risks associated. Sphenopalatine ganglion block (SPGB) may be a safer alternative., Case Report: We observed a 41 year-old female patient presenting with PDPH after a subarachnoid blockade a week before. We administrated 1l of crystalloids, Dexamethasone 4mg, parecoxib 40mg, acetaminophen 1g and caffeine 500mg without significant relief after 2hours. We performed a bilateral SPGB with a cotton-tipped applicator saturated with 0.5% Levobupivacaine under standard ASA monitoring. Symptoms relief was reported 5minutes after the block. The patient was monitored for an hour after which she was discharged and prescribed acetaminophen 1g and ibuprofen 400mg every 8hours for the following 2 days. She was contacted on the next day and again after a week reporting no pain in both situations., Conclusions: SPGB may attenuate cerebral vasodilation induced by parasympathetic stimulation transmitted through neurons that have synapses in the sphenopalatine ganglion. This would be in agreement with the Monro-Kellie concept and would explain why caffeine and sumatriptan can have some effect in the treatment of PDPH. Apparently, SPGB has a faster onset than EBP with better safety profile. We suggest that patients presenting with PDPH should be considered primarily for SPGB. Patients may have a rescue EBP if needed., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquid-liquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 μg/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 μg/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease., (Copyright © 2017 American Society for Microbiology.)

We report on a search for electronic recoil event rate modulation signatures in the XENON100 data accumulated over a period of 4 yr, from January 2010 to January 2014. A profile likelihood method, which incorporates the stability of the XENON100 detector and the known electronic recoil background model, is used to quantify the significance of periodicity in the time distribution of events. There is a weak modulation signature at a period of 431&#95;{-14}^{+16} day in the low energy region of (2.0-5.8) keV in the single scatter event sample, with a global significance of 1.9σ; however, no other more significant modulation is observed. The significance of an annual modulation signature drops from 2.8σ, from a previous analysis of a subset of this data, to 1.8σ with all data combined. Single scatter events in the low energy region are thus used to exclude the DAMA/LIBRA annual modulation as being due to dark matter electron interactions via axial vector coupling at 5.7σ.

Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum . Sixteen dogs received immunotherapy with MPL adjuvant ( n  = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n  = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in an ex vivo analysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3 + T lymphocytes and their subpopulations (TCD4 + and TCD8 + ), reduction of CD21 + B lymphocytes, increased NK cells (CD5 - CD16 + ) and CD14 + monocytes. Under in vitro conditions, the animals developed a strong antigen-specific lymphoproliferation mainly by TCD4 + and TCD8 + cells; increasing in both TCD4 + IFN-γ + and TCD8 + IFN-γ + as well as reduction of TCD4 + IL-4 + and TCD8 + IL-4 + lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL animals compared with MPL group. The skin tissue showed a reduction in parasite burden in LBMPL dogs 127.5 times higher than MPL. As expected, with skin parasite reduction promoted by immunotherapy, we observed a blocking transmission to sand flies in LBMPL dogs with only three positive dogs after xenodiagnosis. The results obtained in this study highlighted the strong potential for the use of this heterologous vaccine therapy as an important strategy for VL treatment.

The pinewood nematode, Bursaphelenchus xylophilus, recognized as a worldwide major forest pest, is a migratory endoparasitic nematode with capacity to feed on pine tissues and also on fungi colonizing the trees. Bursaphelenchus mucronatus, the closest related species, differs from B. xylophilus on its pathogenicity, making this nematode a good candidate for comparative analyses. Secretome profiles of B. xylophilus and B. mucronatus were obtained and proteomic differences were evaluated by quantitative SWATH-MS. From the 681 proteins initially identified, 422 were quantified and compared between B. xylophilus and B. mucronatus secretomes and from these, 243 proteins were found differentially regulated: 158 and 85 proteins were increased in B. xylophilus and B. mucronatus secretomes, respectively. While increased proteins in B. xylophilus secretome revealed a strong enrichment in proteins with peptidase activity, the increased proteins in B. mucronatus secretome were mainly related to oxidative stress responses. The changes in peptidases were evaluated at the transcription level by RT-qPCR, revealing a correlation between the mRNA levels of four cysteine peptidases with secretion levels. The analysis presented expands our knowledge about molecular basis of B. xylophilus and B. mucronatus hosts interaction and supports the hypothesis of a key role of secreted peptidases in B. xylophilus pathogenicity.

The deuteron is the simplest compound nucleus, composed of one proton and one neutron. Deuteron properties such as the root-mean-square charge radius rd and the polarizability serve as important benchmarks for understanding the nuclear forces and structure. Muonic deuterium μd is the exotic atom formed by a deuteron and a negative muon μ(-). We measured three 2S-2P transitions in μd and obtain r(d) = 2.12562(78) fm, which is 2.7 times more accurate but 7.5σ smaller than the CODATA-2010 value r(d) = 2.1424(21) fm. The μd value is also 3.5σ smaller than the r(d) value from electronic deuterium spectroscopy. The smaller r(d), when combined with the electronic isotope shift, yields a "small" proton radius r(p), similar to the one from muonic hydrogen, amplifying the proton radius puzzle., (Copyright © 2016, American Association for the Advancement of Science.)

Survival following very preterm birth is associated with cognitive and behavioral sequelae, which may have identifiable neural correlates. Many survivors of modern neonatal care in the 1990s are now young adults and the evolution of MRI findings into adult life has rarely been evaluated. We have investigated a cohort of 19-year-old adolescents without severe impairments born between 22 and 26weeks of gestation in 1995 (extremely preterm: EP). Using T2 data derived from magnetic resonance imaging we investigate differences between the brains of 46 EP participants (n=46) and the brains of a group of term-born controls (n=20). Despite EP adolescents having significantly reduced gray and white matter volumes, the composition of these tissues, assessed by both single and multi-component relaxometry, appears to be unrelated to either preterm status or gender. This may represent either insensitivity of the imaging technique or reflect that there are only subtle differences between EP subjects and their term-born peers., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Five new silver camphorimine complexes of general formula [Ag(NO3)(Y)L] were synthesized and fully characterized using spectroscopic and analytical techniques. The structure of [Ag(NO3)(OC10H14NC6H4NC10H14O)] () was analyzed using single crystal X-ray diffraction, showing that it arranges as a coordination polymer formed by sequential Ag(NO3) units bridged by the bi-camphor ligand (). The antimicrobial properties of the new complexes were screened using the disk diffusion method and their Minimal Inhibitory Concentrations (MIC) were assessed against selected bacterial strains of the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli, Pseudomonas aeruginosa, and Burkholderia contaminans. The lowest MICs were observed for , with estimated values of 72, 20, 32 and 19 μg mL(-1) for S. aureus, E. coli, B. contaminans, and P. aeruginosa, respectively. In the case of S. aureus, similar MIC values were obtained for silver nitrate and compound . All five compounds were bactericidal when used in concentrations equal or above the MIC value, as found by enumerating the total colony forming units (CFUs) after incubation in their presence.

Background: Leishmaniasis remains among the most important parasitic diseases in the developing world and visceral leishmaniasis (VL) is the most fatal. The hamster Mesocricetus auratus is a susceptible model for the characterization of the disease, since infection of hamsters with L. infantum reproduces the clinical and pathological features of human VL. In this context, it provides a unique opportunity to study VL in its active form. The main goal of this study was to evaluate the clinical, biochemical, and hematological changes in male hamsters infected through different routes and strains of L. infantum., Methods: In the current study, hamsters (Mesocricetus auratus) were infected with the L. infantum strains (WHO/MHOM/BR/74/PP75 and MCAN/BR/2008/OP46) by intradermal, intraperitoneal and intracardiac routes. The animals were monitored for a nine month follow-up period., Results: The hamsters showed clinical signs similar to those observed in classical canine and human symptomatic VL, including splenomegaly, severe weight loss, anemia, and leucopenia. Therefore the OP46 strain was more infective, clinical signs were more frequent and more exacerbated in IC group with 80 to 100 % of the animals showing splenomegaly, in the last month infection. Additionally, desquamation, hair loss and external mucocutaneous lesions and ulcers localized in the snout, accompanied by swelling of the paws in all animals, were observed. Consequently, the animals presented severe weight loss/cachexia, hunched posture, an inability to eat or drink, and non-responsiveness to external stimuli. Furthermore, regardless of strain, route of inoculum and time assessed, the animals showed renal and hepatic alterations, with increased serum levels of urea and creatinine as well as elevated serum levels of aspartate aminotransferase and alanine aminotransferase., Conclusions: These results strongly suggest that the inoculation through the intracardiac route resulted in a higher severity among infections, especially in the sixth and ninth month after infection via intracardiac, exhibited clinical manifestations and biochemical/hematological findings similar to human visceral leishmaniasis. Therefore, we suggest that this route must be preferentially used in experimental infections for pathogenesis studies of VL in the hamster model.

The common bean (Phaseolus vulgaris L.) is the world's most important legume for human consumption. Anthracnose (ANT; Colletotrichum lindemuthianum) and angular leaf spot (ALS; Pseudocercospora griseola) are complex diseases that cause major yield losses in common bean. Depending on the cultivar and environmental conditions, anthracnose and angular leaf spot infections can reduce crop yield drastically. This study aimed to estimate linkage disequilibrium levels and identify quantitative resistance loci (QRL) controlling resistance to both ANT and ALS diseases of 180 accessions of common bean using genome-wide association analysis. A randomized complete block design with four replicates was performed for the ANT and ALS experiments, with four plants per genotype in each replicate. Association mapping analyses were performed for ANT and ALS using a mixed linear model approach implemented in TASSEL. A total of 17 and 11 significant statistically associations involving SSRs were detected for ANT and ALS resistance loci, respectively. Using SNPs, 21 and 17 significant statistically associations were obtained for ANT and angular ALS, respectively, providing more associations with this marker. The SSR-IAC167 and PvM95 markers, both located on chromosome Pv03, and the SNP scaffold00021&#95;89379, were associated with both diseases. The other markers were distributed across the entire common bean genome, with chromosomes Pv03 and Pv08 showing the greatest number of loci associated with ANT resistance. The chromosome Pv04 was the most saturated one, with six markers associated with ALS resistance. The telomeric region of this chromosome showed four markers located between approximately 2.5 Mb and 4.4 Mb. Our results demonstrate the great potential of genome-wide association studies to identify QRLs related to ANT and ALS in common bean. The results indicate a quantitative and complex inheritance pattern for both diseases in common bean. Our findings will contribute to more effective screening of elite germplasm to find resistance alleles for marker-assisted selection in breeding programs.

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an unbinned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1σ for all periods, suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8σ, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of weakly interacting massive particles to electrons is excluded at 4.8σ.

Because of the continuous introduction of germplasm from abroad, some collections have a high number of accessions, making it difficult to explore the genetic variability present in a germplasm bank for conservation and breeding purposes. Therefore, the aim of this study was to quantify and analyze the structure of genetic variability among 500 common bean accessions to construct a core collection. A total of 58 SSRs were used for this purpose. The polymorphism information content (PIC) in the 180 common bean accessions selected to compose the core collection ranged from 0.17 to 0.86, and the discriminatory power (DP) ranged from 0.21 to 0.90. The 500 accessions were clustered into 15 distinct groups and the 180 accessions into four distinct groups in the Structure analysis. According to analysis of molecular variance, the most divergent accessions comprised 97.2% of the observed genetic variability present within the base collection, confirming the efficiency of the selection criterion. The 180 selected accessions will be used for association mapping in future studies and could be potentially used by breeders to direct new crosses and generate elite cultivars that meet current and future global market needs.

Early cognitive deficits in Alzheimer's disease (AD) seem to be correlated to dysregulation of glutamate receptors evoked by amyloid-beta (Aβ) peptide. Aβ interference with the activity of N-methyl-d-aspartate receptors (NMDARs) may be a relevant factor for Aβ-induced mitochondrial toxicity and neuronal dysfunction. To evaluate the role of mitochondria in NMDARs activation mediated by Aβ, we followed in situ single-cell simultaneous measurement of cytosolic free Ca(2+)(Cai(2+)) and mitochondrial membrane potential in primary cortical neurons. Our results show that direct exposure to Aβ + NMDA largely increased Cai(2+) and induced immediate mitochondrial depolarization, compared with Aβ or NMDA alone. Mitochondrial depolarization induced by rotenone strongly inhibited the rise in Cai(2+) evoked by Aβ or NMDA, suggesting that mitochondria control Ca(2+) entry through NMDARs. However, incubation with rotenone did not preclude mitochondrial Ca(2+) (mitCa(2+)) retention in cells treated with Aβ. Aβ-induced Cai(2+) and mitCa(2+) rise were inhibited by ifenprodil, an antagonist of GluN2B-containing NMDARs. Exposure to Aβ + NMDA further evoked a higher mitCa(2+) retention, which was ameliorated in GluN2B(-/-) cortical neurons, largely implicating the involvement of this NMDAR subunit. Moreover, pharmacologic inhibition of endoplasmic reticulum (ER) inositol-1,4,5-triphosphate receptor (IP3R) and mitCa(2+) uniporter (MCU) evidenced that Aβ + NMDA-induced mitCa(2+) rise involves ER Ca(2+) release through IP3R and mitochondrial entry by the MCU. Altogether, data highlight mitCa(2+) dyshomeostasis and subsequent dysfunction as mechanisms relevant for early neuronal dysfunction in AD linked to Aβ-mediated GluN2B-composed NMDARs activation., (Copyright © 2015 Elsevier Inc. All rights reserved.)